However, on 31 August 2021, the WHO found that, after further tests in a laboratory in  Lyon , the patient did not have Ebola. The cause of her disease is still being analyzed. [ 248 ]


On 23 April 2022, a case of Ebola was confirmed in the DRC in the Equateur province. The case was a 31-year-old man whose symptoms began on 5 April, but did not seek treatment for over a week. On 21 April, he was admitted to an Ebola treatment centre and died later that day. [ 249 ]  By 24 May 2022, there were 5 recorded deaths in the DRC. [ 250 ]  On 15 August, the fifth case was buried, and the outbreak was declared over, 42 days after, on 4 July 2022. [ 251 ]


In September 2022,  Uganda reported 7 cases infected with the Ebola Sudan strain , [ 252 ]  but by mid-October the count had increased to 63. [ 253 ]
In November 2022, the outbreak in Uganda continued - still without a vaccine. [ 4 ]  On 10 January 2023, the outbreak was considered over after no new cases had been reported for 42 days; the outbreak killed nearly 80 people. [ 254 ]


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. [ 96 ] [ 255 ]  It has the potential to be weaponised for use in  biological warfare , [ 256 ] [ 257 ]  and was investigated by  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. [ 258 ]  Fake emails pretending to be Ebola information from the WHO or the Mexican government have, in 2014, been misused to spread computer malware. [ 259 ]  The BBC reported in 2015 that "North Korean state media has suggested the disease was created by the U.S. military as a biological weapon." [ 260 ]


Richard Preston 's 1995  best-selling  book,  The Hot Zone , dramatised the Ebola outbreak in Reston, Virginia. [ 261 ] [ 262 ] [ 263 ]


William Close 's 1995  Ebola: A Documentary Novel of Its First Explosion [ 264 ] [ 265 ]  and 2002  Ebola: Through the Eyes of the People  focused on individuals' reactions to the 1976 Ebola outbreak in Zaire. [ 266 ] [ 267 ]


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 ). [ 268 ] [ 269 ]


As the Ebola virus epidemic in West Africa developed in 2014, a number of popular self-published and well-reviewed books containing sensational and misleading information about the disease appeared in electronic and printed formats. The authors of some such books admitted that they lacked medical credentials and were not technically qualified to give medical advice. The World Health Organization and the United Nations stated that such misinformation had contributed to the spread of the disease. [ 270 ]


Ebola has a high mortality rate among primates. [ 271 ]  Frequent outbreaks of Ebola may have resulted in the deaths of 5,000 gorillas. [ 272 ]  Outbreaks of Ebola may have been responsible for an 88% decline in tracking indices of observed chimpanzee populations in the 420 km 2  Lossi Sanctuary between 2002 and 2003. [ 273 ]  Transmission among chimpanzees through meat consumption constitutes a significant risk factor, whereas contact between the animals, such as touching dead bodies and grooming, is not. [ 274 ]


Recovered gorilla carcasses have contained multiple Ebola virus strains, suggesting 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 that transmission among gorilla groups is unlikely, and that outbreaks result from transmission between viral reservoirs and animal populations. [ 273 ]


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. [ 86 ] [ 275 ]


Dogs may become infected with EBOV but not develop symptoms. Dogs in some parts of Africa  scavenge  for food, and they sometimes eat EBOV-infected animals and also the corpses of humans. A 2005 survey of dogs during an EBOV outbreak found that although they remain asymptomatic, about 32 percent of dogs closest to an outbreak showed a  seroprevalence  for EBOV versus nine percent of those farther away. [ 276 ]  The authors concluded that there were "potential implications for preventing and controlling human outbreaks."


In late 1989, Hazelton Research Products' Reston Quarantine Unit in  Reston, Virginia , had an outbreak of fatal illness amongst certain lab monkeys. This lab outbreak was initially diagnosed as  simian haemorrhagic fever virus  (SHFV) and occurred amongst a shipment of  crab-eating macaque  monkeys imported from the Philippines. Hazelton's veterinary pathologist in Reston sent tissue samples from dead animals to the  United States Army Medical Research Institute of Infectious Diseases  (USAMRIID) at  Fort Detrick, Maryland , where an  ELISA  test indicated the antibodies present in the tissue were a response to Ebola virus and not SHFV. [ 277 ]  An electron microscopist from USAMRIID discovered  filoviruses  similar in appearance, in crystalloid aggregates and as single filaments with a shepherd's hook, to Ebola in the tissue samples sent from Hazelton Research Products' Reston Quarantine Unit. [ 278 ]


A  US Army  team headquartered at USAMRIID  euthanised  the surviving monkeys, and brought all the dead monkeys to Fort Detrick for study by the Army's veterinary pathologists and virologists, and eventual disposal under safe conditions. [ 277 ]  Blood samples were taken from 178 animal handlers during the incident. [ 279 ]  Of those, six animal handlers eventually  seroconverted , including one who had cut himself with a bloody scalpel. [ 97 ] [ 280 ]  Despite its status as a  Level‑4  organism and its apparent  pathogenicity  in monkeys, when the handlers did not become ill, the CDC concluded that the virus had a very low pathogenicity to humans. [ 280 ] [ 281 ]


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  (RESTV) after the location of the incident. [ 277 ]  Reston virus (RESTV) can be transmitted to pigs. [ 86 ]  Since the initial outbreak it has since been found in nonhuman  primates  in Pennsylvania, Texas, and Italy, [ 282 ]  where the virus had infected pigs. [ 283 ]  According to the WHO, routine cleaning and disinfection of pig (or monkey) farms with  sodium hypochlorite  or  detergents  should be effective in inactivating the  Reston ebolavirus . Pigs that have been infected with RESTV tend to show  symptoms  of the disease. [ 284 ]


As of July 2015 [update] , no medication has been proven safe and effective for treating Ebola. By the time the  Ebola virus epidemic in West Africa  began in 2013, there were at least nine different candidate treatments. Several trials were conducted in late 2014, and early 2015, but some were abandoned due to lack of efficacy or lack of people to study. [ 285 ]


As of August 2019 [update] , two experimental treatments known as  atoltivimab/maftivimab/odesivimab  and  ansuvimab  were found to be 90% effective. [ 286 ] [ 287 ] [ 288 ]


The diagnostic tests currently available require specialised equipment and highly trained personnel. Since there are few suitable testing centres in West Africa, this leads to delay in diagnosis. [ 289 ]


On 29 November 2014, a new 15-minute Ebola test was reported that if successful, "not only gives patients a better chance of survival, but it prevents transmission of the virus to other people." The new equipment, about the size of a laptop and solar-powered, allows testing to be done in remote areas. [ 290 ]


On 29 December 2014, the U.S.  Food and Drug Administration  (FDA) approved the LightMix Ebola Zaire  rRT-PCR  test for patients with symptoms of Ebola. [ 291 ]


Animal models and in particular non-human primates are being used to study different aspects of Ebola virus disease. Developments in  organ-on-a-chip  technology have led to a chip-based model for Ebola haemorrhagic syndrome. [ 292 ]


This  list of Ebola outbreaks  records the known occurrences of  Ebola virus disease , a highly infectious and acutely lethal  viral  disease that has afflicted humans and animals primarily in  equatorial Africa . [ 1 ]  The  pathogens  responsible for the disease are the five  ebolaviruses  recognized by the  International Committee on Taxonomy of Viruses :  Ebola virus  (EBOV),  Sudan virus  (SUDV),  Reston virus  (RESTV),  Taï Forest virus  (TAFV), and  Bundibugyo virus  (BDBV). [ 2 ] [ 3 ] [ 4 ] [ 5 ]  Four of the five  variants  have caused the disease in humans as well as other animals; RESTV has caused clinical symptoms only in non-human  primates . [ 6 ] [ 7 ]  RESTV has caused  subclinical  infections in humans, producing an  antibody  response but no visual symptoms or disease state manifestations. [ 8 ]


Transmission of the  ebolaviruses  between  natural reservoirs  and humans is rare, and outbreaks of Ebola virus disease are often traceable to a  single case  where an individual has handled the carcass of a  gorilla ,  chimpanzee ,  bats , [ 9 ]  or  duiker . [ 10 ]  The virus then spreads person-to-person, especially within families, in hospitals, and during some  mortuary   rituals  where contact among individuals becomes more likely. [ 11 ]


Learning from failed responses, such as during the 2000 outbreak in  Uganda , the  World Health Organization  (WHO) established its  Global Outbreak Alert and Response Network , and other  public health  measures were instituted in areas at high risk. Field laboratories were established to confirm cases, instead of shipping samples to  South Africa . [ 12 ]  Outbreaks are also closely monitored by the United States  Centers for Disease Control and Prevention  (CDC) Special Pathogens Branch. [ 13 ]


Nigeria  was the first country in  western Africa  to successfully curtail the virus, and its procedures have served as a model for other countries to follow. [ 14 ] [ 15 ] [ 16 ]


The information in the following tables comes from the  World Health Organization  (WHO). This data excludes all laboratory personnel cases,  Reston virus  cases (since they are all  asymptomatic ), and suspected cases. [ 17 ]  For a complete overview, those cases are included below with footnotes and supporting sources.


