Ebola
Ebola, also known as Ebola virus disease and Ebola hemorrhagic fever, is a zoonotic viral hemorrhagic fever in humans and other primates, caused by four of the six known ebolaviruses. Symptoms typically start anywhere between two days and three weeks after infection. The first symptoms are usually fever, sore throat, muscle pain, and headaches. These are usually followed by vomiting, diarrhoea, rash, hepatic and renal dysfunction, at which point some people begin to bleed both internally and externally. The disease causes a mortality rate of anywhere between 25 and 90%, averaging out at approximately 50%. The viral species involved and timing of treatment play a critical role in its prognosis. Death is often due to shock from fluid loss, and typically occurs between 6 and 16 days after the first symptoms appear.
The viruses have caused intermittent outbeaks in Sub-Sahara Africa since 1976 when the disease was first reported, with the largest one being the 2014 Western African epidemic. They spread through direct contact with body fluids, such as blood from infected humans or other animals, or from contact with items that have recently been contaminated with infected body fluids. There have been no documented cases, either in nature or under laboratory conditions, of spread through the air between humans or other primates. After recovering from Ebola, semen or breast milk may continue to carry the virus for anywhere between several weeks to several months. Fruit bats are believed to be the natural host of the viruses; they are able to spread the viruses without being affected by it. The symptoms of Ebola may resemble those of several other diseases, including malaria, cholera, typhoid fever, meningitis and other viral hemorrhagic fevers. Diagnosis is confirmed by testing blood samples for the presence of viral RNA, viral antibodies or the virus itself.
Control of outbreaks requires coordinated medical services and community engagement, including rapid detection, contact tracing of those exposed, quick access to laboratory services, care for those infected, and proper disposal of the dead through cremation or burial. Prevention measures involve wearing proper protective clothing and washing hands when in close proximity to patients and while handling potentially infected bushmeat, as well as thoroughly cooking bushmeat. Two treatments are associated with improved outcomes. Early supportive care and treatment of symptoms increases the survival rate considerably compared to late start. These include oral rehydration therapy or giving intravenous fluids, and treating symptoms. An Ebola vaccine was approved by the US FDA in December 2019. In October 2020, atoltivimab/maftivimab/odesivimab was approved for medical use in the United States to treat the disease caused by Zaire ebolavirus.
Signs and symptoms
Onset
The length of time between exposure to the virus and the development of symptoms is between 2 and 21 days, and usually between 4 and 10 days. However, recent estimates based on mathematical models predict that around 5% of cases may take longer than 21 days to develop.Symptoms usually begin with a sudden influenza-like stage characterised by fatigue, fever, weakness, decreased appetite, muscular pain, joint pain, headache, and sore throat. The fever is usually higher than. This is often followed by nausea, vomiting, diarrhoea, abdominal pain, and sometimes hiccups. The combination of severe vomiting and diarrhoea often leads to severe dehydration. Next, shortness of breath and chest pain may occur, along with swelling, headaches, and confusion. In about half of the cases, the skin may develop a maculopapular rash, a flat red area covered with small bumps, five to seven days after symptoms begin.
Bleeding
In some cases, internal and external bleeding may occur. This typically begins five to seven days after the first symptoms. All infected people show some decreased blood clotting. Bleeding from mucous membranes or from sites of needle punctures has been reported in 40–50% of cases. This may cause vomiting blood, coughing up of blood, or blood in stool. Bleeding into the skin may create petechiae, purpura, ecchymoses or haematomas. Bleeding into the whites of the eyes may also occur. Heavy bleeding is uncommon; if it occurs, it is usually in the gastrointestinal tract. The incidence of bleeding into the gastrointestinal tract was reported to be ~58% in the 2001 outbreak in Gabon, but in the 2014–15 outbreak in the US it was ~18%, possibly due to improved prevention of disseminated intravascular coagulation.Recovery or death
Recovery may begin between seven and 14 days after first symptoms. Death, if it occurs, follows typically six to sixteen days from first symptoms and is often due to shock from fluid loss. In general, bleeding often indicates a worse outcome, and blood loss may result in death. People are often in a coma near the end of life.Those who survive often have ongoing muscular and joint pain, liver inflammation, and decreased hearing, and may have continued tiredness, continued weakness, decreased appetite, and difficulty returning to pre-illness weight. Problems with vision may develop. It is recommended that survivors wear condoms for at least twelve months after initial infection or until the semen of a male survivor tests negative for Ebolavirus on two separate occasions.
Survivors develop antibodies against Ebola that last at least 10 years, but it is unclear whether they are immune to additional infections.
