Ebola

Overview

An extremely contagious filovirus causing an acute, usually fatal hemorrhagic fever and spread through contact with bodily fluids of infected persons and by airborne particles.

Symptoms

Symptoms are varied and often appear suddenly. Initial symptoms include high fever (at least 38.8°C; 101.8°F), severe headache, muscle, joint, or abdominal pain, severe weakness and exhaustion, sore throat, nausea, and dizziness.[22] Before an outbreak is suspected, these early symptoms are easily mistaken for malaria, typhoid fever, dysentery, influenza, or various bacterial infections, which are all far more common and reliably less fatal. Ebola may progress to cause more serious symptoms, such as diarrhea, dark or bloody feces, vomiting blood, red eyes due to distension and hemorrhage of sclerotic arterioles, petechia, maculopapular rash, and purpura. Other secondary symptoms include hypotension (low blood pressure), hypovolemia, tachycardia, organ damage (especially the kidneys, spleen, and liver) as a result of disseminated systemic necrosis, and proteinuria. The interior bleeding is caused by a reaction between the virus and the platelets that produces a chemical that will cut cell-sized holes into the capillary walls.

Causes

EVD in humans is caused by four of five viruses of the genus Ebolavirus. The four are Bundibugyo virus (BDBV), Sudan virus (SUDV), Taï Forest virus (TAFV) and one simply called Ebola virus (EBOV, formerly Zaire 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 virus, Reston virus(RESTV), is n

Virology

Main articles: Ebolavirus (taxonomic group) and Ebola virus (specific virus)

Electron micrograph of an Ebola virus virion

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 (BDBV, EBOV, RESTV, SUDV and TAFV) 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, ebolavirions are 80 nanometers (nm) 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 (known as GP1,2) 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 synthesized 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 from. 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

ot thought to cause disease in humans, but has caused disease in other primates. All five viruses are closely related to marburgviruses.

Transmission

Life cycles of the Ebolavirus

Between people, Ebola disease spreads only by direct contact with the blood or body fluids of a person who has developed symptoms of the disease. Body fluids that may contain ebola viruses include saliva, mucus, vomit, feces, sweat, tears, breast milk, urine and semen. The WHO states that only people who are very sick are able to spread Ebola disease in saliva, and whole virus has not been reported to be transmitted through sweat. 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. Ebola may be spread through large droplets; however, this is believed to occur only when a person is very sick. This can happen if a person is splashed with droplets. Contact with surfaces or objects contaminated by the virus, particularly needles and syringes, may also transmit the infection. The virus is able to survive on objects for a few hours in a dried state, and can survive for a few days within body fluids.

The Ebola virus may be able to persist for more than 3 months in the semen after recovery, which could lead to infections via sexual intercourse. Ebola may also occur in the breast milk of women after recovery, and it is not known when it is safe to breastfeed again. The virus was also found in the eye of one patient in 2014, two months after it was cleared from his blood. Otherwise, people who have recovered are not infectious.

The potential for widespread infections in countries with medical systems capable of observing correct medical isolation procedures is considered low. Usually when someone has symptoms of the disease, they are unable to travel without assistance.

Dead bodies remain infectious; thus, people handling human remains in practices such as traditional burial rituals or more modern processes such as embalming are at risk. 69% of the cases of Ebola infections in Guinea during the 2014 outbreak are believed to have been contracted via unprotected (or unsuitably protected) contact with infected corpses during certain Guinean burial rituals.

Health-care workers treating people with Ebola are at greatest risk of infection. The risk increases when they do not have appropriate protective clothing such as masks, gowns, gloves and eye protection; do not wear it properly; or handle contaminated clothing incorrectly. This risk is particularly common in parts of Africa where the disease mostly occurs and health systems function poorly. There has been transmission in hospitals in some African countries that reuse hypodermic needles. Some health-care centers caring for people with the disease do not have running water. In the United States the spread to two medical workers treating infected patients prompted criticism of inadequate training and procedures.

Human-to-human transmission of EBOV through the air has not been reported to occur during EVD outbreaks,[3] and airborne transmission has only been demonstrated in very strict laboratory conditions, and then only from pigs to primates, but not from primates to primates. Spread of EBOV by water, or food other than bushmeat, has not been observed. No spread by mosquitos or other insects has been reported.

