Ebola

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Ebola, or Ebola hemorrhagic fever (Ebola HF) is a severe, often-fatal disease in humans and nonhuman primates (monkeys, gorillas, and chimpanzees) that has occasionally appeared in outbreaks since its initial recognition in 1976. It causes a high fever and symptoms throughout the body. Its most notorious feature is its ability to cause abrupt bleeding, both external and internal, which often results in death.

The disease is caused by infection with Ebola virus, named after a river in the Democratic Republic of the Congo (formerly Zaire) in Africa, where it was first recognized. The most recent outbreak occurred in March 2008 in Uganda.

Ebola virus is a member of the Filoviridae family of viruses. The other member of that family, Marburg virus, causes Marburg hemorrhagic fever.


Contents

Types

Ebola virus electron micrograph. Source: CDC.

Ebola hemorrhagic fever is one of the deadliest of a group of diseases called viral hemorrhagic fevers. They range in seriousness from relatively mild illnesses to severe and potentially fatal diseases. All forms of viral hemorrhagic fever begin with fever and muscle aches. Depending on the virus, the disease can get worse until the patient becomes very ill with breathing problems, hemorrhage (severe bleeding), kidney failure, and shock (inadequate blood supply to the body).

Viral hemorrhagic fevers are caused by viruses from four families: filoviruses, arenaviruses, flaviviruses, and bunyaviruses. The usual hosts for most of these viruses are rodents or arthropods (such as ticks and mosquitoes). In some cases, the natural host for the virus is not known.

The Ebola virus is one of two members of the Filoviridae family of RNA viruses (flavus means "yellow" and refers to yellow fever, the first major known disease caused by a flavivirus). There are four known subtypes of Ebola virus, and a fifth is suspected of being responsible in a recent outbreak. Three of the four have caused disease in humans: Ebola-Zaire, Ebola-Sudan, and Ebola-Ivory Coast. The fourth, Ebola-Reston, has caused disease in nonhuman primates, but not in humans. The most recently discovered type, the Bundibugyo strain, caused an outbreak in November 2007.

Ebola-Zaire

Ebola-Zaire, sometimes referred to as ZEBOV (for "Zaire strain of Ebola virus"), has caused repeated outbreaks in humans in the Central African countries of Gabon and Republic of Congo (a country sometimes known as Zaire). It is an extremely virulent strain, killing not only some 90% of its human victims[1] but also causing massive die-offs of gorillas and chimpanzees in the region.[2]

Ebola-Sudan

The Sudan strain of Ebola appeared at about the same time the Zaire strain did in 1976. It has a lower fatality rate at about 50%.[3]

Ebola-Ivory Coast

Ebola-Ivory Coast emerged in 1994 and 1995, killing many in the West African country of Ivory Coast. In 1995, scientists studying this particular set of cases discovered that they were due to this new subtype.[4][5]

Ebola-Reston

Ebola-Reston, named for the Virginia, U.S. city in which imported monkeys were discovered to be infected with the virus, seems to be the least virulent. It causes a less dangerous illness in its ape and monkey victims, and has infected humans who haven't become ill.[1][6]

Ebola-Bundibugyo

The strain of Ebola that caused a 2007 outbreak in the Bundibugyo district in Uganda is suspected to be of a new strain.[7][8]

Signs and Symptoms

For Ebola HF, the incubation period, which is the length of time between coming into contact with the virus and developing the disease, ranges from 2 to 21 days. The illness starts suddenly, with fever, headache, joint and muscle aches, sore throat, and weakness. These symptoms are followed by diarrhea, vomiting, and stomach pain. A rash, red eyes, hiccups and internal and external bleeding may be seen in some patients. Death occurs from shock due to blood loss.[9]

Researchers do not understand why some people are able to recover from Ebola HF and others are not. However, patients who die usually haven't developed a significant immune response to the virus at the time of death.

Causes

Ebola is a virus, which is spread during epidemics mostly by human-to-human contact. Developing Ebola depends on being in the geographic locale of an outbreak, as well as coming into contact with the virus.

Where is the Ebola virus found?

The exact origin, locations, and natural habitat (known as the "natural reservoir") of Ebola virus remain unknown. Researchers believe that virus is zoonotic (animal-borne) and is normally maintained in a native African animal host that doesn't get sick from carrying it. A similar host is probably associated with Ebola-Reston, which was isolated from infected cynomolgous monkeys that were imported to the United States and Italy from the Philippines. The virus is not known to be native to other continents, such as North America.

