during evd outbreaks, 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. other possible methods of transmission are being studied. airborne transmission among humans is theoretically possible due to the presence of ebola virus particles in saliva, which can be discharged into the air with a cough or sneeze, but observational data from previous epidemics suggests the actual risk of airborne transmission is low. 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 uninfected primates shared the same air. initial case bushmeat having been smoked in ghana. in africa, wild animals including fruit bats are hunted for food and are referred to as bushmeat. in equatorial africa, human consumption of bushmeat has been linked to animal-to-human transmission of diseases, including ebola. 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 (chimpanzees and gorillas), and duikers (a species of antelope). 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. 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, 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 (igg) 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 (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. deforestation has been mentioned as a possible contributor to recent outbreaks, including the west african ebola virus epidemic. index cases of evd have often been close to recently deforested lands. pathophysiology pathogenesis schematic like other filoviruses, ebov replicates very efficiently in many cells, producing large amounts of virus in monocytes, macrophages, dendritic cells and other cells including liver cells, fibroblasts, and adrenal gland cells. viral replication triggers high levels of inflammatory chemical signals and leads to a septic state. ebov is thought to infect humans through contact with mucous membranes or skin breaks. after infection, endothelial cells (cells lining the inside of blood vessels), liver cells, and several types of immune cells such as macrophages, monocytes, and dendritic cells are the main targets of attack. following infection, immune cells carry the virus to nearby lymph nodes where further reproduction of the virus takes place. from there the virus can enter the bloodstream and lymphatic system and spread throughout the body. macrophages are the first cells infected with the virus, and this infection results 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. this contributes to the weakened immune response seen in those infected with ebov. endothelial cells may be infected within three days after exposure to the virus. the breakdown of endothelial cells leading to blood vessel injury can be attributed to ebov glycoproteins. this damage occurs due to the synthesis of ebola virus glycoprotein (gp), which reduces the availability of specific integrins responsible for cell adhesion to the intercellular structure and causes liver damage, leading to improper clotting. the widespread bleeding that occurs in affected people causes swelling and shock due to loss of blood volume. the dysfunctional bleeding and clotting commonly seen in evd has been attributed to increased activation of the extrinsic pathway of the coagulation cascade due to excessive tissue factor production by macrophages and monocytes. after infection, a secreted glycoprotein, small soluble glycoprotein (sgp or gp) is synthesised. ebov replication overwhelms protein synthesis of infected cells and the host immune defences. the gp forms a trimeric complex, which tethers the virus to the endothelial cells. the sgp forms a dimeric protein that interferes with the signalling of neutrophils, another type of white blood cell. this enables the virus to evade the immune system by inhibiting early steps of neutrophil activation. furthermore, the virus is capable of hijacking cellular metabolism. studies have shown that ebola virus-like particles can reprogram metabolism in both vascular and immune cells. immune system evasion filoviral infection also interferes with proper functioning of the innate immune system. ebov proteins blunt the human immune system's response to viral infections by interfering with the cells' ability to produce and respond to interferon proteins such as interferon-alpha, interferon-beta, and interferon gamma. the vp24 and vp35 structural proteins of ebov play a key role in this interference. when a cell is infected with ebov, receptors located in the cell's cytosol (such as rig-i and mda5) or outside of the cytosol (such as toll-like receptor 3 (tlr3), tlr7, tlr8 and tlr9) recognise infectious molecules associated with the virus. on tlr activation, proteins including interferon regulatory factor 3 and interferon regulatory factor 7 trigger a signalling cascade that leads to the expression of type 1 interferons. the type 1 interferons are then released and bind to the ifnar1 and ifnar2 receptors expressed on the surface of a neighbouring cell. once interferon has bound to its receptors on the neighbouring cell, the signalling proteins stat1 and stat2 are activated and move to the cell's nucleus. this triggers the expression of interferon-stimulated genes, which code for proteins with antiviral properties. ebov's v24 protein blocks the production of these antiviral proteins by preventing the stat1 signalling protein in the neighbouring cell from entering the nucleus. the vp35 protein directly inhibits the production of interferon-beta. by inhibiting these immune responses, ebov may quickly spread throughout the body. diagnosis when evd is suspected, travel, work history, and exposure to wildlife are important factors 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. 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 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. 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 other viral haemorrhagic fevers such as marburg virus disease, crimean–congo haemorrhagic fever, and lassa fever. 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 leukaemia, haemolytic uraemic syndrome, snake envenomation, clotting factor deficiencies/platelet disorders, thrombotic thrombocytopenic purpura, hereditary haemorrhagic telangiectasia, kawasaki disease, and warfarin poisoning. prevention main article: prevention of viral hemorrhagic fever vaccines main article: ebola vaccine 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. it was studied in guinea between 2014 and 2016. more than 100,000 people have been vaccinated against ebola as of 2019. the who reported that approximately 345,000 people were given the vaccine during the kivu ebola epidemic from 2018 to 2020. infection control vhf isolation precautions poster community awareness of the benefits on survival chances of admitting cases early is important for the infected and infection control caregivers british woman wearing protective gear 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 (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