The apparent lack of airborne transmission among humans is believed to be due to low levels of the virus in the lungs and other parts of the respiratory system of primates, insufficient to cause new infections. A number of studies examining airborne transmission broadly concluded that transmission from pigs to primates could happen without direct contact because, unlike humans and primates, pigs with EVD get very high ebolavirus concentrations in their lungs, and not their bloodstream. Therefore pigs with EVD can spread the disease through droplets in the air or on the ground when they sneeze or cough. By contrast, humans and other primates accumulate the virus throughout their body and specifically in their blood, but not very much in their lungs. It is believed that this is the reason researchers have observed pig to primate transmission without physical contact, but no evidence has been found of primates being infected without actual contact, even in experiments where infected and uninfed primates shared the same air.

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 sometimes infected with EBOV include several monkey species, chimpanzees, gorillas, baboons 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.

Reservoir

The natural reservoir for Ebola has yet to be confirmed; however, bats are considered to be the most likely candidate species. Three types of fruit bats (Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata) were found to possibly carry the virus without getting sick. As of 2013, whether other animals are involved in its spread is not known. Plants, arthropods 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, 13 fruit bats were found to contain EBOV RNA. 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 (belonging to the species Mus setulosus and Praomys) and one shrew (Sylvisorex ollula) 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.

Prevention

Infection Control

People who care for those infected with Ebola should wear protective clothing including masks, gloves, gowns and goggles. The US Centers for Disease Control (CDC) recommend that the protective gear leaves no skin exposed. These measures are also recommended for those who may handle objects contaminated by an infected person's body fluids. In 2014, the CDC began recommending that medical personnel receive training on the proper suit-up and removal of personal protective equipment (PPE); in addition, a designated person, appropriately trained in biosafety, should be watching each step of these procedures to ensure they are done correctly. In Sierra Leone, the typical training period for the use of such safety equipment lasts approximately 12 days.

The infected person should be in barrier-isolation from other people. All equipment, medical waste, patient waste and surfaces that may have come into contact with body fluids need to be disinfected. During the 2014 outbreak, kits were put together to help families treat Ebola disease in their homes, which include protective clothing as well as chlorine powder and other cleaning supplies. Education of those who provide care in these techniques, and the provision of such barrier-separation supplies has been a priority of Doctors Without Borders.

Ebolaviruses can be eliminated with heat (heating for 30 to 60 minutes at 60 °C or boiling for 5 minutes). To disinfect surfaces, some lipid solvents such as some alcohol-based products, detergents, sodium hypochlorite (bleach) or calcium hypochlorite (bleaching powder), and other suitable disinfectants may be used at appropriate concentrations. Education of the general public about the risk factors for Ebola infection and of the protective measures individuals may take to prevent 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. Some research suggests that an outbreak of Ebola disease in the wild animals used for consumption may result in a corresponding human outbreak. Since 2003, such animal outbreaks have been monitored to predict and prevent Ebola outbreaks in humans.

If a person with Ebola disease dies, direct contact with the body should be avoided. Certain burial rituals, which may have included making various direct contacts with a dead body, require reformulation such that they consistently maintain a proper protective barrier between the dead body and the living. Social anthropologists may help find alternatives to traditional rules for burials.

Transportation crews are instructed to follow a certain isolation procedure should anyone exhibit symptoms resembling EVD. As of August 2014, the WHO does not consider travel bans to be useful in decreasing spread of the disease. In October 2014, the CDC defined four risk levels used to determine the level of 21-day monitoring for symptoms and restrictions on public activities. In the United States, the CDC recommends that restrictions on public activity, including travel restrictions, are not required for the following defined risk levels:

• having been in a country with widespread Ebola disease transmission and having no known exposure (low risk); or having been in that country more than 21 days ago (no risk)
• encounter with a person showing symptoms; but not within 3 feet of the person with Ebola without wearing PPE; and no direct contact of body fluids
• having had brief skin contact with a person showing symptoms of Ebola disease when the person was believed to be not very contagious (low risk)
• in countries without widespread Ebola disease transmission: direct contact with a person showing symptoms of the disease while wearing PPE (low risk)
• contact with a person with Ebola disease before the person was showing symptoms (no risk).

The CDC recommends monitoring for the symptoms of Ebola disease for those both at "low risk" and at higher risk.