The last strain Occurred in the  Booué  area with transport of patients to  Libreville . The index case-patient was a hunter who lived in a  forest timber camp . The disease was spread by close contact with infected persons. A dead chimpanzee found in the forest at the time was determined to be infected. [ 21 ]


The second strain Occurred in the districts of  Mbomo  and  Kelle  in the  Cuvette-Ouest Department . [ 26 ]


The third strain Occurred in Mbomo and Mbandza villages, located in Mbomo District in the Cuvette-Ouest Department. [ 27 ]


On 8 May 2018, the government of the  Democratic Republic of the Congo  reported two confirmed cases of Ebola infection in the northwestern town of  Bikoro . [ 43 ]  On 17 May, a case was confirmed in the city of  Mbandaka . [ 44 ]  Health authorities were planning to  ring vaccinate  with  rVSV-ZEBOV , a recently developed experimental  Ebola vaccine , to contain the outbreak. [ 44 ] [ 45 ]  The outbreak was ongoing as of 24 June 2018, in 2014 a different area of Equateur province was affected [ 46 ] [ 47 ]
On 24 July 2018 the outbreak was declared over. [ 48 ] [ 49 ] [ 50 ] [ 51 ]


On 1 August 2018, the  Democratic Republic of the Congo  Ministry of Health declared an outbreak when 4 individuals tested positive for the Ebola virus. [ 54 ] [ 55 ] [ 56 ] [ 57 ]  On 11 June 2019, the WHO confirmed that a five-year-old boy in Uganda died after being diagnosed with Ebola. [ 58 ] [ 59 ]  On 25 June 2020, the second biggest EVD outbreak ever was declared over. [ 60 ]


By 18 November 2020, the World Health Organization and the Congolese government had not received reports of any cases of Ebola in Équateur province or all of the DRC for 42 days. [ 65 ]  When the outbreak was declared over, there were 130 reported cases and 55 reported fatalities due to the virus. [ 66 ]


On 11 May 2017, the  Ministry of Public Health for the Democratic Republic of the Congo  notified the WHO of an Ebola outbreak in the Likati health zone (LHZ) in  Bas-Uele  province, in the northern part of the country. Suspected infections were reported from Nambwa, Mouma, and Ngay. The LHZ borders the  Central African Republic , which made this outbreak a moderate risk to the region. [ 95 ] [ 96 ]


First time Marburg virus disease was detected in the country.


The  2018 Équateur province Ebola outbreak  occurred in the north-west of the  Democratic Republic of the Congo  (DRC) from May to July 2018. It was contained entirely within  Équateur province , and was the first time that vaccination with the  rVSV-ZEBOV  Ebola vaccine had been attempted in the early stages of an Ebola outbreak, [ 6 ]  with a total of 3,481 people vaccinated. [ 7 ] [ 8 ] [ 9 ]  It was the ninth recorded Ebola outbreak in the DRC. [ 7 ]


The outbreak began on 8 May 2018, when it was reported that 17 people were suspected of having died from EVD near the town of  Bikoro  in the  Province of Équateur . [ 10 ]  The  World Health Organization  declared the outbreak after two people were confirmed as having the disease. [ 1 ] [ 11 ]  On 17 May, the virus was confirmed to have spread to the  inland port  city of  Mbandaka , causing the WHO to raise its assessment of the national risk level to "very high", [ 12 ] [ 13 ]  but not yet to constitute an  international public health emergency . [ 14 ]  The WHO declared the outbreak over on 24 July 2018, with 33 confirmed deaths. [ 15 ] [ 16 ] [ 3 ]


Subsequent to the end of this outbreak, the  Kivu Ebola epidemic  commenced in the eastern region of the country on 1 August 2018; [ 17 ]  it was declared over on 25 June 2020 with 2,280 deaths recorded. [ 18 ]  A further separate outbreak in the  Province of Équateur  was announced on 1 June 2020 by the Congolese health ministry, described as the eleventh Ebola outbreak since records began. [ 19 ]  This eleventh outbreak was declared over as of 18 November following no reported cases for 42 days, [ 20 ]  having caused 130 cases and 55 deaths. [ 21 ]


The earliest cases are believed to have occurred in early April 2018. [ 6 ]  The suspected  index case  was a police officer, who died in a health center in the village of  Ikoko-Impenge , near the market town of  Bikoro  in Équateur province, according to the  International Federation of the Red Cross and Red Crescent Societies . [ 22 ]


After his funeral, eleven family members became ill, and seven of them died. All of the seven deceased had attended the man's funeral or cared for him while he was sick. [ 22 ]  The identification of this individual as the index case has not yet been confirmed. [ 23 ]


Équateur province's Provincial Health Division reported 21 cases with symptoms consistent with  Ebola virus disease , of whom 17 had died, on 3 May 2018. [ 24 ]  Of these, eight cases were subsequently  shown not to have been Ebola-related. [ 25 ]  The outbreak was declared on 8 May after samples from two of five patients in Bikoro tested positive for the  Zaire strain  of the Ebola virus. [ 1 ] [ 24 ] [ 10 ]


On 10 May, the World Health Organization (WHO) stated that the Democratic Republic of the Congo had a total of 32 cases of EVD, [ 2 ]  and a further two suspected cases were announced on the following day, bringing the total cases to 34, all located in the Bikoro area of DRC. [ 26 ]


*  numbers are subject to revision both up, when new cases are discovered, and down, when tests show cases were not Ebola-related.


In the eight previous Ebola outbreaks in DRC since 1976, the virus had never before reached a major city. In May 2018, for the first time, four cases were confirmed in the city of Mbandaka. [ 41 ] [ 25 ]


On 14 May, suspected cases were reported in the  Iboko  and  Wangata  areas in  Équateur province , in addition to Bikoro. The WHO reported on 17 May 2018 that the first case of this outbreak in an urban area [ 22 ]  had been confirmed in the Wangata district of Mbandaka city, the capital of Équateur province, about 100 miles north of Bikoro. [ 22 ] [ 29 ] [ 12 ]   Mbandaka is a busy, densely populated port on the  Congo River  with a population of 1.2 million, [ 42 ]  leading to a high risk of contagion. [ 24 ] [ 22 ]  The following day, the WHO raised the health risk in DRC to "very high" due to the presence of the virus in an urban area. [ 13 ]


The DRC government was particularly concerned about the virus spreading by boat transport along the Congo between Mbandaka and the capital,  Kinshasa . [ 43 ]  The WHO also considered that there was a high risk of the outbreak spreading to nine other countries in the region, [ 24 ]  including the bordering  Republic of the Congo  and  Central African Republic . [ 43 ] [ 42 ]


As of 23 May 2018 [update] , the focus of the outbreak was split between Bikoro and Iboko; Iboko had 55% of the confirmed cases of EVD [ 25 ]  and Bikoro had 81.5% of the fatalities. [ 23 ]  The cases in the Bikoro health zone were located in  Ikoko Impenge  (12), Bikoro (6),  Momboyo  (1) and Moheli (1); those in the Iboko health zone were located in Itipo (13), Mpangi (2), Wenga (1) and Loongo (1). [ 25 ]