Recent work suggest that Ebola and a related virus, the Marburg virus, are present in fruit bats; these bats might be the reservoir for Ebola.[10][11]

Ebola has devastated gorilla populations in Gabon and Congo for the last several years; the infected apes are suffering an estimated 90%–95% mortality rate, and scientists fear they are being pushed to the brink of extinction.[12][13]

Diagnosis

Diagnosing Ebola HF in someone who has been infected only a few days is hard because early symptoms, such as red eyes and a skin rash, are nonspecific to the virus—they are seen in other patients with diseases that occur much more frequently, like malaria or typhoid fever. However, if a person has the group of symptoms described above, and infection with Ebola virus is suspected, the patient needs to be urgently put into isolation. Doctors who see patients they think have Ebola usually do not make this decision alone. Local and state health departments and the CDC are also involved because of the grave risk to public health.

Laboratory tests

Blood tests are the most important way to diagnose Ebola virus infections. Immune tests which detect parts of the virus or human antibodies against it, as well as DNA detection using polymerase chain reaction (PCR), and virus isolation and culture are all blood tests that can be used to diagnose a case of Ebola HF. These tests can be used within a few days after symptoms start. The tests can also be performed on people who have already died of the illness to confirm the cause of death. This is important for officials and doctors who need to contain outbreaks by preventing spread and isolating people who have come into contact with the deadly virus.

Treatment

There is no standard treatment for Ebola HF. Patients receive supportive therapy while their body fights the disease. This means balancing the patient's fluids and electrolytes, maintaining their oxygen status and blood pressure, and treating them for any complicating infections. Since Ebola is a tropical disease, treatment usually occurs in local hospitals. These institutions may be deprived of critical resources necessary to treat and contain the disease.

Surviving an Ebola infection appears to depend strongly on the body's mounting a particular immune response called cell-mediated immunity. This type of immunity depends not on antibodies but on the activation of cells that are specialized to fight off infection, such as T cells, macrophages and natural killer cells. In one study of patients infected withe Ebola-Sudan, the patients that survived tended to have a greater activity of those cells than the patients who died.[3]

Prevention

The prevention of Ebola HF in Africa is difficult. Because the identity and location of the natural reservoir of Ebola virus are unknown, there are few established methods of preventing the cases that occur at the start of outbreaks.

If cases of the disease do appear, social and economic conditions in the areas most affected by Ebola often favor the spread of an epidemic within hospitals and clinics. Therefore, health care providers must be able to recognize a case of Ebola HF if one appears. They must also be able to perform diagnostic tests and be ready to take practical viral hemorrhagic fever isolation precautions, or barrier nursing techniques. These techniques include the wearing of protective clothing, such as masks, gloves, gowns, and goggles; the use of infection-control measures, including complete equipment sterilization; and the isolation of Ebola HF patients from contact with unprotected persons. The aim of all of these techniques is to avoid all contact with the blood or secretions of any patient. If a patient with Ebola HF dies, direct contact with the body of the deceased patient must also be prevented.

Persons living in areas affected by Ebola hemorrhagic fever should observe the following measures to help avoid illness:

  • As with other infectious illnesses, one of the most important preventive practices is careful and frequent handwashing. Cleaning the hands often, using soap and water (or waterless alcohol-based hand rubs when soap is not available and hands are not visibly soiled), removes potentially infectious materials from skin and helps prevent the virus from spreading. Gloves, when worn, should be washed with soap and water before removal, and then the person should wash his or her hands.
  • Contact with dead animals, especially primates, must be avoided.
  • "Bushmeat” (wild animals, including primates, sold for consumption as food in local markets) should not be eaten.
  • To minimize the possibility of infection, barrier techniques should be used when in close contact with a person or animal suspected of having Ebola. These precautions include wearing protective gowns, gloves, and masks, in addition to eye protection (e.g., eye glasses) or a face shield. Sterilization and proper disposal of needles and equipment, and proper disposal of patients' excretions are also important to prevent the spread of infection.