In laboratories where diagnostic testing is carried out, biosafety level 4-equivalent containment is required. Laboratory researchers must be properly trained in BSL-4 practices and wear proper PPE

Isolation  

Isolation refers to separating those who are sick from those who are not. Quarantine refers to separating those who may have been exposed to a disease until they either show signs of the disease or are no longer at risk. Quarantine, also known as enforced isolation, is usually effective in decreasing spread. Governments often quarantine areas where the disease is occurring or individuals who may transmit the disease outside of an initial area. In the United States, the law allows quarantine of those infected with ebolaviruses.

Contact Tracing

Contact tracing is considered important to contain an outbreak. It involves finding everyone who had close contact with infected individuals and watching for signs of illness for 21 days. If any of these contacts comes down with the disease, they should be isolated, tested and treated. Then the process is repeated by tracing the contacts' contacts

Diagnosis

When EVD is suspected in a person, his or her travel and work history, along with an exposure to wildlife, are important factors to consider with respect to further diagnostic efforts.

Laboratory Testing

Possible non-specific laboratory indicators of EVD include a low platelet count; an initially decreased white blood cell count followed by an increased white blood cell count; elevated levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and abnormalities in blood clotting often consistent with disseminated intravascular coagulation (DIC) such as a prolonged prothrombin time, partial thromboplastin time, and bleeding time. Filovirions, such as EBOV, may be identified by their unique filamentous shapes in cell cultures examined with electron microscopy, but this method cannot distinguish the various filoviruses.

The specific diagnosis of EVD 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 (PCR) and detecting proteins by enzyme-linked immunosorbent assay (ELISA) are methods best used in the early stages of the disease and also for detecting the virus in human remains. 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 and IgG antibodies can be detected 6 to 18 days after symptom onset. During an outbreak, isolation of the virus via 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. In 2014, with new mobile testing facilities deployed in parts of Liberia, test results were obtained 3–5 hours after sample submission. In 2015 a rapid antigen test which gives results in 15 minutes was approved for use by WHO. It is able to confirm Ebola in 92% of those affected and rule it out in 85% of those not affected.

Differential Diagnosis

Early symptoms of EVD may be similar to those of other diseases common in Africa, including malaria and dengue fever. The symptoms are also similar to those of Marburg virus disease and other viral hemorrhagic fevers.

The complete differential diagnosis is extensive and requires consideration of many other infectious diseases such as typhoid fever, shigellosis, rickettsial diseases, cholera, sepsis, borreliosis, EHEC enteritis, leptospirosis, scrub typhus, plague, Q fever, candidiasis, histoplasmosis, trypanosomiasis, visceral leishmaniasis, measles, and viral hepatitis among others.

Non-infectious diseases that may result in symptoms similar to those of EVD include acute promyelocytic leukemia, hemolytic uremic syndrome, snake envenomation, clotting factor deficiencies/platelet disorders, thrombotic thrombocytopenic purpura, hereditary hemorrhagic telangiectasia, Kawasaki disease, and warfarin poisoning

Prognosis

EVD has a high risk of death in those infected which varies between 25 percent and 90 percent of those infected. As of September 2014, the average risk of death among those infected is 50 percent. The highest risk of death was 90 percent in the 2002–2003 Republic of the Congo outbreak.

Death, if it occurs, follows typically six to sixteen days after symptoms appear and is often due to low blood pressure from fluid loss. Early supportive care to prevent dehydration may reduce the risk of death.

If an infected person survives, recovery may be quick and complete. Prolonged cases are often complicated by the occurrence of long-term problems, such as inflammation of the testicles, joint pains, muscular pain, skin peeling, or hair loss. Eye symptoms, such as light sensitivity, excess tearing, iritis, iridocyclitis, choroiditis, and blindness have also been described

Treatment

There is no standard treatment for Ebola HF. Treatment is primarily supportive and includes minimizing invasive procedures, balancing electrolytes since patients are frequently dehydrated, replacing lost coagulation factors to help stop bleeding, maintaining oxygen and blood levels, and treating any complicating infections. Convalescent plasma (factors from those who have survived Ebola infection) shows promise as a treatment for the disease[citation needed]. Ribavirin is ineffective. Interferon is also thought to be ineffective. In monkeys, administration of an inhibitor of coagulation (rNAPc2) has shown some benefit, protecting 33% of infected animals from a usually 100% (for monkeys) lethal infection (unfortunately, this inoculation does not work on humans). In early 2006, scientists at USAMRIID announced a 75% recovery rate after infecting four rhesus monkeys with Ebolavirus and administering antisense drugs