According to the fifth situation report released by the WHO, the  case fatality rate  (CFR) was 42.3%. [ 25 ]  Demographics had been reported for 44 cases as of 22 May; there were 26 cases of EVD in men and 18 in women; 7 cases were in children 14 years and under, and 9 were in those over 60 years. [ 25 ]   By 23 May, there had been 5 reported cases in health-care workers, including two who died. [ 25 ]   Contact tracing  was being employed to identify contacts with infected individuals. [ 23 ] [ 44 ]  On 29 May, it was reported that 800 contacts had been identified in the city of Mbandaka; [ 45 ]  the next day it was reported that 500 people in the city had been vaccinated. [ 46 ]


On 29 May, the WHO indicated that nine neighbouring countries had been alerted for being at high risk of spread of EVD, [ 47 ]  On 4 June, it was reported that Angola had closed its border with the DRC due to the outbreak. [ 48 ]


This outbreak in the Democratic Republic of the Congo was declared over on 24 July 2018 after 42 days passed without any new confirmed cases. [ 49 ] [ 16 ] [ 41 ]  Although it was noted that a new outbreak occurred only one week later in the eastern region of  Kivu ;   and it has  been established that they are not linked. [ 17 ]


The Bikoro area had three hospitals, but the area's health services were described by WHO as predominantly having "limited functionality"; [ 24 ]  they received supplies from international bodies but experienced frequent shortages. More than half of the Bikoro area cases were in  Ikoko-Impenge , a village not connected to the road system. [ 24 ] [ 25 ]  Bikoro lies in dense  rain forest , [ 22 ]  and the area's remoteness and inadequate infrastructure hindered treatment of EVD patients, as well as surveillance and vaccination efforts. [ 42 ]


Adherence was another challenge: on 20–21 May, three individuals with EVD in an isolation ward of a treatment center in  Mbandaka  fled; two later died after attending a prayer meeting, at which they may have exposed 50 other attendees to the virus. [ 50 ] [ 51 ] [ 52 ] [ 53 ]
 Bushmeat  was believed to be one vector of infection, but bushmeat vendors at the Mbandaka market told reporters that they did not believe Ebola was real or serious. [ 54 ]  Hostility towards health workers trying to offer medical assistance was also reported. [ 55 ]  On 29 May, the WHO forecast that there would be 100–300 cases by the end of July. [ 56 ]


Zaire ebolavirus , which was identified in this outbreak, [ 24 ]  is included in genus  Ebolavirus , family  Filoviridae , [ 57 ]


The virus was named for the  Ebola River , which runs as a tributary of the  Congo River  in the Democratic Republic of the Congo; the  Zaire strain  was first identified in 1976 in  Yambuku . [ 58 ] [ 59 ]


Médecins Sans Frontières  (MSF) established treatment centers in Bikoro, Ikoko and Wangata. [ 25 ]  WHO sent an expert team to Bikoro on 8 May, [ 1 ]  and on 13 May, WHO Director-General  Tedros Adhanom Ghebreyesus  visited the town. [ 60 ]  On 18 May, the WHO IHR committee met and decided against declaring a  Public Health Emergency of International Concern . [ 42 ]  As of 24 May 2018 [update] , WHO had sent 138 technical personnel to the three affected areas; the Red Cross  sent more than 150 people, and  UNICEF  personnel were also active. [ 25 ]  Other international agencies sending teams included the UK Public Health Rapid Support Team [ 61 ]  and the Africa Centres for Disease Control and Prevention. [ 62 ]  The  Wellcome Trust   donated £2 million towards the DRC outbreak. [ 63 ]   Merck  donated its experimental vaccine and the  GAVI  international vaccination alliance helped to support vaccination operations. [ 64 ]  Several tons of supplies were shipped to the DRC, including protection and disinfection kits and palliative drugs. [ 22 ]  After the virus spread to the city of Mbandaka, DRC health minister  Oly Ilunga Kalenga  announced that healthcare would be provided free for those affected. [ 65 ] [ 66 ]


US President  Donald Trump  has advocated rescinding Ebola funding and most financing for State Department emergency responses. National Security Advisor  John Bolton  removed the National Security Council's health security chief on the day that the Ebola outbreak was declared, shutting down the entire epidemic prevention office. [ 67 ]  The U.S.  Centers for Disease Control and Prevention  says "about five" of its staff advise the Congolese government. CDC presence appears to be smaller than West African countries'. The U.S.  Agency for International Development  promised $1 million to WHO for Ebola efforts. Germany has promised $5.8 million. [ 67 ]


Surveillance of travelers at Mbandaka's port and airport was performed. [ 24 ]  The DRC Ministry of Public Health identified 115 areas where movement of people increased the risk of virus transmission, including 83 river ports, nine airports and seven bus stations, as well as 16 markets. [ 23 ]   José Makila , the DRC minister of transport,  stated that the  Navy  would be used to surveil river traffic on the Congo. [ 43 ]  On 10 May, the  Nigerian Ministry of Health  reported it would start screening at its borders, [ 68 ]  and on 18 May 2018, a total of 20 countries had instituted screening of travelers coming from the DRC. [ 24 ]  WHO sent teams to 8/9 of the neighboring countries to assess their capability to deal with EVD spread and facilitate their surveillance. [ 25 ]  The DRC Ministry of Public Health worked with surveyors and cartographers from  UCLA  and OpenStreetMap DRC to improve mapping of the affected area. [ 69 ]  A laboratory commenced operations in Bikoro on 16 May, enabling local testing of patient samples for Ebola virus. [ 23 ]


Burials were organized by MSF and the  Red Cross of the Democratic Republic of the Congo  to minimize the risk of transmission. [ 24 ]  The  United Nations Radio   broadcast EVD awareness information, and posters and leaflets were prepared and distributed. [ 24 ]  UNICEF warned 143 churches across Mbandaka of the risks of prayer meetings. [ 25 ]


Health authorities including DRC's  Ministry of Public Health  used  recombinant   vesicular stomatitis virus – Zaire Ebola virus  ( rVSV-ZEBOV ) vaccine – a recently developed experimental  Ebola vaccine , produced by  Merck  – to try to suppress the outbreak. This  live-attenuated vaccine  expresses the surface  glycoprotein  of the Kikwit 1995 strain of  Zaire ebolavirus  in a recombinant  vesicular stomatitis virus   vector . [ 70 ]   rVSV-ZEBOV was trialed in  Guinea  and  Sierra Leone  during the  West African epidemic  of 2013–16, with 5837 people receiving the vaccine; the trial authors concluded that rVSV-ZEBOV provided "substantial protection" against EVD, [ 71 ]  but subsequent commentators have questioned the degree of protection obtained [ 72 ]  and the degree of long-term protection conferred is unknown. [ 73 ]  As the vaccine had not been approved by any regulatory authority, it was used in DRC under a  compassionate use  trial protocol. [ 6 ]


A  ring vaccination  strategy was used, which involves vaccinating only those most likely to be infected: direct contacts of infected individuals, and contacts of those contacts. [ 22 ] [ 74 ] [ 75 ] [ 76 ] [ 77 ]  Other groups targeted included health workers, laboratory personnel, surveillance workers and people involved with burials. [ 64 ] [ 78 ]  People who were vaccinated were followed up for 84 days to assess whether they were protected from infection and to monitor any adverse events. [ 6 ]  A total of 4,320 doses of the rVSV-ZEBOV vaccine were delivered to DRC's capital  Kinshasa  by WHO on 16 May, and a further 3,240 doses arrived three days later; [ 23 ]  with another 8,000 doses to be made available. [ 79 ]  The vaccine must be transported and stored at between −60 and −80 °C. [ 64 ]  A  cold chain  was established in Kinshasa by 18 May and has been extended to Mbandaka. WHO planned to concentrate on vaccinating three sets of contacts of confirmed EVD cases, two in Bikoro and one in Mbandaka. [ 24 ]