Cause
EVD in humans is caused by four of six viruses of the genus Ebolavirus. The four are Bundibugyo virus, Sudan virus, Taï Forest virus and one simply called Ebola virus. EBOV, species Zaire ebolavirus, is the most dangerous of the known EVD-causing viruses, and is responsible for the largest number of outbreaks. The fifth and sixth viruses, Reston virus and Bombali virus, are not thought to cause disease in humans, but have caused disease in other primates. All six viruses are closely related to marburgviruses.Virology
Ebolaviruses contain single-stranded, non-infectious RNA genomes. Ebolavirus genomes contain seven genes including 3'-UTR-NP-''VP35-VP40-GP-VP30-VP24-L''-5'-UTR. The genomes of the five different ebolaviruses differ in sequence and the number and location of gene overlaps. As with all filoviruses, ebolavirus virions are filamentous particles that may appear in the shape of a shepherd's crook, of a "U" or of a "6," and they may be coiled, toroid or branched. In general, Ebola virions are 80 nanometers in width and may be as long as 14,000 nm.Their life cycle is thought to begin with a virion attaching to specific cell-surface receptors such as C-type lectins, DC-SIGN, or integrins, which is followed by fusion of the viral envelope with cellular membranes. The virions taken up by the cell then travel to acidic endosomes and lysosomes where the viral envelope glycoprotein GP is cleaved. This processing appears to allow the virus to bind to cellular proteins enabling it to fuse with internal cellular membranes and release the viral nucleocapsid. The Ebolavirus structural glycoprotein is responsible for the virus' ability to bind to and infect targeted cells. The viral RNA polymerase, encoded by the L gene, partially uncoats the nucleocapsid and transcribes the genes into positive-strand mRNAs, which are then translated into structural and nonstructural proteins. The most abundant protein produced is the nucleoprotein, whose concentration in the host cell determines when L switches from gene transcription to genome replication. Replication of the viral genome results in full-length, positive-strand antigenomes that are, in turn, transcribed into genome copies of negative-strand virus progeny. Newly synthesised structural proteins and genomes self-assemble and accumulate near the inside of the cell membrane. Virions bud off from the cell, gaining their envelopes from the cellular membrane from which they bud. The mature progeny particles then infect other cells to repeat the cycle. The genetics of the Ebola virus are difficult to study because of EBOV's virulent characteristics.
Initial case
Although it is not entirely clear how Ebola initially spreads from animals to humans, the spread is believed to involve direct contact with an infected wild animal or fruit bat. Besides bats, other wild animals that are sometimes infected with EBOV include several species of monkeys such as baboons, great apes, and duikers.Animals may become infected when they eat fruit partially eaten by bats carrying the virus. Fruit production, animal behavior and other factors may trigger outbreaks among animal populations.
Evidence indicates that both domestic dogs and pigs can also be infected with EBOV. Dogs do not appear to develop symptoms when they carry the virus, and pigs appear to be able to transmit the virus to at least some primates. Although some dogs in an area in which a human outbreak occurred had antibodies to EBOV, it is unclear whether they played a role in spreading the disease to people.
Areas undergoing deforestation are among the most likely places for outbreaks due to changes in the landscape bringing wildlife into closer contact with humans, including the West African Ebola virus epidemic. Index cases of EVD have often been close to recently deforested lands.
Reservoir
The natural reservoir for Ebola has yet to be confirmed; however, bats are considered to be the most likely candidate. Three types of fruit bats were found to possibly carry the virus without getting sick., whether other animals are involved in its spread is not known. Plants, arthropods, rodents, and birds have also been considered possible viral reservoirs.Bats were known to roost in the cotton factory in which the first cases of the 1976 and 1979 outbreaks were observed, and they have also been implicated in Marburg virus infections in 1975 and 1980. Of 24 plant and 19 vertebrate species experimentally inoculated with EBOV, only bats became infected. The bats displayed no clinical signs of disease, which is considered evidence that these bats are a reservoir species of EBOV. In a 2002–2003 survey of 1,030 animals including 679 bats from Gabon and the Republic of the Congo, immunoglobulin G immune defense molecules indicative of Ebola infection were found in three bat species; at various periods of study, between 2.2 and 22.6% of bats were found to contain both RNA sequences and IgG molecules indicating Ebola infection. Antibodies against Zaire and Reston viruses have been found in fruit bats in Bangladesh, suggesting that these bats are also potential hosts of the virus and that the filoviruses are present in Asia.
Between 1976 and 1998, in 30,000 mammals, birds, reptiles, amphibians and arthropods sampled from regions of EBOV outbreaks, no Ebola virus was detected apart from some genetic traces found in six rodents and one shrew collected from the Central African Republic. However, further research efforts have not confirmed rodents as a reservoir. Traces of EBOV were detected in the carcasses of gorillas and chimpanzees during outbreaks in 2001 and 2003, which later became the source of human infections. However, the high rates of death in these species resulting from EBOV infection make it unlikely that these species represent a natural reservoir for the virus.