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Ebola Wiki
Ebola virus disease
Ebola virus disease (EVD), Ebola hemorrhagic fever (EHF), or simply Ebola is a disease of humans and other primates caused by an ebolavirus. Symptoms start two days to three weeks after contracting the virus, with a fever, sore throat, muscle pain, andheadaches. Typically, vomiting, diarrhea, and rash follow, along with decreased function of the liver and kidneys. Around this time, affected people may begin to bleed both within the body and externally.[1]
The virus may be acquired upon contact with blood or bodily fluids of an infected human or other animal.[1] Spreading through the air has not been documented in the natural environment.[2] Fruit bats are believed to be a carrier and may spread the virus without being affected. Once human infection occurs, the disease may spread between people, as well. Male survivors may be able to transmit the disease via semen for nearly two months. To make the diagnosis, typically other diseases with similar symptoms such as malaria,cholera and other viral hemorrhagic fevers are first excluded. To confirm the diagnosis, blood samples are tested for viral antibodies, viral RNA, or the virus itself.[1]
Prevention includes decreasing the spread of disease from infected animals to humans. This may be done by checking such animals for infection and killing and properly disposing of the bodies if the disease is discovered. Properly cooking meat and wearing protective clothing when handling meat may also be helpful, as are wearing protective clothing and washing hands when around a person with the disease. Samples of bodily fluids and tissues from people with the disease should be handled with special caution.[1]
No specific treatment for the disease is yet available.[1] Efforts to help those who are infected are supportive and include giving eitheroral rehydration therapy (slightly sweet and salty water to drink) or intravenous fluids.[1] This supportive care improves outcomes.[1] The disease has a high risk of death, killing between 50% and 90% of those infected with the virus.[1][3] EVD was first identified in an area ofSudan that is now part of South Sudan, as well as in Zaire (now the Democratic Republic of the Congo). The disease typically occurs in outbreaks in tropical regions of sub-Saharan Africa.[1] From 1976 (when it was first identified) through 2013, the World Health Organization reported a total of 1,716 cases.[1][4] The largest outbreak to date is the ongoing 2014 West African Ebola outbreak, which is affecting Guinea, Sierra Leone, Liberia, and Nigeria.[5][6] As of 28 September 2014, 7,157 suspected cases resulting in the deaths of 3,330 have been reported.[7] Efforts are under way to develop a vaccine; however, none yet exists.[1]
- 1 Signs and symptoms
- 2 Causes
- 3 Pathophysiology
- 4 Diagnosis
- 5 Prevention
- 6 Treatment
- 7 Prognosis
- 8 Epidemiology
- 9 History
- 10 Society and culture
- 11 Other animals
- 12 Research
- 13 See also
- 14 References
- 15 External links
Signs and symptoms
Signs and symptoms of Ebola usually begin suddenly with an influenza-like stage characterized by fatigue, fever, headaches, joint, muscle, and abdominal pain.[9][10] Vomiting, diarrhea, and loss of appetite are also common.[10] Less common symptoms include the following: sore throat, chest pain, hiccups, shortness of breath, and trouble swallowing.[10] The average time between contracting the infection and the start of symptoms (incubation period) is 8 to 10 days, but it can vary between 2 and 21 days.[10][11] Skin manifestations may include amaculopapular rash (in about 50% of cases).[12] Early symptoms of EVD may be similar to those of malaria, dengue fever, or other tropical fevers, before the disease progresses to the bleeding phase.[9]
In 40–50% of cases, bleeding from puncture sites and mucous membranes (e.g., gastrointestinal tract, nose, vagina, and gums) has been reported.[13] In the bleeding phase, which typically begins five to seven days after first symptoms,[14] internal and subcutaneous bleeding may present itself in the form of reddened eyes and bloody vomit.[9] Bleeding into the skin may create petechiae, purpura, ecchymoses, andhematomas (especially around needle injection sites). Sufferers may cough up blood, vomit it, or excrete it in their stool.
Heavy bleeding is rare and is usually confined to the gastrointestinal tract.[12][15] In general, the development of bleeding symptoms often indicates a worse prognosis and this blood loss can result in death.[9] All people infected show some signs of circulatory system involvement, including impaired blood clotting.[12] If the infected person does not recover, death due to multiple organ dysfunction syndrome occurs within 7 to 16 days (usually between days 8 and 9) after first symptoms.[14]
EVD is caused by four of five viruses classified in the genus Ebolavirus, family Filoviridae, order Mononegavirales. The four disease-causing viruses are Bundibugyo virus (BDBV), Sudan virus (SUDV), Taï Forest virus (TAFV), and one called, simply, Ebola virus (EBOV, formerly Zaire Ebola virus)). Ebola virus is the sole member of the Zaire ebolavirus species and the most dangerous of the known Ebola disease-causing viruses, as well as being responsible for the largest number of outbreaks.[16] The fifth virus, Reston virus (RESTV), is not thought to be disease-causing in humans. These five viruses are closely related to the Marburg viruses.
Human-to-human transmission can occur via direct contact with blood or bodily fluids from an infected person (including embalming of an infected dead person) or by contact with objects contaminated by the virus, particularly needles and syringes.[17] Other body fluids with ebola virus include saliva, mucus, vomit, feces, sweat, tears, breast milk, urine, and semen. Entry points include the nose, mouth, eyes, or open wounds, cuts and abrasions. [18] The potential for widespread EVD infections is considered low as the disease is only spread by direct contact with the secretions from someone who is showing signs of infection.[17] The symptoms limit a person's ability to spread the disease as they are often too sick to travel.[19] Because dead bodies are still infectious, traditional burial rituals may spread the disease. Nearly two thirds of the cases of Ebola in Guinea during the 2014 outbreak are believed to be due to burial practices.[20][21] Semen may be infectious in survivors for up to 3 months.[22] It is not entirely clear how an outbreak is initially started.[23] The initial infection is believed to occur after ebola virus is transmitted to a human by contact with an infected animal's body fluids.
One of the primary reasons for spread is that the health systems in the part of Africa where the disease occurs function poorly.[24] Medical workers who do not wear appropriate protective clothing may contract the disease.[25] Hospital-acquired transmission has occurred in African countries due to the reuse of needles and lack of universal precautions.[26][27]Some healthcare centers caring for people with the disease do not have running water.[22]
Airborne transmission has not been documented during EVD outbreaks.[2] They are, however, infectious as breathable 0.8– to 1.2-μm laboratory-generated droplets.[28] The virus has been shown to travel, without contact, from pigs to primates, although the same study failed to demonstrate similar transmission between non-human primates.[29]
Bats drop partially eaten fruits and pulp, then land mammals such as gorillas and duikers feed on these fallen fruits. This chain of events forms a possible indirect means of transmission from the natural host to animal populations, which has led to research towards viral shedding in the saliva of bats. Fruit production, animal behavior, and other factors vary at different times and places that may trigger outbreaks among animal populations.[30]
Bats are considered the most likely natural reservoir of the EBOV. Plants, arthropods, and birds were also considered.[1][32] Bats were known to reside in the cotton factory in which the first cases for the 1976 and 1979 outbreaks were observed, and they have also been implicated in Marburg virus infections in 1975 and 1980.[33] Of 24 plant species and 19 vertebrate species experimentally inoculated with EBOV, only bats became infected.[34] The absence of clinical signs in these bats is characteristic of a reservoir species. 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 fragments.[35]As of 2005, three types of fruit bats (Hypsignathus monstrosus, Epomops franqueti, and Myonycteris torquata) have been identified as being in contact with EBOV. They are now suspected to represent the EBOV reservoir hosts.[36][37] Antibodies against Zaire and Reston viruses have been found in fruit bats in Bangladesh, thus identifying potential virus hosts and signs of the filoviruses in Asia.[38]
Between 1976 and 1998, in 30,000 mammals, birds, reptiles, amphibians and arthropods sampled from outbreak regions, no ebolavirus was detected apart from some genetic traces found in six rodents (Mus setulosus and Praomys) and one shrew (Sylvisorex ollula) collected from the Central African Republic.[33][39] 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 lethality from infection in these species makes them unlikely as a natural reservoir.[33]
Transmission between natural reservoir and humans is rare, and outbreaks are usually traceable to a single case where an individual has handled the carcass of gorilla, chimpanzee or duiker.[40] Fruit bats are also eaten by people in parts of West Africa where they are smoked, grilled or made into a spicy soup.[37][41]
Like all mononegaviruses, ebolavirions contain linear nonsegmented, single-strand, non-infectious RNA genomes of negative polarity that possesses inverse-complementary 3′ and 5′ termini, do not possess a 5′ cap, are not polyadenylated, and are not covalently linked to aprotein.[42] Ebolavirus genomes are approximately 19 kilobase pairs long and contain seven genes in the order 3′-UTR–NP–VP35–VP40–GP–VP30–VP24–L–5′-UTR.[43] The genomes of the five different ebolaviruses (BDBV, EBOV, RESTV, SUDV, and TAFV) differ in sequence and the number and location of gene overlaps.