Vaccination started on 21 May among health workers in Mbandaka, [ 66 ]  with 7,560 vaccine doses ready for immediate use, according to WHO. [ 23 ] [ 64 ]  The DRC health minister  Oly Ilunga Kalenga  stated that vaccination of health workers and Ebola case contacts in the Wangata and  Bolenge  areas of Mbandaka would take five days, after which vaccination would start in Bikoro and Iboko. [ 66 ]  As of 24 May 2018 [update] , 154 people in Mbandaka had been vaccinated, and preparations were started for vaccinating in Bikoro and Iboko. [ 25 ]  Up to 1,000 people were expected to have been vaccinated by 26 May, according to WHO. [ 23 ]  It was the first time that vaccination had been attempted in the early stages of an Ebola outbreak. [ 6 ]


The rVSV-ZEBOV vaccine proved effective for the strain of the Ebola virus in this outbreak, having via ring vaccination protected some 3,481 individuals. [ 7 ]


Health officials considered trialing experimental treatments, including the antiviral agents  favipiravir  and  GS-5734 , and the antibody  ZMapp . All three agents were given to patients during the West African epidemic, but none has yet been proved to be effective. [ 80 ]  The DRC Ministry of Public Health also requested that the US trial mAb114 treatment during the outbreak. The  mAb114   monoclonal antibody  was developed by the  National Institutes of Health  and  Jean-Jacques Muyembe  at the National Institute for Biomedical Research, and is derived from an EVD survivor of the 1995  Kikwit  outbreak who still had circulating anti-Ebola antibodies eleven years later; it has been tested in  macaques  but not in humans. [ 53 ] [ 81 ] [ 82 ]


The  ZMapp  cocktail was assessed by the World Health Organization for emergency use under the  MEURI  ethical protocol. The panel agreed that "the benefits of ZMapp outweigh its risks" while noting that it presented logistical challenges, particularly that of requiring a  cold chain  for distribution and storage. [ 83 ]  Despite being at earlier stages of development, three other therapies,  mAb114 ,  remdesivir  and REGN3470-3471-3479, were also approved for emergency use under MEURI and the Ministry of Health in the DRC. [ 83 ] [ 84 ]


Post-Ebola virus syndrome  affects those who have survived EVD infection; the resulting signs and symptoms can include  muscle  pain, eye problems and  neurological  problems. [ 85 ]


The Democratic Republic of the Congo (formerly Zaire) has had several previous EVD outbreaks since 1976, [ 86 ] [ 87 ]  which are summarised in the Table below. All have been located in the west or north of the country. [ 79 ]  Three previous outbreaks (in 1976, 1977 and 2014) occurring in  former province of Équateur , of which the current  Équateur province  forms part. [ 2 ]


In 2014, the WHO considered that the DRC was lagging behind the rest of Africa in  health expenditures , at the relative rate of  Intl$ 32 per head. [ 88 ] [ 89 ]


For the  2017 Democratic Republic of the Congo Ebola virus outbreak , the DRC regulatory authorities approved the use of the experimental rVSV-ZEBOV vaccine, but logistical issues delayed its implementation until the outbreak was already under control. [ 6 ] [ 80 ] [ 90 ]


Shortly before the first cases of the 2018 Ebola outbreak, the country experienced a widespread  cholera  epidemic (June 2017 – spring 2018), which was the most serious in the country since 1994. [ 91 ] [ 92 ] [ 93 ]


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Ansuvimab , sold under the brand name  Ebanga , is a  monoclonal antibody  medication used for the treatment of  Zaire ebolavirus  (Ebolavirus) infection. [ 2 ] [ 3 ]


The most common symptoms include fever, tachycardia (fast heart rate), diarrhea, vomiting, hypotension (low blood pressure), tachypnea (fast breathing) and chills; however, these are also common symptoms of Ebolavirus infection. [ 2 ]


Ansuvimab was approved for medical use in the United States in December 2020. [ 2 ] [ 3 ] [ 4 ]  It is on the  World Health Organization's List of Essential Medicines . [ 5 ]


Ansuvimab is composed of a single  monoclonal antibody  (mAb) and was initially isolated from immortalized B-cells that were obtained from a survivor of the 1995 outbreak of  Ebola virus disease  in  Kikwit, Democratic Republic of the Congo . [ 6 ]  In work supported by the United States  National Institutes of Health  and the  Defense Advanced Projects Agency , the heavy and light chain sequences of ansuvimab mAb were cloned into  Chinese hamster ovary cell  lines and initial production runs were produced by Cook Phamica d.b.a. Catalent under contract with  Medimmune . [ 7 ] [ 8 ]


Ansuvimab is a  monoclonal antibody therapy  that is infused  intravenously  into people with  Ebola virus disease . Ansuvimab is a  neutralizing antibody , [ 6 ]  meaning it binds to a protein on the surface of  Ebola virus  that is required to infect cells. Specifically, ansuvimab neutralizes infection by binding to a region of the Ebola virus envelope glycoprotein that, in the absence of ansuvimab, would interact with virus's cell  receptor  protein,  Niemann-Pick C1 (NPC1) . [ 9 ] [ 10 ] [ 11 ]  This "competition" by ansuvimab prevents Ebola virus from binding to NPC1 and "neutralizes" the virus's ability to infect the targeted cell. [ 9 ]


Antibodies have  antigen-binding fragment (Fab)  regions and  constant fragment (Fc)  regions. The Neutralization of virus infection occurs when the Fab regions of antibodies binds to virus  antigen(s)  in a manner that blocks infection. Antibodies are also able to "kill" virus particles directly and/or kill infected cells using antibody-mediated "effector functions" such as opsonization,  complement-dependent cytotoxicity ,  antibody-dependent cell-mediated cytotoxicity  and antibody-dependent  phagocytosis . These effector functions are contained in the Fc region of antibodies, but is also dependent on binding of the Fab region to antigen. Effector functions also require the use of  complement  proteins in serum or  Fc-receptor  on cell membranes. Ansuvimab has been found to be capable of killing cells by antibody-dependent cell-mediated cytotoxicity. [ 6 ]


Ansuvimab is a  monoclonal antibody  that is being evaluated as a treatment for  Ebola virus disease . [ 12 ]  Its discovery was led by the laboratory of  Nancy Sullivan  at the United States  National Institutes of Health   Vaccine Research Center  and  J. J. Muyembe-Tamfum  from the  Institut National pour la Recherche Biomedicale  (INRB) in the  Democratic Republic of Congo , working in collaboration with the  Institute for Research in Biomedicine (IRB)  (Bellinzona, Switzerland) and the  United States Army Medical Research Institute of Infectious Diseases . [ 6 ] [ 13 ]  Ansuvimab was isolated from the blood of a survivor of the 1995 outbreak of  Ebola virus disease  in  Kikwit ,  Democratic Republic of Congo  roughly ten years later. [ 6 ]


In 2018, a  Phase 1 clinical trial  of ansuvimab was conducted by Martin Gaudinski within the  Vaccine Research Center   Clinical Trials Program  that is led by  Julie E. Ledgerwood . [ 8 ] [ 7 ] [ 14 ]  Ansuvimab is also being evaluated during the  2018 North Kivu Ebola outbreak . [ 15 ]


Ansuvimab has also shown success with lowering the mortality rate from ~70% to about 34%. In August 2019, Congolese health authorities, the World Health Organization, and the U.S. National Institutes of Health promoted the use of ansuvimab, alongside  atoltivimab/maftivimab/odesivimab , a similar  Regeneron -produced monoclonal antibody treatment, over other treatments yielding higher mortality rates, after ending clinical trials during the outbreak. [ 16 ] [ 17 ]


The U.S.  Food and Drug Administration  (FDA) approved ansuvimab based primarily on evidence from a clinical trial (Trial 1/ NCT NCT03719586) of 342 participants with  Zaire ebolavirus  infection. [ 4 ]  The trial enrolled newborn, pediatric and adult participants (including pregnant women) with  Zaire ebolavirus  infection. [ 4 ]  All participants received standard, supportive care for the disease. [ 4 ]  In addition to the standard care, participants were randomly assigned to receive either a one-time dose of ansuvimab or one of the three other types of experimental treatments (including one as the control group). [ 4 ]  The participants and the health care providers knew which treatment was being given. [ 4 ]  The trial was conducted at four sites in the Democratic Republic of Congo during an outbreak that began in August 2018. [ 4 ]