Chances of Developing Ebola Hemorrhagic Fever

Confirmed cases of human Ebola HF have been reported in the Democratic Republic of the Congo, Gabon, Sudan, the Ivory Coast, Uganda, and the Republic of the Congo. An individual with blood test evidence of infection but showing no apparent illness has been reported in Liberia, and a laboratory worker in England became ill as a result of an accidental needle-stick. No case of the disease in humans has ever been reported in the United States. Ebola-Reston virus caused severe illness and death in monkeys imported to research facilities in the United States and Italy from the Philippines. During these outbreaks, several research workers became infected with the virus, but did not become ill.

Ebola HF typically appears in sporadic outbreaks, usually spread within a health-care setting (a situation known as amplification). Sporadic, isolated cases probably occur as well, but go unrecognized.

How Ebola is Spread

After the first patient in an outbreak is infected, the virus can be transmitted in several ways. People can be exposed to Ebola virus from direct contact with the blood and/or secretions of an infected person. Thus, the virus is often spread through families and friends because they come in close contact with such secretions when caring for infected persons. People can also be exposed to Ebola virus through contact with objects, such as needles, that have been contaminated with infected secretions.

Nosocomial transmission refers to the spread of a disease within a health-care setting, such as a clinic or hospital. It occurs frequently during Ebola HF outbreaks, and includes both types of transmission described above. In African health-care facilities, where supplies are short, doctors and nurses must often care for patients without using protective clothing, such as mask, gown, or gloves. Prior to the advent of the AIDS epidemic, re-using needles and syringes was common, and this also contributed to the spread of Ebola virus within a hospital. These implements weren't of a disposable type, and often weren't sterilized. Sometimes they were simply rinsed before reinsertion into multi-use vials of medicine. When needles or syringes become contaminated with virus and are then reused, numerous people can become infected.

Ebola-Reston appeared in a primate research facility in Virginia, where it may have been transmitted from monkey to monkey through the air. While all Ebola virus species can spread through airborne particles (aerosols) under research conditions, this type of spread has not been documented among humans in a real-world setting, such as a hospital or household.

Related Problems

In an age of terrorism and air travel, a disease this contagious that kills this quickly is of understandable concern. At a 2005 meeting of the Society for General Microbiology, Dr Anthony Sanchez of the CDC presented an overview of Ebola vaccine development.

According to Dr. Sanchez:

“The biothreat posed by Ebola virus cannot be overlooked. We are seeing more and more naturally occurring human outbreaks of this deadly disease. With worldwide air travel and tourism the virus can now be transported to and from remote regions of the world. And it has huge potential as a possible weapon of bioterrorism. We desperately need a protective vaccine”.

Clinical Trials

Several clinical trials are underway to test the safety and efficacy of a vaccine for Ebola. Check here for updated details.

Research

Recent discoveries

A vaccine against both Ebola and Marburg viruses developed by the U.S. Army was recently tested on nonhuman primates, and provided 100% protection: even when the animals were subjected to 1,000 times the lethal dose of virus, none got sick.[14] A group of Canadian researchers successfully tested another vaccine in primates in 2005.[15]

Future research

Scientists and researchers are faced with the challenges of finding ways to diagnose Ebola HF early and conducting ecological investigations of Ebola virus and its possible reservoir. In addition, one of the research goals is to monitor suspected geographic areas to determine the incidence of the disease. More extensive knowledge of the natural reservoir of Ebola virus and how the virus is spread must be acquired to prevent future outbreaks effectively.

Expected Outcome

Ebola HF has about a 50%–90% mortality rate.[16]

History

Ebola was first recognized in Zaire (Democratic Republic of the Congo) in 1976. A second outbreak occurred nearly simultaneously in southern Sudan.[17] The index case, or first patient to get sick, was treated with an injection of the antimalarial drug chloroquine, thus illustrating the unfortunate fact that early symptoms of Ebola can resemble malaria. Many people at the same hospital subsequently became ill.[18]

Table of Known Cases and Outbreaks of Ebola Hemorrhagic Fever, in Chronological Order (from CDC Special Pathogens Branch)

