Ebola

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Ebola

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

Primary Source Connection

BIBLIOGRAPHY

Introduction

Ebola is a type of hemorrhagic fever that is caused by four subtypes of a virus called the Ebola virus. The virus is one of two members of Filoviridae, a family of RNA viruses. The name of the virus comes from a river located in the Democratic Republic of the Congo, formerly called Zaire, where the virus was first discovered during an outbreak of the disease.

Ebola is a terrifying disease that can progress steadily towards death. The destruction of internal organs caused by the infecting virus produces a great deal of internal bleeding and can cause bleeding from various parts of the body such as the eyes, gums, and nose. The disease caused by Ebola-Zaire, the first of the four types of the virus yet discovered, is fatal over 90% of the time.

The progression from health to death within a few weeks for those unlucky enough to contract the infection is one terrifying aspect of Ebola. The other is, essentially, a fear of the unknown. Even though the disease has been known since the late 1980s, the origin of Ebola, its reservoir, and how the disease can be prevented are still largely mysterious. The main reason for this is the infrequency of outbreaks and the speed of their appearance and disappearance. The infection quickly spreads from person to person through a local population and, because of the high death rate, soon disappears after running out of new hosts to infect. This pattern has made the study of Ebola difficult.

It is thought that Ebola is transmitted to humans from a natural host by a vector. This route of transmission occurs in some other diseases. One example is malaria, which is transferred to a susceptible person from an infected animal or person via mosquitoes. Ebola may be naturally present in chimpanzees. At least two outbreaks of Ebola-Zaire were determined to be due to contact between humans and infected chimpanzees. However, it may be that chimpanzees are not the natural host, but are themselves infected by the virus, which is transmitted to them from another host. As discussed below, the natural host may be bats, although this has not been proven. Likewise, studies by the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC) have not yet identified the vector that carries the virus from that host to humans. What is clear from the ferocity of past outbreaks is that once someone has been infected with Ebola, the virus is easily transferred from person to person.

Disease History, Characteristics, and Transmission

As of 2007, four subtypes of Ebola virus have been identified. Three of the subtypes cause disease in humans. The four subtypes of Ebola are slightly different in the sequence of their genetic material and in the composition of the proteins that are present on their surfaces. Analysis of blood obtained from people infected by one of the four viral subtypes has revealed slightly different antibody patterns. (An antibody is a protein produced by the immune system in response to the presence of a specific protein, which is termed an antigen.) The four subtypes of virus may have originated from a single virus that mutated to create the four slightly different subtypes over time, but this hypothesis has not yet been confirmed.

The first Ebola virus to be discovered was Ebola-Zaire. It was isolated near the Ebola River in the Democratic Republic of the Congo during an outbreak in 1976. There were 318 reported cases. Of these, 280 people died, a mortality rate of 88%. Other known occurrences of Ebola due to Ebola-Zaire include:

Democratic Republic of the Congo, 1977 (one case, one death)
Gabon, 1994 (52 cases, 31 deaths)
Democratic Republic of the Congo, 1995 (315 cases, 250 deaths)
Gabon, January to April 1996 (37 cases, 21 deaths)
Gabon, July 1996 to January 1997 (60 cases, 45 deaths)
South Africa, 1996 (two cases, one death; the disease was contracted in the Democratic Republic of the Congo)
Gabon and the Democratic Republic of the Congo, October 2001 to March 2002 (53 cases, 53 deaths in the Gabon outbreak; 57 cases, 43 deaths in the Congo outbreak)
Democratic Republic of Congo, December 2002 to April 2003 (143 cases, 128 deaths)
Democratic Republic of Congo, 2003 (35 cases, 29 deaths).

WORDS TO KNOW

AMPLIFICATION: A process by which something is made larger, or the quantity increased.

ANTIBODY: Antibodies, or Y-shaped immunoglobulins, are proteins found in the blood that help to fight against foreign substances called antigens. Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of antibodies (each with a unique genetic sequence).