A 2016 paper describes the efforts of how ansuvimab was originally developed as part of research efforts led by Dr. Nancy Sullivan at the United States  National Institutes of Health   Vaccine Research Center  and Dr.  J. J. Muyembe-Tamfum  from the Institut National de Recherche Biomedicale (INRB) in the  Democratic Republic of Congo . [ 6 ] [ 13 ]  This collaborative effort also involved researchers from Institute of Biomedical Research and the  United States Army Medical Research Institute of Infectious Diseases . [ 6 ] [ 13 ]  A survivor from the 1995 outbreak of  Ebola virus disease  in  Kikwit ,  Democratic Republic of Congo  donated blood to the project that began roughly ten years after they had recovered. [ 6 ]   Memory B cells  isolated from the survivor's blood were  immortalized , cultured and screened for their ability to produce  monoclonal antibodies  that reacted with the glycoprotein of  Ebola virus . Ansuvimab was identified from one of these cultures and the  antibody  heavy and light chain gene sequences were sequenced from the cells. [ 6 ]  These sequences were then cloned into  recombinant DNA  plasmids and  purified antibody protein  for initial studies was produced in cells derived from  HEK 293 cells . [ 6 ]


In an experiment described in the 2016 paper,  rhesus macaques  were infected with Ebola virus and treated with a combination of ansuvimab and another antibody isolated from the same subject, mAb100. Three doses of the combination were given once a day starting 1 day after the animals were infected. The control animal died and the treated animals all survived. [ 6 ]


In a second experiment described in the 2016 paper,  rhesus macaques  were infected with Ebola virus and only treated with ansuvimab. Three doses of ansuvimab were given once a day starting 1 day or 5 days after the animals were infected. The control animals died and the treated animals all survived. [ 6 ]  Unpublished data referred to in a publication of the 2018 Phase I clinical trial results of ansuvimab, reported that a single infusion of ansuvimab provided full protection of rhesus macaques and was the basis of the dosing used for human studies. [ 8 ] [ 7 ]


Ansuvimab was developed by the  Vaccine Research Center  with support of the United States  National Institutes of Health  and the  Defense Advanced Projects Agency . The heavy and light chain sequences of ansuvimab mAb were cloned into  CHO cell lines  to enable large-scale production of antibody product for use in humans. [ 7 ] [ 8 ]


In early 2018, [ 12 ]  a  Phase 1  clinical trial of ansuvimab's safety, tolerability and  pharmacokinetics  was conducted by Dr. Martin Gaudinski within the  Vaccine Research Center   Clinical Trials Program  that is led by  Dr. Julie E. Ledgerwood . [ 8 ] [ 7 ] [ 14 ]  The study was performed in the United States at the  NIH Clinical Center  and tested single dose infusions of ansuvimab infused over 30 minutes. The study showed that ansuvimab was safe, had minimal side effects and had a  half-life  of 24 days. [ 8 ] [ 7 ]


A license for ansuvimab was obtained by  Ridgeback Biotherapeutics  in 2018, from the  National Institutes of Health - National Institute of Allergy and Infectious Diseases . [ 18 ]  Ansuvimab was given  orphan drug  status in May 2019 and March 2020. [ 19 ] [ 20 ] [ 21 ]


During the  2018 Équateur province Ebola outbreak , ansuvimab was requested by the  Democratic Republic of the Congo  (DRC) Ministry of Public Health. Ansuvimab was approved for  compassionate use  by the  World Health Organization   MEURI  ethical protocol and at DRC ethics board. Ansuvimab was sent along with other therapeutic agents to the outbreak sites. [ 22 ] [ 23 ] [ 14 ]  However, the outbreak came to a conclusion before any therapeutic agents were given to people. [ 14 ]


Approximately one month following the conclusion of the Équateur province outbreak, a distinct outbreak was noted in  Kivu  in the DRC ( 2018–20 Kivu Ebola outbreak ). Once again, ansuvimab received approval for compassionate use by WHO MEURI and DRC ethic boards and has been given to many people under these protocols. [ 14 ]  In November 2018, the Pamoja Tulinde Maisha (PALM [together save lives]) open-label randomized clinical control trial was begun at multiple treatment units testing ansuvimab,  atoltivimab/maftivimab/odesivimab  (REGN-EB3) and  remdesivir  to  ZMapp . Despite the difficulty of running a clinical trial in a conflict zone, investigators enrolled 681 participants towards their goal of 725. An interim analysis by the Data Safety and Monitoring Board (DSMB) of the first 499 participants found that ansuvimab and REGN-EB3 were superior to the comparator  ZMapp . Overall mortality of participants in the ZMapp and remdesivir groups were 49% and 53% compared to 34% and 29% for ansuvimab and REGN-EB3. When looking at participants who arrived early after disease symptoms appeared, survival was 89% for ansuvimab and 94% for REGN-EB3. While the study was not  powered  to determine whether there is any difference between REGN-EB3 and ansuvimab, the survival difference between those two therapies and ZMapp was significant. This led to the DSMB halting the study and PALM investigators dropping the remdesivir and ZMapp arms from the clinical trial. All people in the outbreak who elect to participate in the trial will now be given either ansuvimab or REGN-EB3. [ 24 ] [ 25 ] [ 16 ] [ 15 ]


In October 2020, the US  Food and Drug Administration  (FDA) approved  atoltivimab/maftivimab/odesivimab  (Inmazeb, formerly REGN-EB3) with an  indication  for the treatment of infection caused by  Zaire ebolavirus . [ 26 ]


Atoltivimab  is a  Zaire ebolavirus  glycoprotein-directed human monoclonal antibody that is part of the  fixed-dose combination   atoltivimab/maftivimab/odesivimab  that is used for the treatment of  Zaire ebolavirus  ( Ebola  virus). [ 1 ] [ 2 ] [ 3 ]


This  antiinfective   drug  article is a  stub . You can help Wikipedia by  expanding it .


Atoltivimab/maftivimab/odesivimab , sold under the brand name  Inmazeb , is a  fixed-dose combination  of three monoclonal antibodies for the treatment of  Zaire ebolavirus  ( Ebola  virus). [ 2 ]  It contains  atoltivimab ,  maftivimab , and  odesivimab-ebgn  and was developed by  Regeneron Pharmaceuticals . [ 2 ]


The most common side effects include fever, chills,  tachycardia  (fast heart rate),  tachypnea  (fast breathing), and vomiting; however, these are also common symptoms of Ebola virus infection. [ 2 ] [ 3 ]


Atoltivimab/maftivimab/odesivimab is the first FDA-approved treatment for  Zaire ebolavirus . [ 2 ]  Atoltivimab/maftivimab/odesivimab was approved for medical use in the United States in October 2020. [ 2 ] [ 4 ] [ 5 ] [ 3 ] [ 6 ]  The U.S.  Food and Drug Administration  (FDA) considers it to be a  first-in-class medication . [ 7 ]  It is on the  World Health Organization's List of Essential Medicines . [ 8 ]


Atoltivimab/maftivimab/odesivimab is  indicated  for the treatment of infection caused by  Zaire ebolavirus . [ 2 ]


People who receive atoltivimab/maftivimab/odesivimab should avoid the concurrent administration of a live vaccine due to the treatment's potential to inhibit replication of a live vaccine virus indicated for prevention of Ebola virus infection and possibly reduce the vaccine's efficacy. [ 2 ]


Atoltivimab/maftivimab/odesivimab is a combination of  Zaire ebolavirus  glycoprotein-directed human monoclonal antibodies. [ 2 ]  The three antibodies target the  glycoprotein  that is on the surface of the Ebola virus. [ 2 ]  This glycoprotein normally attaches to the cell via a receptor and fuses the viral and host cell membranes allowing the virus to enter the cell. [ 2 ]  The antibodies can bind to it simultaneously at three different locations and block attachment and entry of the virus. [ 2 ]