Like all filoviruses, ebolavirions are filamentous particles that may appear in the shape of a shepherd's crook or in the shape of a "U" or a "6", and they may be coiled, toroid, or branched.[43] In general, ebolavirions are 80 nm in width, but vary somewhat in length. In general, the median particle length of ebolaviruses ranges from 974 to 1,086 nm (in contrast to marburgvirions, whose median particle length was measured at 795–828 nm), but particles as long as 14,000 nm have been detected in tissue culture.[44]
The ebolavirus life cycle begins with virion attachment to specific cell-surface receptors, followed by fusion of the virion envelope with cellular membranes and the concomitant release of the virus nucleocapsid into the cytosol. 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. Ebolavirus RNA polymerase (L) binds to a single promoter located at the 3′ end of the genome. Transcription either terminates after a gene or continues to the next gene downstream. This means that genes close to the 3′ end of the genome are transcribed in the greatest abundance, whereas those toward the 5′ end are least likely to be transcribed. The gene order is, therefore, a simple but effective form of transcriptional regulation. The most abundant protein produced is the nucleoprotein, whose concentration in the cell determines when L switches from gene transcription to genome replication. Replication results in full-length, positive-strand antigenomes that are, in turn, transcribed into negative-strand virus progeny genome copy. 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 they bud from. The mature progeny particles then infect other cells to repeat the cycle. The Ebola virus genetics are difficult to study due to its virulent nature.[45]
Endothelial cells, macrophages, monocytes, and liver cells are the main targets of infection. After infection, a secreted glycoprotein (sGP) known as the Ebola virus glycoprotein (GP) is synthesized. Ebola replication overwhelms protein synthesis of infected cells and host immune defenses. The GP forms a trimeric complex, which binds the virus to the endothelial cells lining the interior surface of blood vessels. The sGP forms a dimeric protein that interferes with the signaling of neutrophils, a type of white blood cell, which allows the virus to evade the immune system by inhibiting early steps of neutrophil activation. These white blood cells also serve as carriers to transport the virus throughout the entire body to places such as the lymph nodes, liver, lungs, and spleen.[46]
The presence of viral particles and cell damage resulting from budding causes the release of chemical signals (to be specific, TNF-α, IL-6, IL-8, etc.), which are the signaling molecules for fever and inflammation. The cytopathic effect, from infection in the endothelial cells, results in a loss of vascular integrity. This loss in vascular integrity is furthered with synthesis of GP, which reduces specific integrins responsible for cell adhesion to the inter-cellular structure, and damage to the liver, which leads to improper clotting.[47]
The travel and work history along with exposure to wildlife are important to consider when the diagnosis of EVD is suspected. The diagnosis 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) works best early and in those who have died from the disease. Detecting antibodies against the virus works best late in the disease and in those who recover.[48]
During an outbreak, virus isolation is often not feasible. The most common diagnostic methods are therefore real-time PCR and ELISA detection of proteins, which can be performed in field or mobile hospitals.[49] Filovirions can be seen and identified in cell culture by electron microscopy due to their unique filamentous shapes, but electron microscopy cannot tell the difference between the various filoviruses despite there being some length differences.[44]
The genera Ebolavirus and Marburgvirus were originally classified as the species of the now-obsolete Filovirus genus. In March 1998, the Vertebrate Virus Subcommittee proposed in the International Committee on Taxonomy of Viruses (ICTV) to change the Filovirus genus to the Filoviridae family with two specific genera: Ebola-like viruses and Marburg-like viruses. This proposal was implemented in Washington, DC, on April 2001 and in Paris on July 2002. In 2000, another proposal was made in Washington, D.C., to change the "-like viruses" to "-virus" resulting in today's Ebolavirus and Marburgvirus.[50]
Rates of genetic change are 100 times slower than influenza A in humans, but on the same magnitude as those of hepatitis B.Extrapolating backwards using these rates indicates that Ebolavirus and Marburgvirus diverged several thousand years ago.[51]However, paleoviruses (genomic fossils) of filoviruses (Filoviridae) found in mammals indicate that the family itself is at least tens of millions of years old.[52] Fossilized viruses that are closely related to ebolaviruses have been found in the genome of theChinese hamster.[53]
Differential diagnosis
The symptoms of EVD are similar to those of Marburg virus disease.[54] It can also easily be confused with many other diseases common in Equatorial Africa such as other viral hemorrhagic fevers, falciparum malaria, typhoid fever, shigellosis, rickettsial diseases such as typhus, cholera, gram-negative septicemia, borreliosis such as relapsing fever orEHEC enteritis. Other infectious diseases that should be included in the differential diagnosis include the following: leptospirosis, scrub typhus, plague, Q fever, candidiasis,histoplasmosis, trypanosomiasis, visceral leishmaniasis, hemorrhagic smallpox, measles, and fulminant viral hepatitis.[55] Non-infectious diseases that can be confused with EVD areacute promyelocytic leukemia, hemolytic uremic syndrome, snake envenomation, clotting factor deficiencies/platelet disorders, thrombotic thrombocytopenic purpura, hereditary hemorrhagic telangiectasia, Kawasaki disease, and even warfarin poisoning.[56][57][58][59]
Infection control and containment
The risk of transmission is increased among those caring for people infected. Recommended measures when caring for those who are infected include isolating them, sterilizing equipment and surfaces, and wearing protective clothing including masks, gloves, gowns, and goggles.[23] If a person with Ebola dies, direct contact with the body of the deceased patient should be avoided.[23]
In order to reduce the spread, the World Health Organization recommends raising community awareness of the risk factors for Ebola infection and the protective measures individuals can take.[60] These include avoiding contact with infected people and regular hand washingusing soap and water.[61] Traditional burial rituals, especially those requiring washing or embalming of bodies, should be discouraged or modified.[62][63] Social anthropologists may help find alternatives to traditional rules for burials.[64] Airline crews are instructed to isolate anyone who has symptoms resembling Ebola virus.[65]
The Ebola virus can be eliminated with heat (heating for 30 to 60 minutes at 60 °C or boiling for 5 minutes). On surfaces, some lipid solvents such as some alcohol-based products, detergents, sodium hypochlorite (bleach) or calcium hypochlorite (bleaching powder), and other suitable disinfectants at appropriate concentrations can be used as disinfectants.[66][67]
In laboratories where diagnostic testing is carried out, biosafety level 4-equivalent containment is required, since Ebola viruses are World Health Organization Risk Group 4 pathogens. Laboratory researchers must be properly trained in BSL-4 practices and wear proper personal protective equipment.
Quarantine, also known as enforced isolation, is usually effective in decreasing spread.[68][69] Governments often quarantine areas where the disease is occurring or individuals who may be infected.[70] In the United States, the law allows quarantine of those infected with Ebola.[71] During the 2014 outbreak, Liberia closed schools.[72]
Contact tracing
Contact tracing is regarded as 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 repeat the process by tracing the contacts' contacts.[73][74]
Standard support
No ebolavirus-specific treatment is currently approved.[75] However, survival is improved by early supportive care with rehydration and symptomatic treatment.[1] Treatment is primarily supportive in nature.[76] These measures may include management of pain, nausea, feverand anxiety, as well as rehydration via the oral or by intravenous route.[76] Blood products such as packed red blood cells, platelets or fresh frozen plasma may also be used.[76] Other regulators of coagulation have also been tried including heparin in an effort to preventdisseminated intravascular coagulation and clotting factors to decrease bleeding.[76] Antimalarial medications and antibiotics are often used before the diagnosis is confirmed,[76] though there is no evidence to suggest such treatment is in any way helpful.