ANTIGEN: Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of antibodies (each with a unique genetic sequence).

ANTISENSE DRUG: An antisense drug binds to mRNA, thereby blocking gene activity. Some viruses have mRNA as their genetic material, so an antisense drug could inhibit their replication

BUSH MEAT: The meat of terrestrial wild and exotic animals, typically those that live in parts of Africa, Asia, and the Americas; also known as wild meat.

HEMORRHAGIC FEVER: A hemorrhagic fever is caused by viral infection and features a high fever and a high volume of (copious) bleeding. The bleeding is caused by the formation of tiny blood clots throughout the bloodstream. These blood clots—also called microthrombi—deplete platelets and fibrinogen in the bloodstream. When bleeding begins, the factors needed for the clotting of the blood are scarce. Thus, uncontrolled bleeding (hemorrhage) ensues.

HOST: Organism that serves as the habitat for a parasite, or possibly for a symbiont. A host may provide nutrition to the parasite or symbiont, or simply a place in which to live.

RESERVOIR: The animal or organism in which the virus or parasite normally resides.

VECTOR: Any agent, living or otherwise, that carries and transmits parasites and diseases. Also, an organism or chemical used to transport a gene into a new host cell.

The second type of Ebola virus to be discovered was Ebola-Sudan. It was discovered in 1976 during an outbreak that occurred in Sudan (284 cases, 151 deaths). Other outbreaks involving Ebola-Sudan include:

England, 1976 (one case; when a lab technician studying the virus accidentally contracted the virus from a needle puncture)
Sudan, 1979 (34 cases, 22 deaths)
Uganda, 2000–2001 (425 cases, 224 deaths)
Sudan, 2004 (17 cases, 7 deaths).

The third type of Ebola virus to be discovered was Ebola-Reston. Outbreaks of Ebola occurred simultaneously in 1989 in three animal facilities in the United States that had received monkeys imported from the Philippines. One of the facilities was in Reston, Virginia, and the virus took its name from the outbreak among the primates at this facility. No humans died in the outbreak, although four people were infected, as shown by the antibodies that they developed to the virus. This outbreak formed the basis for a bestselling book by Richard Preston called The Hot Zone and a motion picture called Outbreak Other outbreaks of Ebola-Reston in 1990, 1992, and 1996 involved deaths among other primates, but no human fatalities (although some people had produced antibodies to the virus). Thus far, Ebola-Reston has not caused human illness.

The final subtype of Ebola virus, as of 2007, is Ebola-Ivory Coast, which was discovered in 1994 in Ivory Coast. It caused one non-lethal case involving a scientist who contracted the infection after conducting an autopsy on a chimpanzee.

IN CONTEXT: DISEASE IN DEVELOPING NATIONS

As of May 2007, the natural reservoir of the Ebola virus remained unknown. The World Health Organization (WHO) states that “the natural reservoir of the Ebola virus is unknown despite extensive studies, but seems to reside in the rain forests on the African continent and in the Western Pacific.”

“Although non-human primates have been a source of infection for humans, they are not thought to be the reservoir. They, like humans, are argued to be infected directly from the natural reservoir or through a chain of transmission from the natural reservoir. On the African continent, Ebola infections of human cases have been linked to direct contact with gorillas, chimpanzees, monkeys, forest antelope and porcupines found dead in the rainforest. So far, the Ebola virus has been detected in the wild in carcasses of chimpanzees (in Côte-d'Ivoire and Republic of Congo), gorillas (Gabon and Republic of Congo) and duikers (Republic of Congo).”

“Because bats deliberated infected with Ebola do not die there is continued scientific speculation that bats or mammals may play a role in harboring the virus in the wild.”

SOURCE: World Health Organization

The various types of Ebola virus are all filoviruses. One characteristic of filoviruses is their long, stringlike shape. When observed using the high magnification power of the electron microscope, the viruses can be coiled, circular, U-shaped, or even shaped like a cane (or a shepherd's crook). The different shapes may not be natural, but rather may be formed artificially during purification of the virus.