This combination drug targets the Zaire species of Ebola virus. The Sudan and  Bundibugyo  strains have also caused outbreaks, and it is unlikely that it would be effective against these strains. [ 9 ]


The 2014 Ebola outbreak killed more than 11,300 people. Regeneron used its VelociGene, VelocImmune and VelociMab antibody discovery and production technologies and coordinated with the U.S. government's  Biomedical Advanced Research and Development Authority  (BARDA). [ 10 ]   The therapy was developed in six months and a Phase 1 trial in healthy humans was completed in 2015. [ 10 ]


During the  2018 Équateur province Ebola outbreak , a similar monoclonal antibody treatment,  mAb114 , was requested by the Democratic Republic of Congo (DRC) Ministry of Public Health. mAb114 was approved for  compassionate use  by the  World Health Organization   MEURI  ethical protocol and at DRC ethics board. mAb114 was sent along with other therapeutic agents to the outbreak sites. [ 11 ] [ 12 ] [ 13 ]  However, the outbreak came to a conclusion before any therapeutic agents were given to patients. [ 13 ]


Approximately one month following the conclusion of the Équateur province outbreak, a distinct outbreak was noted in  Kivu  in the DRC ( 2018–20 Kivu Ebola outbreak ). Once again, mAb114 received approval for compassionate use by WHO MEURI and DRC ethic boards and has been given to many patients under these protocols. [ 13 ]  In November 2018, the Pamoja Tulinde Maisha (PALM [together save lives]) open-label randomized clinical control trial was begun at multiple treatment units testing mAb114, REGN-EB3 and  remdesivir  to  ZMapp . Despite the difficulty of running a clinical trial in a conflict zone, investigators have enrolled 681 patients towards their goal of 725. [ citation needed ]


This is the second largest outbreak with (as of January 2020) over 3,400 confirmed or probable cases, including more than 2,200 who have died. [ 14 ] [ 15 ]


An interim analysis by the Data Safety and Monitoring Board (DSMB) of the first 499 patient found that mAb114 and REGN-EB3 were superior to the comparator  ZMapp . Overall mortality of patients in the ZMapp and Remdesivir groups were 49% and 53% compared to 34% and 29% for mAb114 and REGN-EB3. When looking at patients who arrived early after disease symptoms appeared, survival was 89% for mAB114 and 94% for REGN-EB3.  While the study was not  powered  to determine whether there is any difference between REGN-EB3 and mAb114, the survival difference between those two therapies and ZMapp was significant. This led to the DSMB halting the study and PALM investigators dropping the remdesivir and ZMapp arms from the clinical trial. All patients in the outbreak who elect to participate in the trial will now be given either mAb114 or REGN-EB3. [ 16 ] [ 17 ] [ 18 ] [ 19 ]


In August 2019, Congolese health officials announced it was more effective compared to two other treatments being used at the time. [ 20 ] [ 18 ] [ 21 ]


Among patients treated with it, 34% died; the mortality rate improved if the drug was administered soon after infection, in a timely diagnosis – critical for those infected with diseases like Ebola that can cause  sepsis  and, eventually,  multiple organ dysfunction syndrome , more quickly than other diseases. [ 22 ]   The survival rate if the drug was administered shortly after the infection was 89%. [ 14 ]


Atoltivimab/maftivimab/odesivimab was evaluated in 382 adult and pediatric participants with confirmed  Zaire ebolavirus  infection in one clinical trial (the PALM trial) and as part of an expanded access program conducted in the Democratic Republic of the Congo (DRC) during an Ebola virus outbreak in 2018/2019. [ 2 ] [ 3 ]  In the PALM trial, the safety and efficacy of atoltivimab/maftivimab/odesivimab was evaluated in a multi-center, open-label, randomized controlled trial, in which 154 participants received atoltivimab/maftivimab/odesivimab (50 mg of each monoclonal antibody) intravenously as a single infusion, and 168 participants received an investigational control. [ 2 ]  The trial enrolled pediatric and adult participants (including pregnant women) with Zaire ebolavirus infection. [ 3 ]  All participants received standard, supportive care for the disease. [ 3 ]  The participants and the health care providers knew which treatment was being given. [ 3 ]  The primary efficacy endpoint was 28-day mortality. [ 2 ]  The primary analysis population was all participants who were randomized and concurrently eligible to receive either atoltivimab/maftivimab/odesivimab or the investigational control during the same time period of the trial. [ 2 ]  Of the 154 participants who received atoltivimab/maftivimab/odesivimab, 33.8% died after 28 days, compared to 51% of the 153 participants who received a control. [ 2 ]  In the expanded access program, an additional 228 participants received atoltivimab/maftivimab/odesivimab. [ 2 ]


The FDA granted the application of atoltivimab/maftivimab/odesivimab-ebgn  orphan drug  and  breakthrough therapy  designations. [ 2 ]  The FDA granted the approval of Inmazeb to Regeneron Pharmaceuticals with an  indication  for the treatment of infection caused by  Zaire ebolavirus  in October 2020. [ 2 ] [ 6 ]


The drug has also received orphan drug designation from the  European Medicines Agency . [ 23 ]


This is a  bibliography of the  Ebola virus disease , also known as  Ebola hemorrhagic fever , a viral  hemorrhagic fever  of humans and other primates caused by  ebolaviruses . [ 1 ]


It includes non-fiction works relating to the background and history of the disease, general works, memoirs of those involved in outbreaks such as health workers, works about the effects on particular groups of individuals, and a link to the World Health Organization list of publications about Ebola.


Full list here .


The  Liberia n government is conducting a  birth registration  campaign  to record more than 70,000 children whose births were not listed during the  Ebola crisis  of 2014 and 2015. [ 1 ] [ 2 ] [ 3 ]  Previously Liberia had the second lowest rate of birth registration at 4 percent. But a Universal Birth Registration Plan was introduced, and by 2013, birth registration drives had increased the rates in Liberia to 25 percent. [ 1 ]


During the Ebola outbreak in 2014 and 2015, Liberia birth registrations dropped sharply. In 2014 many health facilities closed or had reduced services in response to the Ebola crisis, and there was a 39 per cent decrease in births registered over the previous year. In 2013, before the beginning of the Ebola epidemic, the births of 79,000 children were registered, while in 2014 the number of registrations dropped to 48,000. [ 1 ]  And only 700 children in Liberia had their births registered between January and May 2015. [ 1 ]   UNICEF  is supporting a drive to implement registration systems throughout the country, and will assist with training and outreach for a nationwide campaign to register the children missed in 2014 and 2015. [ 3 ]


Historically, Liberia had a low level of birth registrations. In 2007, birth registration rates were estimated at 4 or 5 percent. [ 1 ] [ 4 ]  A field survey by the Ministry of Health and Social Welfare in 2008 indicated that was not a properly working birth registration system in Liberia. [ 5 ]  The government in Liberia identified the development of an improved birth registration system as a national priority in the  Liberian Poverty Reduction Strategy. [ 6 ]  And by 2013, birth registration drives had increased the rates in Liberia to 25 percent. [ 1 ]


Brincidofovir , sold under the brand name  Tembexa , is an  antiviral drug  used to treat  smallpox . Brincidofovir is a  prodrug  of  cidofovir . [ 4 ]  Conjugated to a  lipid , the compound is designed to release cidofovir  intracellularly , allowing for higher intracellular and lower plasma concentrations of cidofovir, effectively increasing its activity against  dsDNA viruses , as well as oral  bioavailability . [ 5 ]


The most common side effects include diarrhea, nausea, vomiting, and abdominal pain. [ 3 ]  It carries an FDA-mandated  black box warning  of an increased risk of death with extended use. [ 6 ] [ 7 ]
Brincidofovir was approved for medical use in the United States in June 2021.