Year(s) Country Ebola subtype Reported no. of human cases Reported no. (%) of deaths among cases Situation
1976Zaire [Democratic Republic of the Congo (DRC)]Ebola-Zaire318280 (88) Occurred in Yambuku and surrounding area. Disease was spread by close personal contact and by use of contaminated needles and syringes in hospitals/clinics. This outbreak was the first recognition of the disease.[18]
1976SudanEbola-Sudan284151 (53) Occurred in Nzara, Maridi and the surrounding area. Disease was spread mainly through close personal contact within hospitals. Many medical care personnel were infected. [17]
1976EnglandEbola-Sudan10 (0) Laboratory infection by accidental stick of contaminated needle.[19]
1977ZaireEbola-Zaire11 (100) Noted retrospectively in the village of Tandala.[20]
1979SudanEbola-Sudan3422 (65) Occurred in Nzara. Recurrent outbreak at the same site as the 1976 Sudan epidemic.
1989USAEbola-Reston00 (0)Ebola-Reston virus was introduced into quarantine facilities in Virginia, Texas, and Pennsylvania by monkeys imported from the Philippines. Four humans developed antibodies to Ebola-Reston virus but did not become ill.
1990USAEbola-Reston00 (0)Ebola-Reston virus was introduced once again into quarantine facilities in Virginia, and Texas by monkeys imported from the Philippines. Four humans developed antibodies but did not get sick.
1989-1990PhilippinesEbola-Reston00 (0)High mortality among cynomolgus macaques in a primate facility responsible for exporting animals in the USA. Three workers in the animal facility with high Ebola antibody levels.
1992ItalyEbola-Reston00 (0)Ebola-Reston virus was introduced into quarantine facilities in Sienna by monkeys imported from the same export facility in the Philippines that was involved in the episodes in the United States. No humans were infected.
1994GabonEbola-Zaire5231 (60)Occurred in gold-mining camps deep in the rain forest. Initially thought to be yellow fever; identified as Ebola hemorrhagic fever in 1995.
1994Ivory CoastEbola-Ivory Coast10 (0)Scientist became ill after conducting an autopsy on a wild chimpanzee in the Tai Forest. The patient was treated in Switzerland.
1995DemocraticEbola-Zaire315250 (81)Occurred in Kikwit and surrounding area. Traced to index case-patient who worked in forest adjoining the city. Epidemic spread through families and hospitals.
Republic of
the Congo (formerly Zaire)
1996 (Jan - April)GabonEbola-Zaire3721 (57)Occurred in Mayibout area. A chimpanzee found dead in the forest was eaten by people hunting for food. Nineteen people who were involved in the butchery of the animal became ill; other cases occurred in family members.
1996 - 1997 (July - Jan)GabonEbola-Zaire6045 (74)Occurred in Booué area with transport of patients to Libreville. Index case-patient was a hunter who lived in a forest camp. Disease was spread by close contact with infected persons. A dead chimpanzee found in the forest at the time was determined to be infected.
1996South Africa Ebola-Zaire21 (50)A medical professional traveled from Gabon to Johannesburg, South Africa, after having treated Ebola virus-infected patients and thus having been exposed to the virus. He was hospitalized, and a nurse who took care of him became infected and died.
1996USAEbola-Reston00 (0)Ebola-Reston virus was introduced into a quarantine facility in Texas by monkeys imported from the Philippines. No human infections were identified.
1996PhilippinesEbola-Reston00 (0)Ebola-Reston virus was identified in a monkey export facility in the Philippines. No human infections were identified.
2000 - 2001 UgandaEbola-Sudan425224 (53)Occurred in Gulu, Masindi, and Mbarara districts of Uganda. The three most important risks associated with Ebola virus infection were attending funerals of Ebola hemorrhagic fever case-patients, having contact with case-patients in one's family, and providing medical care to Ebola patients without using adequate personal protective measures.
2001 - 2002 (Oct 01 - March 02) GabonEbola-Zaire6553 (82)Outbreak occurred over the border of Gabon and the Republic of the Congo.
2001 - 2002 (Oct 01 - March 02) Republic of Congo Ebola-Zaire5743 (75)Outbreak occurred over the border of Gabon and the Republic of the Congo. This was the first time that Ebola hemorrhagic fever was reported in the Republic of Congo.
2002 - 2003 (Dec 02 - April 03) Republic of Congo Ebola-Zaire143128 (89)Outbreak occured in the districts of Mbomo and Kéllé in Cuvette Ouest Departement.
2003 (Nov - Dec) Republic of Congo Ebola-Zaire3529 (83)Outbreak occured in Mbomo and Mbandza villages located in Mbomo district, Cuvette Ouest Departement.
2004SudanEbola-Sudan177 (41)Outbreak occured in Yambio county of southern Sudan. This outbreak was concurrent with an outbreak of measles in the same area, and several suspected EHF cases were later reclassified as measles cases.
2007Democratic Republic of CongoEbola-Zaire264187 (71) Outbreak occurred in Kasai Occidental Province. The outbreak was declared over November 20. Last confirmed case on October 4 and last death on October 10.
Dec 2007/ Jan 2008 UgandaEbola14937 (25) Outbreak occurred in Bundibugyo District in western Uganda. First reported occurrence of a new strain.