Intensive care
Intensive care is often used in the developed world.[77] This may include maintaining blood volume and electrolytes (salts) balance as well as treating any bacterial infections that may develop.[77] Dialysis may be needed for kidney failure while extracorporeal membrane oxygenationmay be used for lung dysfunction.[77]
The disease has a high mortality rate: often between 25 percent and 90 percent.[1][3] As of September 2014, information from WHO across all occurrences to date puts the overall fatality rate at 50%.[1] There are indications based on variations in death rate between countries that early and effective treatment of symptoms (e.g., supportive care to prevent dehydration) may reduce the fatality rate significantly.[78] 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, muscle pains, skin peeling, or hair loss. Eye symptoms, such as light sensitivity, excess tearing,iritis, iridocyclitis, choroiditis, and blindness have also been described. EBOV and SUDV may be able to persist in the semen of some survivors for up to seven weeks, which could give rise to infections and disease via sexual intercourse.[1]
The disease typically occurs in outbreaks in tropical regions of Sub-Saharan Africa.[1] From 1976 (when it was first identified) through 2013, the World Health Organization reported 1,716 confirmed cases.[1][4] The largest outbreak to date is the ongoing 2014 West Africa Ebola virus outbreak, which is affecting Guinea, Sierra Leone, Liberia and Nigeria.[5][6] As of 13 August, 2,127 cases have been identified, with 1,145 deaths.[5]
The first identified case of Ebola was on 26 August 1976, in Yambuku, a small rural village in Mongala District in northern Democratic Republic of the Congo (then known as Zaire).[79] The first victim, and the index case for the disease, was village school headmaster Mabalo Lokela, who had toured an area near the Central African Republic border along the Ebola river between 12–22 August. On 8 September he died of what would become known as the Ebola virus species of the ebolavirus.[80] Subsequently a number of other cases were reported, almost all centered on the Yambuku mission hospital or having close contact with another case.[80] 318 cases and 280 deaths (a 88% fatality rate) occurred in the DRC.[81] The Ebola outbreak was contained with the help of the World Health Organization and transport from the Congolese air force, by quarantining villagers, sterilizing medical equipment, and providing protective clothing. The virus responsible for the initial outbreak, first thought to be Marburg virus, was later identified as a new type of virus related to Marburg, and named after the nearby Ebola river. Another ebolavirus, the Sudan virus species, was also identified that same year when an outbreak occurred in Sudan, affecting 284 people and killing 151.[82]
1995 to 2013
The second major outbreak occurred in 1995 in the Democratic Republic of Congo, affecting 315 and killing 254. The next major outbreak occurred in Uganda in 2000, affecting 425 and killing 224; in this case the Sudan virus was found to be the ebolavirus species responsible for the outbreak.[83] In 2003 there was an outbreak in the Republic of Congo that affected 143 and killed 128, a death rate of 90%, the highest to date.[84]
In August 2007, 103 people were infected by a suspected hemorrhagic fever outbreak in the village of Kampungu, Democratic Republic of the Congo. The outbreak started after the funerals of two village chiefs, and 217 people in four villages fell ill.[83][85][86] The 2007 outbreak eventually affected 264 individuals and resulted in the deaths of 187.[1]
On 30 November 2007, the Uganda Ministry of Health confirmed an outbreak of Ebola in the Bundibugyo District in Western Uganda. After confirmation of samples tested by the United States National Reference Laboratories and the Centers for Disease Control, the World Health Organization confirmed the presence of a new species of Ebolavirus, which was tentatively named Bundibugyo.[87] The WHO reported 149 cases of this new strain and 37 of those led to deaths.[1]
The WHO confirmed two small outbreaks in Uganda in 2012. The first outbreak affected 7 people and resulted in the death of 4 and the second affected 24, resulting in the death of 17. The Sudan variant was responsible for both outbreaks.[1]
On 17 August 2012, the Ministry of Health of the Democratic Republic of the Congo reported an outbreak of the Ebola-Bundibugyo variant[88] in the eastern region.[89][90] Other than its discovery in 2007, this was the only time that this variant has been identified as the ebolavirus responsible for an outbreak. The WHO revealed that the virus had sickened 57 people and claimed 29 lives. The probable cause of the outbreak was tainted bush meat hunted by local villagers around the towns of Isiro and Viadana.[1][91]
2014 outbreak
In March 2014, the World Health Organization (WHO) reported a major Ebola outbreak in Guinea, a western African nation.[92]Researchers traced the outbreak to a two-year old child who died on 28 December 2013.[93][94] The disease then rapidly spread to the neighboring countries of Liberia and Sierra Leone. It is the largest Ebola outbreak ever documented, and the first recorded in the region.[92]
On 8 August 2014, the WHO declared the epidemic to be an international public health emergency. Urging the world to offer aid to the affected regions, the Director-General said, "Countries affected to date simply do not have the capacity to manage an outbreak of this size and complexity on their own. I urge the international community to provide this support on the most urgent basis possible."[95] By mid-August 2014, Doctors Without Borders reported the situation in Liberia's capital Monrovia as "catastrophic" and "deteriorating daily". They reported that fears of Ebola among staff members and patients had shut down much of the city's health system, leaving many people without treatment for other conditions.[96] By late August 2014, the disease had spread to Nigeria, and one case was reported in Senegal.[97][98] [99][100] On 30 September 2014, the first confirmed case of Ebola was diagnosed in the United States at Texas Health Presbyterian Hospital in Dallas, Texas.[101]
Aside from the human cost, the outbreak has severely eroded the economies of the affected countries. A Financial Times report suggested the economic impact of the outbreak could kill more people than the virus itself. As of 23 September, in the three hardest hit countries, Liberia, Sierra Leone, and Guinea, there were only 893 treatment beds available while the current need was 2122. In a 26 September statement, the WHO said, "The Ebola epidemic ravaging parts of West Africa is the most severe acute public health emergency seen in modern times. Never before in recorded history has a biosafety level four pathogen infected so many people so quickly, over such a broad geographical area, for so long."[102]
By 29 September 2014, 7,192 suspected cases and 3,286 deaths had been reported, however the World Health Organization has said that these numbers may be vastly underestimated.[103] The WHO reports that more than 216 healthcare workers are among the dead, partly due to the lack of equipment and long hours.[104][105]
The first recorded outbreak of EBD occurred in Southern Sudan in June 1976. A second outbreak soon followed in theDemocratic Republic of the Congo (then Zaire).[106] Virus isolated from both outbreaks was named "Ebola virus" by Belgian researchers[107] after the Ebola River, located near the Zaire outbreak.[108] Although it was assumed that the two outbreaks were connected, scientists later realized that they were caused by distinct species of filoviruses, Sudan virus and Ebola virus.[106]
In late 1989, Hazelton Research Products' Reston Quarantine Unit in Reston, Virginia suffered a mysterious outbreak of fatal illness (initially diagnosed as Simian hemorrhagic fever virus (SHFV)) among a shipment of crab-eating macaquemonkeys imported from the Philippines. Hazelton's veterinary pathologist sent tissue samples from dead animals to theUnited States Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick, Maryland, where a laboratory test known as an ELISA assay showed antibodies to Ebola virus.[109] An electron microscopist from USAMRIID discovered filoviruses similar in appearance to Ebola in the tissue samples sent from Hazelton Research Products' Reston Quarantine Unit.[110]
Shortly afterward, a US Army team headquartered at USAMRIID went into action to euthanize the monkeys which had not yet died, bringing those monkeys and those which had already died of the disease to Ft. Detrick for study by the Army's veterinary pathologists and virologists, and eventual disposal under safe conditions.[109]