Brincidofovir is  indicated  for the treatment of human smallpox disease caused by the variola virus. [ 3 ] [ 8 ]


Brincidofovir is a  prodrug  that is composed of cidofovir  conjugated  with a  lipid  molecule. The lipid aspect of the molecule takes on the action of endogenous lysophosphatidyl choline, which then is able to enter cells in the body which are infected with smallpox. [ 9 ]  Once the infected cell takes in the drug, the drug cleaves to generate cidofovir. Cidofovir is then consequently phosphorylated to yield cidofovir diphosphate, which is the active drug. Cidofovir diphosphate inhibits the variola virus'  DNA polymerase -mediated DNA synthesis. The drug acts as an acyclic nucleotide and incorporates itself into the viral DNA chain, which then stops viral DNA synthesis. [ 10 ]


The oral bioavailability of Brincidofovir is 13.4% as a tablet and 16.8% in a suspension. [ 9 ]  The metabolism of the drug is as such: once the drug enters the target infected cell, Brincidofovir's phosphodiester bond is then hydrolyzed to generate cidofovir which is then phosphorylated to the active cidofovir diphosphate. The volume of distribution of the drug is 1230 L. [ 9 ]


Because smallpox is eradicated, the effectiveness of brincidofovir was studied in animals infected with viruses that are closely related to the variola virus. [ 3 ]  Effectiveness was determined by measuring animals' survival at the end of the studies. [ 3 ]


Safety information to support approval of brincidofovir was derived from clinical trials of the drug for a non-smallpox indication, primarily from patients who received hematopoietic stem cell transplants. [ 3 ]


The U.S.  Food and Drug Administration  (FDA) granted the application for brincidofovir  priority review ,  fast track , and  orphan drug  designations. [ 3 ]  The FDA approved brincidofovir under the agency's Animal Rule, which allows findings from adequate and well-controlled animal efficacy studies to serve as the basis of an approval when it is not feasible or ethical to conduct efficacy trials in humans. [ 3 ]


Brincidofovir (CMX001) was the subject of widespread  social media campaigning  in 2014, which was then picked up by national news sources about a boy with an  adenovirus infection  following a  bone marrow transplant . [ 11 ]   The family requested  legal access to the still-unapproved drug outside of any clinical trial , and Chimerix initially denied the request.  After a short and intense media campaign, Chimerix got permission from the FDA to start a limited  open-label trial  which allowed the boy to receive the drug. [ 11 ]   This media event sparked a debate on the ethics of using social media, the allocation of limited resources of a small company, and the emphasis on the individual over the group. The new use of any drug has the potential to interfere with the process to get the drug approved and widely marketed, through means such as consuming limited staff time that may be needed elsewhere – staff time that has the potential to save thousands of lives in the long-term, rather than one life now – overwhelming manufacturing capabilities, or by causing adverse effects or even death. [ 11 ]   These  adverse events  are more likely during these programs, because the people seeking access are usually much sicker than most, and problems experienced by these people can result in an unfavorable and inaccurate perception of the drug's safety profile. [ 11 ]   In this case, the boy recovered from the infection in 2014, and died in 2016 from complications of cancer. [ 12 ]


Brincidofovir is one of several experimental drugs administered to a small number of patients to treat Ebola virus disease during the 2014 outbreak. The WHO published a report on the ethics of using unregistered interventions to treat Ebola, where they concluded that "In the particular context of the current Ebola outbreak in West Africa, it is ethically acceptable to offer unproven interventions that have shown promising results in the laboratory and in animal models but have not yet been evaluated for safety and efficacy in humans as potential treatment or prevention." [ 13 ]


Brincidofovir is under investigation for the treatment of  cytomegalovirus ,  adenovirus ,  poxvirus , and  ebolavirus  infections. [ 14 ]  It has been used off-label for the treatment of  monkeypox . [ 15 ]


As of 2014 [update] , brincidofovir is in  Phase III clinical trials  for use in humans against cytomegalovirus and adenovirus. Preliminary safety data from a database of 1000 patients supported progression into later phase trials, [ 16 ]  Chimerix announced in December 2015 that the Phase III trials for use of the drug in preventing  cytomegalovirus  infection in  stem cell transplant  patients had failed, and in February 2016 shut down two other late-stage trials for use of the drug in preventing infection after  kidney transplants . Brincidofovir is not yet FDA approved for adenovirus or cytomegalovirus due to lack of efficacy in clinical trials. [ 17 ]  In a trial of brincidofovir for patients with CMV brincidofovir was associated with a 15.5% week 24 all-cause mortality compared with 10.1% among placebo recipients. Additionally brincidofovir was associated with increased serious adverse events (57.1% versus 37.6%) compared with placebo. [ 17 ]  Brincidofovir was initially offered via an FDA expanded access trial; however as of 9 May 2019, Chimerix discontinued clinical trials of brincidofovir for the treatment of adenovirus and discontinued the expanded access program in 2019. [ 18 ]


After initial studies by the Centers for Disease Control and Prevention (CDC, Atlanta, Georgia, US) in cell culture models, [ 19 ]  on 6 October 2014, Chimerix received an  FDA  authorization for emergency investigational new drug applications of brincidofovir for the treatment of Ebola virus disease. Brincidofovir was administered to the first patient diagnosed in the  Ebola virus disease outbreak in the US in 2014 . [ 20 ] [ 21 ]  The patient was given the drug starting six days after hospital admission when he was already critically ill; he died four days later. [ 22 ] [ 23 ]  Brincidofovir was also given to Ebola patient Ashoka Mukpo at the Nebraska Medical Center, who had developed the disease and then was pronounced Ebola-free and released from the center on 22 October 2014. [ 24 ]


In October 2014, Chimerix reported it had been given approval by the FDA to start Phase 2 trials in patients infected with ebolaviruses for brincidofovir's safety, tolerability, and efficacy. [ 25 ]  Organised by a team of scientists at the University of Oxford, including  Peter Horby , Jake Dunning, Laura Merson and  Trudie Lang , [ 26 ]  a trial commenced during January 2015 in Liberia, [ 27 ]  but was subsequently discontinued. Because of a lack of suitable subjects in Liberia,  Oxford University  and  Médecins Sans Frontières  planned to extend the trial to  Sierra Leone , where there were still Ebola cases; but on 30 January 2015, the manufacturer decided to withdraw support for the trial and end discussion of future trials. [ 28 ] [ 29 ]


In animal trials brincidofovir has shown activity against cytomegalovirus,  adenoviruses ,  BK virus ,  poxviruses , and  herpes simplex viruses . [ 4 ] [ 30 ]  Brincidofovir appears to have potential for the treatment of  Ebola virus disease , which is somewhat paradoxical, as ebolaviruses are  RNA viruses  and thus do not contain DNA as the above-mentioned viruses. [ 19 ] [ 31 ]


cAd3-ZEBOV  (also known as  the NIAID/GSK Ebola vaccine  or  cAd3-EBO Z ) was an experimental  vaccine  for two  ebolaviruses ,  Ebola virus  and  Sudan virus , developed by scientists at  GlaxoSmithKline  (GSK) and tested by  National Institute of Allergy and Infectious Disease  (NIAID). [ 1 ]  This vaccine is derived from a  chimpanzee   adenovirus , Chimp Adenovirus type 3 (ChAd3),  genetically engineered  to express  glycoproteins  from the Zaire and Sudan species of  ebolavirus  to provoke an immune response against them. Simultaneous  phase 1  trials of this vaccine commenced in September 2014, being administered to volunteers in Oxford and Bethesda. [ 2 ]  During October the vaccine is being administered to a further group of volunteers in  Mali . If this phase is completed successfully, the vaccine will be fast tracked for use in the  Ebola virus epidemic in West Africa . In preparation for this, GSK is preparing a stockpile of 10,000 doses. [ 3 ] [ 4 ]


Following ten Americans who received the vaccine in a trial,  Ruth Atkins  (born 1966) [ 5 ]  of Oxfordshire, a former nurse with the British  National Health Service , was the first British volunteer to receive the experimental  vaccine  (on September 17, 2014) in a vaccine trial run by  Oxford University  researchers and funded by the  Wellcome Trust  and the UK government. This variant was only designed to protect against  Ebola virus  and not  Sudan virus . [ 6 ]


Ebola ‘76  ( Arabic :  إيبولا 76 ) is a 2012 novel written by Sudanese author and medical doctor  Amir Taj al-Sir . [ 2 ]  Originally written in Arabic, the novel recounts the  1976 Ebola outbreak  in Sudan.