The molecular details of the Ebola infection have been clarified. This work can only be done in a few laboratories in the world that are designed for research involving highly dangerous and infectious microorganisms. The infection begins when a protein on the surface of the virus recognizes a host molecule. It is not known whether the host molecule is another protein, lipid, or carbohydrate. Following the linkage between the viral protein and the host receptor, the viral genetic material enters the host cell. It is not known how this occurs. Increased understanding of these early steps is vital, since by blocking the viral attachment to the host cell and/or the transfer of the genetic material into the host cell, the subsequent infection could be stopped. Efforts to develop a vaccine are focusing on these steps. For example, blocking the adherence of a microbe to a host cell has proven successful in the development of a preliminary vaccine for cattle against a bacterium called Escherichia coli O157:H7, which can cause a lethal infection in humans, popularly known as “hamburger disease.”

Ebola viruses contain RNA. For the manufacture of a new virus, the infecting virus must use the host cell's genetic machinery to read the viral payload of RNA and to manufacture one of the viral proteins. Once this so-called nonstructural protein is made, it can decode the remaining viral genetic material to manufacture seven other proteins. These proteins are described as being structural— they are used to form the new virus. The new virus particles are eventually released from the host cell when the cell bursts, and another cycle of infection begins as new cells are infected. How the virus, with just eight proteins, manages to make new copies of itself and evade the attempts by the hosts’ immune system to stop the infection is unclear.

In their natural host, the Ebola virus presumably does not cause a serious infection. If it did, it would not persist, since the host would be killed. However, in humans the resulting infection can be devastating. Within days, Ebola-Zaire and Ebola-Sudan produce a high fever, headache, generalized muscle aches (myalgia), abdominal pain, tiredness, and diarrhea. Cells lining the intestinal tract and stomach can be damaged, causing bloody diarrhea and vomiting of blood. At this stage some people do recover. But, for many, the infection worsens. Massive internal bleeding sends a person into shock and can cause heart damage. Death soon follows.

One of the challenges of combating an Ebola outbreak is the fact that the early symptoms of the infection are similar to those of the flu, malaria, typhoid fever, and several bacterial infections, which occur more often and are not as serious. By the time the true nature of the infection becomes known, many people in a community could have been infected.

The swiftness of the infection has been noted by some authors. Others feel, however, that the two-week course of the infection is not unusually quick. The latter view is true when a patient is near medical care in a developed country. However, in rural regions of Africa where Ebola is most common, medical care may be days in coming and even then may not be capable of dealing with a severe infection. In that situation, even a disease that develops within a week is swift and serious.

In some Ebola outbreaks, the initial infection has been traced to contact between humans and an animal (usually a primate) that harbors the virus. However, it is still unclear whether the primate is the natural host or becomes infected through contact with another animal. What is now clear is that the contagious person-to-person transmission of the virus subsequently occurs via infected blood or body fluids. This transfer can occur directly, with someone coming into contract with blood or body fluids during handling and care of a patient. Accidental infection during study of the virus also has occurred.

The rapid spread of Ebola is also aided by the location of most of the outbreaks. The areas in Africa where Ebola appears are poor, rural, and do not have medical facilities close by. The health care facilities that are available are not likely to have space available to isolate the infected patient from other patients, which can contribute to the spread of the infection.

The pattern of the Ebola-Reston outbreak that occurred in Virginia in 1989 indicates that the virus may be capable of airborne spread. In that outbreak, at least one of the primates who became ill was never in contact or even in the same room as the other sick primates. Lab studies have demonstrated that aerosols of the virus can infect test animals. Whether this route plays a major role in Ebola is unclear, but the general feeling is that airborne transmission is not as important as transmission by body fluids.

IN CONTEXT: CULTURAL CONNECTIONS

Because the Ebola virus is transmitted by direct contact with the body fluids (blood, secretions, etc.) of infected persons, living or dead, various cultural practices can facilitate Ebola transmission. The World Health Organization (WHO) states “Burial ceremonies where mourners have direct contact with the body of the deceased person can play a significant role in the transmission of Ebola.”

