Ebola

• 1. Virology And Pathogenesis

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  Ebolaviruses contain single-stranded, non-infectious RNA genomes. These viral particles measure 80 nanometers in width and can stretch up to 14,000 nanometers in length. They appear as filamentous shapes resembling a shepherd's crook or the number six. The life cycle begins when a virion attaches to specific cell-surface receptors like C-type lectins or DC-SIGN. This attachment allows the viral envelope to fuse with cellular membranes. Inside the cell, the virus travels to acidic endosomes where its glycoprotein GP is cleaved. This processing enables the virus to bind to internal proteins and release its nucleocapsid. The viral RNA polymerase transcribes genes into positive-strand mRNAs which are then translated into structural and nonstructural proteins. Newly synthesized proteins and genomes self-assemble near the inside of the cell membrane before budding off to infect other cells.

  The virus replicates very efficiently in many cells producing large amounts of virus in monocytes, macrophages, dendritic cells, liver cells, fibroblasts, and adrenal gland cells. Viral replication triggers high levels of inflammatory chemical signals leading to a septic state. EBOV is thought to infect humans through contact with mucous membranes or skin breaks. After infection endothelial cells lining blood vessels become main targets of attack. Following infection immune cells carry the virus to nearby lymph nodes where further reproduction takes place. From there the virus can enter the bloodstream and lymphatic system spreading throughout the body. Macrophages are the first cells infected resulting in programmed cell death. Other types of white blood cells such as lymphocytes also undergo programmed cell death leading to an abnormally low concentration of lymphocytes in the blood.

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• 2. Transmission Dynamics And Reservoirs

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  Fruit bats are believed to be the natural host of the viruses without being affected by it. Three types of fruit bats including Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata were found to possibly carry the virus without getting sick. 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 while pigs appear to be able to transmit the virus to at least some primates. Areas undergoing deforestation are among the most likely places for outbreaks due to changes in the landscape bringing wildlife into closer contact with humans. Index cases of Ebola disease have often been close to recently deforested lands.

  It is believed that between people Ebola spreads only by direct contact with the blood or other body fluids of a person who has developed symptoms. Body fluids that may contain Ebola viruses include saliva mucus vomit feces sweat tears breast milk urine and semen. The World Health Organization states that only people who are very sick are able to spread Ebola disease in saliva. Most people spread the virus through blood feces and vomit. Entry points for the virus include the nose mouth eyes open wounds cuts and abrasions. Dead bodies remain infectious thus people handling human remains in practices such as traditional burial rituals are at risk. Of the cases of Ebola infections in Guinea during the 2014 outbreak 69% are believed to have been contracted via unprotected contact with infected corpses.

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• 3. Clinical Presentation And Diagnosis

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  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. Death is often due to shock from fluid loss and typically occurs between six and sixteen days after the first symptoms appear. In about half of the cases the skin may develop a maculopapular rash five to seven days after symptoms begin. Bleeding from mucous membranes or from sites of needle punctures has been reported in 40, 50% of cases.

  The specific diagnosis of Ebola disease is confirmed by isolating the virus detecting its RNA or proteins or detecting antibodies against the virus in a person's blood. Isolating the virus by cell culture detecting the viral RNA by polymerase chain reaction and detecting proteins by enzyme-linked immunosorbent assay are methods best used in the early stages of the disease. Detecting antibodies against the virus is most reliable in the later stages of the disease and in those who recover. IgM antibodies are detectable two days after symptom onset while IgG antibodies can be detected six to 18 days after symptom onset. During an outbreak isolation of the virus with cell culture methods is often not feasible. In field or mobile hospitals the most common and sensitive diagnostic methods are real-time PCR and ELISA.

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• 4. Historical Outbreaks Since 1976

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  The first known outbreak of Ebola occurred between June and November 1976 in Nzara South Sudan caused by Sudan virus. The Sudan outbreak infected 284 people and killed 151. On the 26th of August 1976 the second outbreak began in Yambuku a small rural village in northern Zaire now known as the Democratic Republic of the Congo. This outbreak was caused by EBOV formerly designated Zaire ebolavirus. The first person infected with the disease was the village school's headmaster Mabalo Lokela who began displaying symptoms on the 26th of August 1976. Lokela died on the 8th of September 14 days after he began displaying symptoms.

  In all 318 cases and 280 deaths occurred in Zaire representing an 88% fatality rate. Between 1976 and 2013 the World Health Organization reported 2,387 confirmed cases with 1,590 overall fatalities. The largest outbreak to date was the Ebola virus epidemic in West Africa which caused a large number of deaths in Guinea Sierra Leone and Liberia. In March 2014 the World Health Organization reported a major Ebola outbreak in Guinea tracing it back to a one-year-old child who died in December 2013. By mid-August 2014 Doctors Without Borders reported the situation in Liberia's capital Monrovia was catastrophic and deteriorating daily.

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• 5. Prevention Strategies And Vaccination

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  An Ebola vaccine rVSV-ZEBOV was approved in the United States in December 2019. It appears to be fully effective ten days after being given. More than 100,000 people have been vaccinated against Ebola. The WHO reported that approximately 345,000 people were given the vaccine during the Kivu Ebola epidemic from 2018 to 2020. People who care for those infected with Ebola should wear protective clothing including masks gloves gowns and goggles. The U.S. Centers for Disease Control recommend that the protective gear leaves no skin exposed.

  In 2014 the CDC began recommending that medical personnel receive training on the proper suit-up and removal of personal protective equipment. In Sierra Leone the typical training period for the use of such safety equipment lasts approximately 12 days. Education of the general public about the risk factors for Ebola infection is recommended by the World Health Organization. These measures include avoiding direct contact with infected people and regular hand washing using soap and water. Bushmeat an important source of protein in the diet of some Africans should be handled and prepared with appropriate protective clothing and thoroughly cooked before consumption.

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• 6. Treatment Protocols And Therapeutics

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  Two treatments atoltivimab/maftivimab/odesivimab and ansuvimab are associated with improved outcomes. Early supportive care with rehydration and symptomatic treatment improves survival. Rehydration may be via the oral or intravenous route. These measures may include pain management and treatment for nausea fever and anxiety. The World Health Organization recommends avoiding aspirin or ibuprofen for pain management due to the risk of bleeding associated with these medications. Blood products such as packed red blood cells platelets or fresh frozen plasma may also be used.

  Intensive care is often used in the developed world including maintaining blood volume and electrolytes balance as well as treating any bacterial infections that may develop. Dialysis may be needed for kidney failure while extracorporeal membrane oxygenation may be used for lung dysfunction. In October 2020 the U.S. Food and Drug Administration approved atoltivimab/maftivimab/odesivimab with an indication for the treatment of infection caused by Zaire ebolavirus. By the time the Ebola virus epidemic in West Africa began in 2013 there were at least nine different candidate treatments.

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