Blood samples were taken from 178 animal handlers during the incident.[111] Of those, six animal handlers eventually seroconverted, including one who had cut himself with a bloody scalpel.[112][46] When the handlers did not become ill, the CDC concluded that the virus had a very low pathogenicity to humans.[112]
The Philippines and the United States had no previous cases of Ebola infection, and upon further isolation, researchers concluded it was another strain of Ebola, or a new filovirus of Asian origin, which they named Reston ebolavirus (REBOV) after the location of the incident.[109]
Society and culture
Ebolavirus is classified as a biosafety level 4 agent, as well as a Category A bioterrorism agent by the Centers for Disease Control and Prevention. It has the potential to be weaponized for use in biological warfare,[113][114] and was investigated by the Biopreparat for such use, but might be difficult to prepare as a weapon of mass destruction because the virus becomes ineffective quickly in open air.[115]
Richard Preston's 1995 best-selling book, The Hot Zone, dramatized the Ebola outbreak in Reston, Virginia.[116]
William Close's 1995 Ebola: A Documentary Novel of Its First Explosion and 2002 Ebola: Through the Eyes of the People focused on individuals' reactions to the 1976 Ebola outbreak in Zaire.[117]
Tom Clancy's 1996 novel, Executive Orders, involves a Middle Eastern terrorist attack on the United States using an airborne form of a deadly Ebola virus strain named "Ebola Mayinga" (see Mayinga N'Seka).[118]
Other animals
Wild animals
It is widely believed that outbreaks of EVD among human populations result from handling infected wild animal carcasses. Some research suggests that an outbreak in the wild animals used for consumption, bushmeat, may result in a corresponding human outbreak. Since 2003, such outbreaks have been monitored through surveillance of animal populations with the aim of predicting and preventing Ebola outbreaks in humans.[119]
Recovered carcasses from gorillas contain multiple Ebola virus strains, which suggest multiple introductions of the virus. Bodies decompose quickly and carcasses are not infectious after three to four days. Contact between gorilla groups is rare, suggesting transmission among gorilla groups is unlikely, and that outbreaks result from transmission between viral reservoir and animal populations.[120]
Ebola has a high mortality among primates.[121] Frequent outbreaks of Ebola may have resulted in the deaths of 5,000 gorillas.[122] Outbreaks of Ebola may have been responsible for an 88% decline in tracking indices of observed chimpanzee populations in 420 square kilometer Lossi Sanctuary between 2002 and 2003.[120] Transmission among chimpanzees through meat consumption constitutes a significant risk factor, while contact between individuals, such as touching dead bodies and grooming, is not.[123]
Domesticated animals
Reston ebolavirus (REBOV) can be transmitted to pigs.[124] This virus was discovered during an outbreak of what at the time was thought to be simian hemorrhagic fever virus(SHFV) in crab-eating macaques in Reston, Virginia (hence the name Reston elabavirus) in 1989. Since the initial outbreak it has since been found in nonhuman primates in Pennsylvania, Texas, and Italy. In each case, the affected animals had been imported from a facility in the Philippines,[70] where the virus had infected pigs.[125] Despite its status as a Level‑4 organism and its apparent pathogenicity in monkeys, REBOV has not caused disease in exposed human laboratory workers.[126] In 2012 it was demonstrated that the virus can travel without contact from pigs to nonhuman primates, although the same study failed to achieve transmission in that manner between primates.[124] According to the WHO, routine cleaning and disinfection of pig (or monkey) farms with sodium hypochlorite or other detergents should be effective in inactivating the Reston ebolavirus. If an outbreak is suspected, the area must be immediately quarantined.[82]
While pigs that have been infected with REBOV tend to show symptoms of the disease, it has been shown that dogs may become infected with EBOV and remain asymptomatic. Dogs in some parts of Africa scavenge for their food and it is known that they sometimes eat infected animals and the corpses of humans. Although they remain asymptomatic, a 2005 survey of dogs during an EBOV outbreak found that over 31.8% showed a seroprevalence for EBOV closest to an outbreak versus 9% a farther distance away.[127]
A number of experimental treatments are being studied.[128] In the United States, the Food and Drug Administration (FDA)'s animal efficacy rule is being used to demonstrate reasonable safety to obtain permission to treat people who are infected with Ebola. It is being used as the normal path for testing drugs is not possible for diseases caused by dangerous pathogens or toxins. Experimental drugs are made available for use with the approval of regulatory agencies under named patient programs, known in the US as"expanded access".[129]
As of August 14, 2014, the United States Food and Drug Administration (FDA) has not approved any drugs to treat or prevent Ebola and advises people to watch out for fraudulent products.[130] The unavailability of experimental treatments in the most affected regions during the 2014 outbreak spurred controversy, with some calling for experimental drugs to be made more widely available in Africa on a humanitarian basis, and others warning that making unproven experimental drugs widely available would be unethical, especially in light of past experimentation conducted in developing countries by Western drug companies.[131][132]
On 12 August the WHO released a statement that the use of not yet proven treatments is ethical in certain situations in an effort to treat or prevent the disease.[133] The FDA has allowed three drugs: ZMapp, an RNA interference drug called TKM-Ebola, and brincidofovir to be used in people infected with Ebola under these programs during the 2014 outbreak.[134][135] BioCryst's BCX4430 small molecule is undergoing further animal testing as a possible therapy in humans.[136] Another drug favipiravir has been used with apparent success in a patient medically evacuated to France.[137]
Officially endorsed experimental treatments
- The WHO has recognised that transfusion of whole blood or purified serum from Ebola survivors is the therapy with the greatest potential to be implemented immediately, although there is little information as to its efficacy.[138] At the end of September, WHO issued an interim guideline for this therapy.[139] The blood serum from those who have survived an infection is currently being studied to see if it is an effective treatment.[140] During a meeting arranged by WHO this research was deemed to be a top priority.[140] Seven of eight people with Ebola survived after receiving a transfusion of blood donated by individuals who had previously survived the infection in an 1999 outbreak in the Democratic Republic of the Congo.[76][141] This treatment, however, was started late in the disease meaning they may have already been recovering on their own and the rest of their care was better than usual.[76] Thus this potential treatment remains controversial.[77] Intravenous antibodies appear to be protective in non-human primates who have been exposed to large doses of Ebola.[142] The World Health Organisation has approved the use of convalescent serum and whole blood products to treat people with Ebola.[143]
- ZMapp is a monoclonal antibody vaccine. The limited supply of the drug has been used to treat a small number of individuals infected with the Ebola virus. Although some of these have recovered the outcome is not considered statistically significant.[144] ZMapp has proved effective in a trial involving Rhesus macaque monkeys.[145]
- Favipiravir, an anti-viral drug approved in Japan for stockpiling against influenza pandemics, appears to be useful in a mouse model of Ebola.[9][146] On 4 October 2014, it was reported that a French nun who contracted Ebola while volunteering in Liberia was cured with Favipiravir treatment.[147]
- BCX4430 is a broad-spectrum antiviral drug developed by BioCryst Pharmaceuticals and currently being researched as a potential treatment for Ebola by USAMRIID.[148] The drug has been approved to progress to Phase 1 trials, expected late in 2014.[149]
- Brincidofovir, another broad-spectrum antiviral drug, has been granted an emergency FDA approval as an investigational new drug for the treatment of Ebola, after it was found to be effective against Ebolavirus in in vitro tests.[150] It has subsequently been used to treat the first patient diagnosed with Ebola in the USA, after he had recently returned from Liberia.[151]