WHO also reports that “the infection of human cases with Ebola virus has been documented through the handling of infected chimpanzees, gorillas, and forest antelopes—both dead and alive—as was documented in Côte d'Ivoire, the Republic of Congo and Gabon.”

SOURCE: World Health Organization

Scope and Distribution

Almost all confirmed cases of Ebola through 2007 have been in Africa. However, the infection may also occur in the Western Pacific because the Reston, Virginia, outbreaks were caused by monkeys imported from the Philippines.

The rapid deterioration of a person following the appearance of symptoms and the fact that the affected villages can be difficult to reach has meant that response to infections by disease control officials from organizations such as the WHO and the CDC occurs long after the disease has begun. This has made the discovery of Ebola's origin difficult. As of 2007, the source of the Ebola viruses is still unknown. The general agreement among scientists who study Ebola is that, because other filoviruses can infect African monkeys, macaques, and chimpanzees without causing harm to these hosts, the host for the Ebola viruses may be similar. However, Ebola does harm some primates. Furthermore, an intensive 12-year-long sampling of tens of thousands of amphibians, mammals, birds, reptiles, and insects failed to detect the viruses.

Bats have also been considered as Ebola's natural host. The people who first became ill in two of the outbreaks worked in buildings where bats lived and may have come into contact with the bats. Furthermore, in a study that deliberately introduced Ebola virus into a number of vertebrates, the virus persisted only in bats. More evidence supporting the involvement of bats was published in Nature in 2006. The study reported on a survey of over 1,000 animals from Gabon and Republic of the Congo, including over 650 bats. Of these, Ebola virus RNA was found in 13 fruit bats. Bats also can harbor several other viruses that are related to Ebola. This evidence for the involvement of bats as the natural host of Ebola is still circumstantial. To date, there is no evidence that an infected bat is capable of infecting another animal, such as a primate.

Treatment and Prevention

Currently, there is no cure for Ebola. Treatment consists of keeping the patient as comfortable and pain-free as possible and minimizing the spread of infection. Additional treatment measures include restoring lost fluids, trying to minimize bleeding, and dealing with any secondary infections that might occur.

As of 2007, prevention of Ebola is impossible, but research is underway on several fronts. Antisense drugs have been used successfully in a small number of infected Rhesus monkeys. Antisense therapy uses genetic material that is complimentary to the region of interest in the virus. Because the added stretch of genetic material is complimentary, it binds with the target region. This prevents the target region from being used in the viral replication process. Put another way, antisense drugs can shut down the infectious process. Whether this approach will prove successful as a prevention strategy for Ebola is unclear, and much research still remains to be done.

Vaccines are another preventative strategy that is being actively explored. In the case of Ebola, several other viruses have been engineered to contain one of the Ebola proteins that is present on the surface of the virus. This bioengineered virus is then administered to monkeys, and the monkeys produce antibodies to the Ebola surface protein. When an intact Ebola virus is given to the monkeys, the anti-Ebola antibody can block the attachment of the Ebola surface protein to the host cell. This approach has shown enough promise to warrant giving the vaccine to humans to see if they produce the anti-Ebola antibody. As of 2007, this vaccine is still being studied.

Impacts and Issues

Ebola affects people in the most basic way. It strikes with little warning and can sweep through a village in a short time. In the rural settings where the disease usually occurs, medical care is minimal and health care providers are stretched to their limits to contain the infection and provide basic comforts to those who are ill.

Though the best selling book The Hot Zone and the movie Outbreak were somewhat sensational, they address the lethality of Ebola. These popular depictions of Ebola served a useful purpose in making the average person more aware of Ebola specifically and infectious diseases in general.