References

  1. 1.0 1.1 Takada A, Feldmann H, Ksiazek TG, Kawaoka Y. Antibody-dependent enhancement of Ebola virus infection. J Virol. 2003 Jul;77(13):7539-44. Abstract | Full Text
  2. Walsh PD, Biek R, Real LA. Wave-like spread of Ebola Zaire. PLoS Biol. 2005 Nov;3(11):e371. Epub 2005 Oct 25. Abstract | Full Text
  3. 3.0 3.1 Sanchez A, Lukwiya M, Bausch D et al. Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels. J Virol. 2004 Oct;78(19):10370-7. Abstract | Full Text
  4. Le Guenno B, Formenty P, Wyers M, Gounon P, Walker F, Boesch C. Isolation and partial characterisation of a new strain of Ebola virus. Lancet. 1995 May 20;345(8960):1271-4. Abstract
  5. Sanchez A, Trappier SG, Mahy BW, Peters CJ, Nichol ST. The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3602-7. Abstract | Full Text
  6. Miranda ME, Ksiazek TG, Retuya TJ et al. Epidemiology of Ebola (subtype Reston) virus in the Philippines, 1996. J Infect Dis. 1999 Feb;179 Suppl 1:S115-9. Abstract
  7. CDC. Ebola Outbreak in the District of Bundibugyo, Uganda
  8. Ryu A. New Ebola Strain Blamed for Killing 16 in Uganda. Voice of America News. November 30. 2007.
  9. Cohen J. Containing the threat--don't forget Ebola. PLoS Med. 2004 Dec;1(3):e59. Abstract | Full Text
  10. Leroy EM, Kumulungui B, Pourrut X et al. Fruit bats as reservoirs of Ebola virus. Nature. 2005;438:575–576. Full Text
  11. Towner JS, Pourrut X, Albariño CG et al. Marburg Virus Infection Detected in a Common African Bat. PLoS ONE 2007;2(8):e764. Abstract | Full Text
  12. Conservation. Scientists say Ebola has pushed western gorillas to the brink. Science. 2007 Sep 14;317(5844):1484. Abstract
  13. Bermejo M, Rodríguez-Teijeiro JD, Illera G et al. Ebola outbreak killed 5000 gorillas. Science. 2006 Dec 8;314(5805):1564. Abstract | Full Text
  14. Swenson DL, Wang D, Luo M et al. Vaccine to confer to nonhuman primates complete protection against multistrain Ebola and Marburg virus infections. Clin Vaccine Immunol. 2008 Mar;15(3):460-7. Epub 2008 Jan 23. Abstract
  15. Jones SM, Feldmann H, Ströher U et al. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med. 2005 Jul;11(7):786-90. Epub 2005 Jun 5. Abstract
  16. World Health Organization: Ebola haemorrhagic fever.
  17. 17.0 17.1 Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO/International Study Team. Bull World Health Organ. 1978;56:247-70. http://www.ncbi.nih.gov/pubmed/307455 Abstract] | PDF
  18. 18.0 18.1 Ebola haemorrhagic fever in Zaire, 1976. Report of a WHO/International Study Team. Bull World Health Organ. 1978;56:271-93. Abstract | PDF
  19. Emond RT, Evans B, Bowen ET, Lloyd G. A case of Ebola virus infection. Br Med J. 1977 Aug 27;2(6086):541-4. Abstract | Full Text
  20. Heymann DL, Weisfeld JS, Webb PA, Johnson KM, Cairns T, Berquist H. Ebola hemorrhagic fever: Tandala, Zaire, 1977-1978. J Infect Dis. 1980 Sep;142(3):372-6. Abstract | PDF

External Links

World Health Organization: Ebola haemorrhagic fever

Blaine Harden. "Dr. Matthew's Passion." New York Times. February 18, 2001.

Charting the Path of the Deadly Ebola Virus in Central Africa. PLoS Biology Vol. 3, No. 11, e403 doi:10.1371/journal.pbio.0030403.

National Geographic Wild Chronicles: Gorilla Ebola. YouTube.

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