- Other promising treatments rely on antisense technology. Both small interfering RNAs (siRNAs) and phosphorodiamidate morpholino oligomers (PMOs) targeting the Zaire Ebola virus (ZEBOV) RNA polymerase L protein could prevent disease in nonhuman primates.[152][153] TKM-Ebola is a small-interfering RNA compound, currently being tested in a Phase I clinical trial in humans.[134][154] Sarepta Therapeutics has completed a phase I clinical trial with its Morpholino oligo targeting Ebola.[155]
Speculative and unproven treatments
- Two selective estrogen receptor modulators used to treat infertility and breast cancer (clomiphene and toremifene) have been found to inhibit the progress of Ebola virus in infected mice.[156] Ninety percent of the mice treated with clomiphene and fifty percent of those treated with toremifene survived the tests.[156]
- A 2014 study found that three ion channel blockers used in the treatment of heart arrhythmias, amiodarone, dronedarone and verapamil, block the entry of ebola virus into cells in vitro.[157] Given their oral availability and history of human use, these drugs would be candidates for treating Ebola virus infection in remote geographical locations, either on their own or together with other antiviral drugs
As of September 2014, no vaccine was approved for clinical use in humans.[140][130] It was hoped that one would be initially available by November 2014.[140] The most promising candidates are DNA vaccines[158] or vaccines derived from adenoviruses,[159] vesicular stomatitis Indiana virus (VSIV)[160][161][162] or filovirus-like particles (VLPs)[163] because these candidates could protect nonhuman primates from ebolavirus-induced disease. DNA vaccines, adenovirus-based vaccines, and VSIV-based vaccines have entered clinical trials.[164][165][166][167]
Vaccines have protected nonhuman primates. Immunization takes six months, which impedes the counter-epidemic use of the vaccines. Searching for a quicker onset of effectiveness, in 2003, a vaccine using an adenoviral (ADV) vector carrying the Ebola spike protein was tested on crab-eating macaques. Twenty-eight days later, they were challenged with the virus and remained resistant.[159] A vaccine based on attenuated recombinant vesicular stomatitis virus (VSV) vector carrying either the Ebola glycoprotein or the Marburg glycoprotein in 2005 protected nonhuman primates,[168] opening clinical trials in humans.[164] The study by October completed the first human trial, over three months giving three vaccinations safely inducing an immune response. Individuals for a year were followed, and, in 2006, a study testing a faster-acting, single-shot vaccine began; this new study was completed in 2008.[165] Trying the vaccine on a strain of Ebola that more resembles one that infects humans is the next step.[169] On 6 December 2011, the development of a successful vaccine against Ebola for mice was reported. Unlike the predecessors, it can be freeze-dried and thus stored for long periods in wait for an outbreak.[170] An experimental vaccine made by researchers at Canada's national laboratory in Winnipeg was used, in 2009, to pre-emptively treat a German scientist who might have been infected during a lab accident.[171] However, actual EBOV infection was never demonstrated beyond doubt.[172] Experimentally, recombinant vesicular stomatitis Indiana virus (VSIV) expressing the glycoprotein of EBOV or SUDV has been used successfully in nonhuman primate models as post-exposure prophylaxis.[173][174] The CDC's recommendations are currently under review.[citation needed]
Simultaneous phase 1 trials of an experimental vaccine known as the NIAID/GSK vaccine commenced in September 2014.[175] GlaxoSmithKline and the NIH jointly developed the vaccine,[175] based on a modified chimpanzee adenovirus, and contains parts of the Zaire and Sudan ebola strains.[175] If this phase is completed successfully, the vaccine will be fast tracked for use in West Africa. In preparation for this, GSK is preparing a stockpile of 10,000 doses.[176][177]
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(3) Stone, Oliver (1996-09-02). "Who's That in the Oval Office?". Books News & Reviews. The New York Times Company. Archived from the original on 2009-04-10. Retrieved 2014-09-10.
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- ^ Jump up to:a b Leroy EM, Rouquet P, Formenty P, Souquière S, Kilbourne A, Froment JM, Bermejo M, Smit S, Karesh W, Swanepoel R, Zaki SR, Rollin PE (2004). "Multiple Ebola virus transmission events and rapid decline of central African wildlife". Science 303 (5656): 387–390. Bibcode:2004Sci…303..387L. doi:10.1126/science.1092528. PMID 14726594.
- Jump up^ Choi JH, Croyle MA (2013). "Emerging targets and novel approaches to Ebola virus prophylaxis and treatment". BioDrugs 27 (6): 565–83. doi:10.1007/s40259-013-0046-1.PMID 23813435.
- Jump up^ Ebola 'kills over 5,000 gorillas'. BBC. 2006-12-08. Retrieved 2009-05-31.
- Jump up^ Formenty P, Boesch C, Wyers M, Steiner C, Donati F, Dind F, Walker F, Le Guenno B (1999). "Ebola virus outbreak among wild chimpanzees living in a rain forest of Côte d'Ivoire". The Journal of infectious diseases. 179. Suppl 1 (s1): S120–S126.doi:10.1086/514296. PMID 9988175.
- ^ Jump up to:a b Weingartl HM, Nfon C, Kobinger G (2013). "Review of Ebola virus infections in domestic animals". Dev Biol (Basel) 135: 211–8. doi:10.1159/000178495.PMID 23689899.
- Jump up^ McNeil Jr, Donald G. (2009-01-24). "Pig-to-Human Ebola Case Suspected in Philippines". New York Times. Retrieved 2009-01-26.
- Jump up^ McCormick & Fisher-Hoch 1999, p. 300
- Jump up^ Allela L, Boury O, Pouillot R, Délicat A, Yaba P, Kumulungui B, Rouquet P, Gonzalez JP, Leroy EM (2005). "Ebola virus antibody prevalence in dogs and human risk". Emerging Infect. Dis. 11 (3): 385–90. doi:10.3201/eid1103.040981. PMC 3298261.PMID 15757552.
- Jump up^ Briggs H. "BBC News – Ebola: Experimental drugs and vaccines". BBC News. Retrieved 2014-08-08.
- Jump up^ Gaffney A (2014-08-07). "Regulatory Explainer: What You Need to Know About the Regulation of Ebola Treatments". Regulatory Affairs Professionals Society (RAPS).
- ^ Jump up to:a b "FDA warns consumers about fraudulent Ebola treatment products". Retrieved 20 August 2014.
- Jump up^ "Three leading Ebola experts call for release of experimental drug". Los Angeles Times. 2014-08-06.
- Jump up^ "In Ebola Outbreak, Who Should Get Experimental Drug?". The New York Times. 2014-08-08.
- Jump up^ "Ethical considerations for use of unregistered interventions for Ebola virus disease (EVD)". WHO. Retrieved 20 August 2014.
- ^ Jump up to:a b Pollack, Andrew (07 August 2014). "Second drug is allowed for treatment of Ebola". The New York Times. Retrieved 8 August 2014.
- Jump up^ Perrone, Matthew (10/6/14). "Experimental Drug Provided to Dallas Ebola Patient". ABC. AP. Retrieved 10/6/14.
- Jump up^ Forbes – BioCryst to Launch NHP Ebola Drug Safety, Efficacy Studies 'Within Weeks'
- Jump up^ http://www.msn.com/en-gb/news/world/french-nurse-cured-of-ebola-contracted-in-liberia/ar-BB7r1UJ
- Jump up^ "Blood transfusion named as priority treatment for Ebola". Nature. Retrieved 11 September 2014.
- Jump up^ "Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease Empirical treatment during outbreaks". WHO. Retrieved 4 October 2014.
- ^ Jump up to:a b c d "Statement on the WHO Consultation on potential Ebola therapies and vaccines".WHO. 5 September 2014. Retrieved 1 October 2014.
- Jump up^ Mupapa K, Massamba M, Kibadi K, Kuvula K, Bwaka A, Kipasa M, Colebunders R, Muyembe-Tamfum JJ (1999). "Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee". J. Infect. Dis. 179 Suppl 1: S18–23. doi:10.1086/514298.PMID 9988160.
- Jump up^ Saphire EO (2013). "An update on the use of antibodies against the filoviruses".Immunotherapy 5 (11): 1221–33. doi:10.2217/imt.13.124. PMID 24188676.
- Jump up^ Gulland, A. (8 September 2014). "First Ebola treatment is approved by WHO". BMJ 349(sep08 7): g5539–g5539. doi:10.1136/bmj.g5539. PMID 25200068.
- Jump up^ Kroll, David (26 August 2014). "How will we know if the Ebola drugs worked?". Forbes. Retrieved 1 October 2014.
- Jump up^ Nathan Seppa (29 August 2014). "ZMapp drug fully protects monkeys against Ebola virus". Science News (Society for Science & the Public). Retrieved 1 October 2014.
- Jump up^ Oestereich L, Lüdtke A, Wurr S, Rieger T, Muñoz-Fontela C, Günther S (2014). "Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model". Antiviral Res. 105: 17–21. doi:10.1016/j.antiviral.2014.02.014.PMID 24583123.