Ebola is a striking example of how human encroachment on regions that were previously uninhabited can bring people into contact with microorganisms to which they had not been previously exposed. Another example of this phenomenon is the emergence of avian influenza in humans. Long a disease transferred between some species of poultry, closer human contact with poultry has enabled the avian flu virus to adapt so that it is capable of, initially, bird-to-human transmission and, within the past several years, human-to-human transmission.

In the case of Ebola, human encroachment on previously uninhabited areas includes increased contact with the natural host of the disease. The blurring of the boundaries between the human and the natural world has brought people into closer contact with primates, who are either the natural reservoir of the virus or who acquire the infection from the natural reservoir, possibly a fruit bat. The virus can spread to humans who kill and eat apes or chimpanzees. Bush meat, including the meat of primates, has long been eaten by rural Africans, and its sale is still an important part of the rural economy. In addition, bush meat has become increasingly popular as a delicacy in the western world.

The link between the consumption of bush meat and the spread of Ebola has spurred efforts to restrict poaching. A 2005 meeting involving 23 African nations and representatives of the United Nations addressed the problem of the declining great ape population and urged stricter controls on poaching and deforestation (which increases the access of people to ape territory). While admirable, the effectiveness of the campaign is debatable. Ape meat is still available for sale in many local markets in regions of Africa and is sought by buyers in western countries.

While some species may naturally harbor the Ebola virus without harm, other species are being decimated. Beginning in 2002, conservationists in some regions of Africa began to note a die-off of western gorillas and common chimpanzees. The great ape population in the African nation of Gabon has declined by half since the 1990s, with Ebola and poaching cited as the most likely causes. Without a concerted effort, these near-human creatures may become extinct within decades.

Part of the reason for the ferocity of an Ebola outbreak is a lack of understanding of the disease among those who are most affected by it. More education targeting those who are at risk of acquiring the infection is still needed. For example, burial customs in many African cultures include an open viewing of the deceased, which potentially exposes the mourners to the virus. This practice can amplify the spread of the virus—that is, the virus can affect more people than it otherwise would. Amplification is an important means by which a variety of viral and bacterial diseases can spread. In the case of Ebola and mourning customs, learning to pay respect to the deceased person without touching or even seeing them would help reduce the spread of Ebola.

During some initial outbreaks, well-meaning medical personnel helped spread the virus. The infection of health care workers is, unfortunately, a common aspect of Ebola outbreaks. The use of protective measures, such as masks and gloves, lessens the risk of passing the infection to caregivers. In some rural clinics, however, such measures—commonplace in medical clinics in developed countries—are a luxury.

Development of a vaccine is a primary goal of those concerned with the control of Ebola. In 2003, researchers at the Dale and Betty Bumpers Vaccine Research Center and the U.S. Army Medical Research Institute reported the development of a vaccine that protects monkeys from injected Ebola virus. The vaccine involves a two-stage process in which immunity results from the injection of non-infectious genetic material from the Ebola virus followed a few weeks later by the introduction of another virus that carries genes of the Ebola virus, which are vital to the establishment of an infection. The resulting immune response can stop the Ebola infection.

As of 2007, the DNA vaccine is still undergoing evaluation. Small-scale human trials have been done. However, one stumbling block in its development concerns the ethical issue of testing the vaccine in humans on the large scale required for approval processes, since this would involve exposing people to the virus. In addition, it is not clear whether a vaccine will work in people whose immune systems are not functioning normally. This is an important consideration, since Africa is also home to millions of people who suffer from acquired immunodeficiency syndrome (AIDS, also cited as acquired immune deficiency syndrome), a disease whose hallmark is the deterioration in immune system function.

Another issue concerning serious infections, including Ebola, is the potential of the microbe to be used as a weapon. Indeed, Ebola has been considered for development as a biological weapon by both the United States and Russia (then the Soviet Union). More recently, members of the Japanese cult Aum Shinrikyo—who released sarin gas in the Tokyo subway system in 1995, killing 12 people and injuring almost 1,000—visited Zaire in 1992. Under the guise of offering medical aid to victims of an Ebola outbreak, cult members instead tried to acquire some virus to use as a terrorist weapon.