- Jump up^ http://www.msn.com/en-gb/news/world/french-nurse-cured-of-ebola-contracted-in-liberia/ar-BB7r1UJ
- Jump up^ "BioCryst to Launch NHP Ebola Drug Safety, Efficacy Studies 'Within Weeks'. David Kroll, Forbes Magazine. 29 August 2014". Forbes. 29 August 2014. Retrieved 5 October 2014.
- Jump up^ "DURHAM: BioCryst receives additional funding for Ebola drug – WNCN: News, Weather". WNCN. 18 September 2014. Retrieved 5 October 2014.
- Jump up^ Chimerix experimental drug shows promise in fighting Ebola virus. WNCN News, 4 September 2014
- Jump up^ http://money.cnn.com/news/newsfeeds/articles/globenewswire/10101305.htm
- Jump up^ Geisbert TW, Lee AC, Robbins M, Geisbert JB, Honko AN, Sood V, Johnson JC, de Jong S, Tavakoli I, Judge A, Hensley LE, Maclachlan I (29 May 2010). "Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: A proof-of-concept study". The Lancet 375 (9729): 1896–1905. doi:10.1016/S0140-6736(10)60357-1. PMID 20511019.
- Jump up^ Warren TK, Warfield KL, Wells J, Swenson DL, Donner KS, Van Tongeren SA, Garza NL, Dong L, Mourich DV, Crumley S, Nichols DK, Iversen PL, Bavari S (September 2010). "Advanced antisense therapies for postexposure protection against lethal filovirus infections". Nature Medicine 16 (9): 991–994. doi:10.1038/nm.2202. PMID 20729866.
- Jump up^ Helen Branswell (3 August 2014). "Nancy Writebol, U.S. missionary, didn't get TKM-Ebola drug, Tekmira says". CBC News. Canadian Press.
- Jump up^ Heald AE, Iversen PL, Saoud JB, Sazani P, Charleston JS, Axtelle T, Wong M, Smith WB, Vutikullird A, Kaye E (25 August 2014). "Safety and pharmacokinetic profiles of phosphorodiamidate morpholino oligomers with activity against Ebola virus and Marburg virus: results of two single ascending dose studies". Antimicrobial Agents and Chemotherapy. doi:10.1128/AAC.03442-14. PMID 25155593.
- ^ Jump up to:a b Johansen LM, Brannan JM, Delos SE, Shoemaker CJ, Stossel A, Lear C, Hoffstrom BG, Dewald LE, Schornberg KL, Scully C, Lehár J, Hensley LE, White JM, Olinger GG (2013). "FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection". Sci Transl Med 5 (190): 190ra79. doi:10.1126/scitranslmed.3005471.PMC 3955358. PMID 23785035. Lay summary – Healthline Networks, Inc.
- Jump up^ Gehring G, Rohrmann K, Atenchong N, Mittler E, Becker S, Dahlmann F, Pöhlmann S, Vondran FW, David S, Manns MP, Ciesek S, von Hahn T (2014). "The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry". J. Antimicrob. Chemother. 69 (8): 2123–31. doi:10.1093/jac/dku091. PMID 24710028.
- Jump up^ Xu L, Sanchez A, Yang Z, Zaki SR, Nabel EG, Nichol ST, Nabel GJ (January 1998). "Immunization for Ebola virus infection". Nature Medicine 4 (1): 37–42. doi:10.1038/nm0198-037. PMID 9427604.
- ^ Jump up to:a b Sullivan NJ, Geisbert TW, Geisbert JB, Xu L, Yang ZY, Roederer M, Koup RA, Jahrling PB, Nabel GJ (7 August 2003). "Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates". Nature 424 (6949): 681–684. doi:10.1038/nature01876.PMID 12904795.
- Jump up^ Geisbert TW, Daddario-Dicaprio KM, Geisbert JB, Reed DS, Feldmann F, Grolla A, Ströher U, Fritz EA, Hensley LE, Jones SM, Feldmann H (9 December 2008). "Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses". Vaccine 26 (52): 6894–6900.doi:10.1016/j.vaccine.2008.09.082. PMC 3398796. PMID 18930776.
- Jump up^ Geisbert TW, Daddario-Dicaprio KM, Lewis MG, Geisbert JB, Grolla A, Leung A, Paragas J, Matthias L, Smith MA, Jones SM, Hensley LE, Feldmann H, Jahrling PB (November 2008). "Vesicular stomatitis virus-based Ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates". In Kawaoka, Yoshihiro. PLoS Pathogens 4(11): e1000225. doi:10.1371/journal.ppat.1000225. PMC 2582959. PMID 19043556.
- Jump up^ Geisbert TW, Geisbert JB, Leung A, Daddario-DiCaprio KM, Hensley LE, Grolla A, Feldmann H (2009). "Single-injection vaccine protects nonhuman primates against infection with Marburg virus and three species of Ebola virus". Journal of Virology 83 (14): 7296–7304. doi:10.1128/JVI.00561-09. PMC 2704787. PMID 19386702.
- Jump up^ Warfield KL, Swenson DL, Olinger GG, Kalina WV, Aman MJ, Bavari S (2007). "Ebola virus‐like particle–based vaccine protects nonhuman primates against lethal ebola virus challenge". The Journal of Infectious Diseases 196: S430–S437. doi:10.1086/520583.PMID 17940980.
- ^ Jump up to:a b Oplinger, Anne A. (2003-11-18). NIAID Ebola vaccine enters human trial. Bio-Medicine.
- ^ Jump up to:a b "Ebola/Marburg vaccine development" (Press release). National Institute of Allergy and Infectious Diseases. 15 September 2008.
- Jump up^ Martin JE, Sullivan NJ, Enama ME, Gordon IJ, Roederer M, Koup RA, Bailer RT, Chakrabarti BK, Bailey MA, Gomez PL, Andrews CA, Moodie Z, Gu L, Stein JA, Nabel GJ, Graham BS (November 2006). "A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial". Clinical and Vaccine Immunology 13 (11): 1267–1277.doi:10.1128/CVI.00162-06. PMC 1656552. PMID 16988008.
- Jump up^ Bush, L (21 April 2005). "Crucell and NIH sign Ebola vaccine manufacturing contract".Pharmaceutical Technology 29. p. 28.
- Jump up^ Jones SM, Feldmann H, Ströher U, Geisbert JB, Fernando L, Grolla A, Klenk HD, Sullivan NJ, Volchkov VE, Fritz EA, Daddario KM, Hensley LE, Jahrling PB, Geisbert TW (July 2005). "Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses". Nature Medicine 11 (7): 786–790. doi:10.1038/nm1258.PMID 15937495.
- Jump up^ "Viral Hemorrhagic Fever". Infectious Disease Emergencies. San Francisco Department of Public Health. Ribavirin Therapy. Retrieved 24 October 2014.
- Jump up^ Phoolcharoen W, Dye JM, Kilbourne J, Piensook K, Pratt WD, Arntzen CJ, Chen Q, Mason HS, Herbst-Kralovetz MM (2011). "A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge". Proc. Natl. Acad. Sci. U.S.A. 108 (51): 20695–700.Bibcode:2011PNAS..10820695P. doi:10.1073/pnas.1117715108. PMC 3251076.PMID 22143779. Lay summary – BBC News.
- Jump up^ "Canadian-made Ebola vaccine used after German lab accident". CBCNews (Canadian Broadcasting Corporation). Canadian Press. 20 March 2009. Retrieved 2 August 2014.
- Jump up^ Tuffs A (March 2009). "Experimental vaccine may have saved Hamburg scientist from Ebola fever". BMJ 338: b1223. doi:10.1136/bmj.b1223. PMID 19307268.
- Jump up^ Feldmann H, Jones SM, Daddario-DiCaprio KM, Geisbert JB, Ströher U, Grolla A, Bray M, Fritz EA, Fernando L, Feldmann F, Hensley LE, Geisbert TW (January 2007). "Effective post-exposure treatment of Ebola infection". PLoS Pathogens 3 (1): e2.doi:10.1371/journal.ppat.0030002. PMC 1779298. PMID 17238284.
- Jump up^ Geisbert TW, Daddario-DiCaprio KM, Williams KJ, Geisbert JB, Leung A, Feldmann F, Hensley LE, Feldmann H, Jones SM (June 2008). "Recombinant vesicular stomatitis virus vector mediates postexposure protection against Sudan Ebola hemorrhagic fever in nonhuman primates". Journal of Virology 82 (11): 5664–5668. doi:10.1128/JVI.00456-08. PMC 2395203. PMID 18385248.
- ^ Jump up to:a b c "Experimental Ebola Vaccine Processed in Maryland". Drug Discov. Dev. Associated Press. 2 October 2014.
- Jump up^ "First British volunteer injected with trial Ebola vaccine in Oxford". Guardian. 17 September 2014. Retrieved 17 September 2014.
- Jump up^ "An Ebola vaccine was given to 10 volunteers, and there are 'no red flags' yet". Washington Post. 16 September 2014. Retrieved 17 September 2014.
- Klenk, Hans-Dieter (January 1999). Marburg and Ebola Viruses (Current Topics in Microbiology and Immunology). Berlin: Springer-Verlag Telos. ISBN 978-3-540-64729-4.
- Klenk, Hans-Dieter; Feldmann, Heinz (2004). Ebola and Marburg viruses: molecular and cellular biology (Limited preview). Wymondham, Norfolk, UK: Horizon Bioscience. ISBN 978-0-9545232-3-7.
- Kuhn, Jens H. (2008). Filoviruses: A Compendium of 40 Years of Epidemiological, Clinical, and Laboratory Studies. Archives of Virology Supplement, vol. 20 (Limited preview). Vienna: SpringerWienNewYork. ISBN 978-3-211-20670-6.
- McCormick, Joseph; Fisher-Hoch, Susan (June 1999) [1996]. Level 4: Virus Hunters of the CDC (Limited preview). Horvitz, Leslie Alan (Updated [3rd] ed.). Barnes & Noble. ISBN 978-0-7607-1208-5.
- Pattyn, S. R. (1978). Ebola Virus Haemorrhagic Fever (Full free text) (1st ed.). Amsterdam: Elsevier/North-Holland Biomedical Press. ISBN 0-444-80060-3.
- Ryabchikova, Elena I.; Price, Barbara B. (2004). Ebola and Marburg Viruses: A View of Infection Using Electron Microscopy. Columbus, Ohio: Battelle Press. ISBN 978-1-57477-131-2.
External links
|Find more about Ebola virus diseaseat Wikipedia's sister projects
|Definitions from Wiktionary
|Media from Commons
|News stories from Wikinews
|Database entry Q51993 on Wikidata
- Ebola virus disease at DMOZ
- CDC: Ebola hemorrhagic fever – Centers for Disease Control and Prevention, Special Pathogens Branch
- WHO: Ebola haemorrhagic fever – World Health Organization, Global Alert and Response
- Google Map of Ebola Outbreaks
- WHO recommended infection control measures


text:
Natasha and Matt's Engagement Session | Seaport and Boston Proper, MA/
My time with Natasha and Matt was absolutely breathtaking, with a beautiful couple and beautiful light the ENTIRE time! From western mass to Boston, these two had been together for five wonderful years when Mike popped the question at Nobska light. They love the cape so much, they are having their September wedding at Popponessett Inn and I'm already excited for it! Congratulations you two!
Hair: Blo Seaport

subset: commoncrawl


text:
Sidewalk Obstruction/Repair Request at 331 Newton St, Brookline
Closed about 2 years ago via iPhone
The trees need to be trimmed up as you don't have to duck on the side walk. The is the water authority.
request #: 15825status: Closed. Thank you for using the BrookONline Notify Application. The work will be completed within seven days.
submitted: Wed Jun 07, 2017 05:47PM
opened: Wed Jun 07, 2017 05:47PM
closed: Thu Jul 13, 2017 10:51AM


text:
As we move into a more flexible technological working age, it's now common practice for workplaces to allow employees to Bring Your Own Device (dubbed BYOD) to work.
BYOD allows employees to work on the device they choose, providing key benefits including cost savings, increased employee satisfaction (due to mobility and flexibility) and increased productivity levels.
However, despite the clear advantages of a BYOD workplace, there are potential costs and risks to an organisation in allowing corporate data to be accessed on personal devices.
In BYOD investigations we've worked on, if BYOD is not regulated properly, it can threaten IT security and compromise valuable company data.
Employers should ask themselves what security measures are in place if the device gets lost or stolen. Do other people (i.e. children or family members) have access to the device?
And whilst an employee can 'wipe' a device clean (if they are disposing the device), have all the files been deleted? In some cases, sensitive data can be recovered.
For employers who are intent on taking this seriously, they should implement a BYOD policy and adopt a system that works best for an organisations own circumstances. An effective BYOD solution will enable you to secure the data, not just the device.
Implementing a BYOD policy
• Allow employees to choose their own device - Provide the employee with their choice of device for enhanced efficiency and morale, but allow IT departments to maintain control over the device and rights to access work-related information, if necessary.
• Increase IT controls - Network security is paramount. Implementing mobile application management (MAM) to personal devices allows management of critical work-related applications and the ability to remotely lock or wipe that content. Particularly in the case of sophisticated malware and mobile Trojan attacks. Other policies could include encrypting sensitive data and/or limiting corporate access to sensitive areas.
• Mandatory training for staff using BYOD - Provide training about the associated risks with inadvertently sharing corporate information to reduce the likelihood of corporate information being leaked (e.g. correct backups, wiping devices prior to disposal)
• Strictly enforce breaches of policy - This will act as a warning to otherwise complacent employees and to help create a compliant environment.
BYOD is about being innovative and helping employees to work better, it's part of a growing trend that helps empower workforces.
But it's important that employers do their due diligence to evaluate the opportunities versus the risks of employees using personal devices at work - because one of the most potentially catastrophic risks is not having any sort of BYOD policy in place at all.
David Webb is the NZ Managing Partner of PPB Advisory


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Cat pee anyplace in the house could make your entire home smell like a litter box. Cats' urine incorporates robust-smelling proteins they use to mark their territory, a scent that is almost unattainable to get rid of. Cleansing it could actually typically wet the crystallized proteins and reactivate the odor. It can be upsetting and very demanding. Nice tips for detecting smoke! Eliminating that odor is so pricey, and too many sellers attempt to masks it and fool patrons. Hello guys! In case you missed it, please see yesterday's put up and depart us some suggestions to assist us make StyleMutt merely amazing! There are 4 opportunities left to obtain a special reward for commenting and we'd actually, (reeeaaallllyyy), respect your input.
Everybody who lives in the home ought to follow proper safety protocol. You can have one of the best security set up within the neighbourhood, and it may be let down by somebody leaving the front door open by mistake. Bear in mind to lock doors, garages, shut windows, set alarms and every part else that needs doing earlier than leaving the home. Go through a guidelines day-after-day in the event you should till it turns into routine. It is higher than leaving the house and also you're midway to work and also you suppose you might have left a door unlocked, and then spending the rest of the day worrying about it. It is even worse for those who don't fret, as a result of that signifies conceitedness, complacency, and nonchalance, which is a harmful angle to have in a crime-filled country. As a result of that's what the thieves are relying on in the end.
When I was preteen I had a good friend with an underground house and I so cherished it. It was not boxed in like yours however one entire side, the size was open however except you went over the little knoll to the again you didn't know the house was there! It seemed out onto an enormous subject and then woods and deer grazed there typically. Arrive early. If the haunting will last for several hours, be sure you have a plan for relieving actors so they can take a break.
I can almost hear the objections now. I've seen the suggestion that people simply don't strive hard enough to stay clear and nicely groomed. But ponder this – do you truthfully think that you may show up to a job interview with a tidy haircut, a pressed swimsuit and tie, shined sneakers, a bathe fresh scent and a clean shave with no barber, a toilet, an iron and a closet? For ladies it's also sophisticated by social necessities to wear make-up to an interview.