Primary Source Connection

The following press release from the World Health Organization details its field response to a 2004 Ebola outbreak in southern Sudan. Along with mobilizing supplies and health workers, education of local villagers at the center of the outbreak was crucial in containing the spread of the disease.

WHO Announces End of Ebola Outbreak in Southern Sudan

Geneva—Today marks the 42nd day since the last person identified as infected with Ebola haemorrhagic fever died on 26 June 2004 in Yambio Hospital, southern Sudan. As 42 days is twice the maximum incubation period for Ebola, and as no further cases have been identified, WHO declares today that the outbreak in southern Sudan is over.

“The rapid containment of this outbreak was a tremendous success for the health authorities, WHO, and the international community involved in the control operations,” said Dr Abdullah Ahmed, head of WHO, southern Sudan, and coordinator of the response.

As of today, the health authorities of Yambio County have reported a total of 17 cases, including seven deaths from Ebola. Ebola haemorrhagic fever is a febrile illness which causes death in 50–90% of all clinically ill cases. It is transmitted by direct contact with the blood, secretions, organs or bodily fluids of infected persons.

“In Yambio, WHO and our partners were able to apply lessons learned during responses to the five Ebola outbreaks that have occurred since 2000,” said Dr. Pierre Formenty, who worked as part of WHO's response team. Ebola outbreaks have been detected more frequently in recent years, making local and international collaboration essential.

During this outbreak, Ebola virus (sub-type Sudan) was confirmed by laboratory tests at the Kenya Medical Research Institute and the Centers for Disease Control and Prevention in the United States. When the outbreak was first reported in late May, a response team including members from WHO southern Sudan Early Warning and Response Network (EWARN), and WHO headquarters was formed to work with local health authorities in creating a Crisis Committee to control the outbreak.

The committee included UNICEF, Médecins Sans Frontières-France and other non-governmental organizations and churches working in public health. The international response to the outbreak also included partners from WHO's Regional Office for the Eastern Mediterranean, the Global Outbreak Alert and Response Network (GOARN) as well as experts from the CDC, the European Programme for Intervention Epidemiology Training, Field Epidemiology Training Programme, Egypt and the Health Protection Agency in the United Kingdom.

Intensive social mobilization for Ebola was essential to the outbreak's containment. Key messages about the disease and behaviour-specific precautionary advice were passed on to the people in and around Yambio by local community advocates.

“Once the people of Yambio were convinced of the very real risks Ebola posed and they understood what they could do to protect themselves and their families the outbreak response was greatly accelerated,” said Ms. Asiya Odugleh from the WHO Mediterranean Centre for Vulnerability Reduction, Tunis, who assisted the county social mobilization team.

The control efforts included, for example, an isolation ward at Yambio Hospital with a low fence so that patients were effectively isolated, yet still able to see and talk to their family and friends over the fence at a safe distance. Such simple adaptations of disease control measures made it easier for families to accept the case management of patients in the isolation unit, while ensuring maximum protection for the medical team and patients.

“The lessons we learned in Yambio from this outbreak will strengthen our responses to future outbreaks,” said Dr. Hassan El Bushra from the WHO Regional Office for the Eastern Mediterranean in Cairo. The Yambio experience has proven the value of rapid outbreak detection, local response capacities, active community involvement, and the coordination of specialized international assistance to the outbreak's containment.

“WHO cannot predict where or when the next Ebola outbreak will happen,” said Dr. El Bushra, “But we can continue laying the groundwork by building on what we have learned in Yambio.”

World Health Organization. Epidemic and Pandemic Alert and Response.

WORLD HEALTH ORGANIZATION. “WHO ANNOUNCES END OF EBOLA OUTBREAK IN SOUTHERN SUDAN.” PRESS RELEASE, AUGUST 7, 2004. AVAILABLE ONLINE AT <HTTP://WWW.WHO.INT/CSR/DON/2004_08_07/EN/INDEX.HTML>