Well, in keeping true to Flamingo Friday, I wished to share our beautiful watercolor flamingo that's still our #1 finest vendor, day after day increasingly people purchase this print. I'm so blissful it's been such a success as a result of it's SO beautiful and that means folks around the globe share in the same completely happy wall artwork as me.


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I had quite a year on the road in 2008
I had quite a year on the road in 2008.
My band (Matt Fries, Keith Hall, Cliff Schmitt and John Sneider) and I performed at Hampton Court Palace (Henry the VIII's summer palace) with British jazz royalty: Dame Cleo Laine and Sir John Dankworth. We did two concert hall and festival tours of Germany. We also played in Paris, Vienna, Norway, Denmark and Northern Ireland. We returned to three legendary jazz clubs: London's Ronnie Scott's, The Copenhagen Jazz House, and The Blue Note in New York City. In the US we played Annapolis, Boston, Boise, Hartford, Vail, Denver and several dates in North Carolina.
I did some shows without my band as well. I sang in Dublin with the RTE Concert Orchestra. I performed in a concert of John Lennon songs with The Liverpool Philharmonic and jazz singer Claire Martin and actor/singer Mark McGann. I appeared in Berlin in an open-air orchestral concert with trumpet star Til Bronner, The New York Voices and superstar baritone, Thomas Quastoff. I sang a song at an all-star 75th birthday concert for Quincy Jones at the Montreux Jazz Festival, rubbing elbows with Chaka Khan, Al Jarreau, James Moody, Mick Hucknall, Nana Mouskouri, Herbie Hancock, Petula Clark, Billy Cobham, Lee Ritenour, Joe Sample, Toots Thielemans, and more.
At home in Idaho I did my best to be a good citizen. I played at a fundraiser for a great environmental group called the Idaho Conservation League, with my good friends and collaborators, Bill Coffey and Ned Evett. I produced and performed a solo acoustic concert to benefit The Ada County Democrats and raised over $20,000 to fund their Get Out The Vote initiative. We even managed to send an Idaho Democrat to Congress, for the first time in decades. And, for the third year in a row, I co-produced The Xtreme Holiday Xtravaganza, a rollicking, anything-goes holiday variety show with an all-star cast of Idaho's finest musicians, comedians and dancers, all to raise funds for Interfaith Sanctuary, a Boise shelter for the homeless. We raised nearly $20,000 and boosted awareness and volunteer support for the shelter.
Then I slept. And slept.
When I awoke I got back to work on my next record. I've been writing songs, working on arrangements and planning the recording. I expect the new album will be out by early Autumn. (OK, I've been doing a lot of skiing, too.)


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Heidi Caroll
John Dickinson High Class of 1997
Memories of Heidi Caroll
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text:
Report by Sharjeel Nasir, Tarbiyyat Secertary Nottingham Jamaat
Report of Tarbiyyat Day, Nottingham: 29th March, 2015
The first Nottingham tarbiyyat programme was arranged on 29th Mar 2015. The programme started at 11:28 with recitation of Holy Quran by respected Jazib Amir Dar Shb from atfalul Ahmadiyya Nottingham. Nisar Orchard Shb, the Tarbiyyat Secretary UK, requested Sec. Tarbiyyat Nottingham to announce brief plan of the day. At that time, we had total of 9 members.
Secretary Shb Tarbiyyat introduced himself and interacted with the people present on the day and equally engaged Lajna members in another room.
Secretary Shb kicked off by asking what Tarbiyyat is and enquired some feedback from the audience. Secretary Shb asked few members about who the Sadr jamaat and Local Secretary Tarbiyyat are. Members engaged and provided answers.
He continued and talked about;
• Regular Tarbiyyat Activity in Local Jamaat
• Why Tarbiyyat is important
• That he is ready to come at any event
• The gap between office bearers and members of jamaat
• That aamla members perhaps do not do any work
• How to work together as a one jamaat
• Discuss about Tarbiyyat issues
• Hold Local Events like Jalsa Musleh maood, Masih-e-Maood Day and Jalsa Seerat-un-nabi
• Attendance for Fajr Salaat is very poor
• Importance of Congregational Prayer
• Discusses whether there is need for Tarbiyyat at a burial, or Marriage, mosque antiquates
• There are many thinks to talk about in terms of Tarbiyyat
• Developing Moral values
Secretary Shb continued and constantly engaged with both gents and ladies.
The open discussion about 'What we want from Life' was very much educating for members of Jama'at. The moral virtues and their importance in our life were also discussed.
Education, Employment, Family, Status
There are two ways of looking at this.
Education: you can show superiority to others, but it's better to share your education with others. Naiki
Employment: Greed to work/make money – Sagawat, Give more as you earn more
Family: every member of household is busy doing his/her own thing – Do things together as a family – Mutahhid
Status: Takabar/Gharoor – you can increase in Aajzi
To become better person and gain qualities, you just need the will to do this. Example: patience, humbleness, obedience, etc. They are all free and just require your will to gain there qualities.
We broke us for Zohr Prayer and Secretary Shb emphasized that it is becoming a habit of combining a prayers together. This is not the way to do it. Juzoor mentioned that very often in his sermons.
We had lunch where all members enjoyed the food and briefly touched upon the arrangement of local events.
After lunch at 14:15pm, we got together and joined for a quiz competition between the two teams. Youngsters were very keen to answer the questions asked by Secretary Shb and on lajna side, there were also two teams formed.
Secretary Shb thanked everyone who came on the day and hoped to see more members for future events. He then led all attendees into silent prayer.
Members greeted and showed happiness for a successful event and hoped to see secretary Shb soon in the near future.
At the final sessions we had a total of 35 members.
Feedback from jamaat members:
Members felt that Secretary Shb was well prepared and engaged to every members as they came in. There was no boredom among atfal and youngsters. All members had a joyful day.


text: With all that is wrong world wide today, I am surprised we haven't killed each other off yet. I say that with all the trouble in the Middle East and elsewhere sure points to the end times as we know it. I am not sure anymore what to think of but I can say this that I am ready in case it comes to past, I know it will but when is another matter that only my Higher Power knows. I am confident than I will see this come to past and will see my rewards that are waiting for me. It's just a matter of time.


text:
Best Time to Visit – Etosha NP
The best time to visit Etosha National Park is during the dry winter months from July to October. Less water is available during this time and the animals tend to gather around the few sources that are available. The Wet season (November to April) is less productive for spotting wildlife because the animals tend to move around more.
May to October –Dry Season – Winter
- Best time for wildlife viewing with large numbers of animals at waterholes
- Weather is good, although October is very hot
- July to September is high season and it gets very busy
- The sky is filled with dust and it can be hazy
Wildlife Photos
November to April –Wet Season – Summer
- The rainfall comes as a relief, although it rarely rains for long
- Landscape is attractive and skies are clear
- Wildlife is in peak condition and plenty of babies can be seen
- Prime birding during the migrant season
- Animals are dispersed making viewing difficult
- It tends to be very hot
Wildlife Photos
Best Time to go to Namibia by Major Park
Etosha National ParkJanFebMarAprMayJunJulAugSepOctNovDec


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Staff Report
Flydubai on July 22 launched a special summer offer for families where children accompanied by their parents can fly from Dh10 plus taxes and surcharges to select destinations on the flydubai network.
The "kids fly for less" offer will be available for booking from Thursday 19 July to Saturday 28 July. The special promotion is applicable on adult return fares in Economy Class for travel between 19 July and 15 August without any blackout dates and the accompanying child can fly from Dh10.
Families wishing to travel with their children this summer can benefit from the promotional fares and book an exciting holiday to one of the following flydubai destinations including Baku, Batumi, Catania, Gabala, Tbilisi, Yerevan and Zanzibar.
The offer is also available for packages purchased to the above destinations through the Holidays by flydubai portal.
Recently flydubai launched a "Surf and drive" offer where passengers can enjoy unlimited connectivity for only USD 08 per flight and have the chance to win one of two new Toyota Rush SUVs.
The promotion is available on all flydubai WiFi enabled aircraft until 30 September 2018. To enter the draw, passengers can simply purchase a WiFi package on board a flydubai flight and their details will be automatically enrolled. – email@example.com