On a hot, humid August day in 1976,  The Democratic Republic of Congo  is the setting of the first major  Ebola  outbreak. Unfortunately, the outbreak is difficult to contain and control due to the squalid living conditions as a result of deep poverty, and the population's ignorance and apathy regarding the virus. These 2 factors help the Ebola strain to fester and spread to an epidemic affecting the city  Kinshasa  heavily. As luck would have it, an ordinary Sudanese factory worker by the name Lewis, who happened to stop through Kinshasa on his way back to his home, contracted the virus from an escort during an adulterous romp and consequently brought it back to his home in  Nzara  to subsequently spread like wildfire. The novel goes on and shows Ebola's path of destruction in Nzara through Lewis' social connections and its devastating effect on the town as a whole.


Critical reception for  Ebola '76  was mostly positive and the novel also received positive reader responses. [ 4 ] [ 5 ] [ 6 ]   The Guardian  was mixed in their review, stating that "Like a medieval danse macabre, Ebola leads a parade of wretches to the grave, but Tag Elsir’s apparent disdain for his characters robs his narrative of empathy and leaves the reader indifferent to the fate of Lewis, the blind guitarist Ruwadi, the washed‑up magician Jamadi and the rest." [ 7 ]   Asymptote  was more favorable, writing that "Though it is a quick fictional account,  Ebola ’76  is an educational read about the emergence of the Ebola virus and how it could have possibly spread from the DRC to South Sudan." [ 8 ]  Reviewing for the  American Historical Association , Shatha Almutawa felt that "Despite the gravity of the subject of the novel, the language is witty and the mood light-seeing the world from the perspective of the virus, after all, is very different from seeing it from the perspective of grief-stricken men who lost their lovers." [ 9 ]


Ebola virus disease in the United Kingdom and Ireland  has occurred rarely in four cases to date, namely three health workers returning from treating victims of the  Ebola virus epidemic in West Africa  in 2014 and 2015, and a single case in 1976, when a laboratory technician contracted the disease in a  needlestick injury  while handling samples from Africa. All cases recovered.
As of 2023, no domestic transmission of Ebola has occurred in the United Kingdom or Ireland.


On 5 November 1976, Geoffrey Platt, a laboratory technician at the former Microbiological Research Establishment in  Porton Down ,  Wiltshire , contracted Ebola in an accidental  needlestick injury  from a contaminated needle while handling samples from Africa. [ 1 ]  He was treated with  human interferon  and  convalescent serum . The course of his disease was mild and he fully recovered. [ 2 ] [ 3 ]


The  high-level isolation unit  at the  Royal Free Hospital , in the  Hampstead  area of  London , received its first case on 24 August 2014. William Pooley, a British nurse who contracted the disease while working in  Sierra Leone  as part of the relief effort for the  Ebola virus epidemic in West Africa , was  medically evacuated  by the  Royal Air Force  on a specially-equipped  C-17  aircraft. [ 4 ]
He was released from hospital on 3 September 2014. [ 5 ]   Pooley delivered the UK's  Channel 4  television program  Alternative Christmas message  in 2014. [ 6 ]  He was reported to be planning to return to Sierra Leone on 19 October 2014. [ 7 ]  He also donated blood to support developing a cure for the disease. [ 7 ]


On 29 December 2014,  Pauline Cafferkey , a Scottish aid worker who had just returned from an Ebola treatment centre in  Kerry Town  in Sierra Leone to  Glasgow   via  Casablanca Airport  and  London Heathrow Airport , was diagnosed with Ebola virus disease at Glasgow's  Gartnavel General Hospital . [ 8 ] [ 9 ] [ 10 ]  it was thought she contracted the virus as a result of wearing a visor instead of goggles. [ 11 ]  Criticism was levelled at screening protocols at UK points of entry, which mainly consisted of taking a person's temperature and asking a series of questions. [ 12 ]


After initial treatment in Glasgow, she was transferred to the specialist  high-level isolation unit  at the  Royal Free Hospital  in  London  for longer-term treatment. [ 9 ] [ 13 ]   Contact tracing  was carried out on the other passengers who had traveled on the flight from London to Glasgow with her. [ 13 ]  In January 2015, she experienced a period of  critical illness , [ 14 ]  and underwent intensive medical treatment. [ 15 ]  In January 2015 she was declared to be free of infection, and released from hospital. [ 16 ]


In October 2015, Cafferkey was diagnosed with late complications caused by the Ebola virus hitherto considered unusual, and readmitted to the  Royal Free Hospital . The virus had remained in her  cerebrospinal fluid  and was feared to be in her central nervous system. [ 17 ]  Her doctors stated that she had been  critically ill  due to neurological complications from meningitis, and that she had been treated using a highly experimental  anti-viral  agent. [ 18 ] [ 19 ] [ 20 ]  On 12 November the Royal Free Hospital said that Cafferkey had made a full recovery and was no longer infectious. [ 21 ]


In February 2016, Cafferkey was readmitted to the Royal Free Hospital due to complications from her infection, [ 22 ]  but later that month declared not to be infectious and discharged. [ 23 ]  In October 2016, she was again admitted to hospital, monitored by the infectious diseases unit at Glasgow's  Queen Elizabeth University Hospital , [ 24 ]  but tests for the Ebola virus were negative. [ 25 ]


In 2016, proceedings were initiated against Cafferkey by the  Nursing and Midwifery Council  alleging that she had allowed an incorrect temperature to be recorded during the screening process upon returning to the UK from Sierra Leone in 2014. Following a hearing in September 2016, the charges against her were dismissed after the disciplinary panel was told that she had been impaired by illness at the time. [ 26 ]


On 11 March 2015, a UK military health worker contracted the disease in Sierra Leone while volunteering as a nurse. After testing positive for Ebola she was flown home for treatment at Royal Free Hospital in London. [ 27 ]  On 27 March 2015 Corporal Anna Cross, the UK military worker who tested positive for Ebola, was the first person in the world to be treated with the experimental Ebola drug MIL 77 and was released from hospital after making a full recovery. The doctors treating her at London's Royal Free Hospital confirmed it is too soon to speculate if the drug helped in her recovery. [ 28 ]


Healthcare workers who in January 2015 had sustained  needlestick injuries  while caring for Ebola patients abroad were put under medical observation, but not found to have contracted the Ebola virus. [ 29 ] [ 30 ] [ 31 ]
On 16 March 2015, another UK worker had been sent back to the United Kingdom from Sierra Leone due to fear of having contracted the virus. [ 32 ]  but did not test positive.


On 17 November  Colchester Hospital  deep cleaned after a suspected case of the  2022 Uganda Ebola outbreak , [ 33 ]  which as of December was not confirmed as an Ebola case.


In November 2014,  Public Health England  established the returning workers scheme, mandating organisations and businesses to register and provide travel details of all staff returning from Ebola affected areas before they travel back to the UK. [ 34 ]


In October 2022, the UK Health Security Agency issued a health alert asking providers to considering Ebola in the  differential diagnosis  of any patient with relevant symptoms returning from areas affected by the  outbreak of Sudan ebolavirus in Uganda . [ 35 ]


The  Ebola River  ( / i ˌ b oʊ l ə /  or  / ə ˈ b oʊ l ə / ), [ 1 ] [ 2 ]  also commonly known by its Ngbandi name  Legbala , [ 3 ]  is the  headstream  of the  Mongala River , a tributary of the  Congo River , in northern  Democratic Republic of the Congo . [ 4 ]   It is roughly 250 kilometers (160 mi) in length. [ citation needed ]


The name  Ebola  is a French corruption of  Legbala , its name in  Ngbandi  which means 'white water'. [ 5 ]  During the  Belgian administration  these names were interchangeable along with the French names  Eau Blanche [ 3 ]  and rarely  L'Ébola . [ 5 ]


In 1976,  Ebola virus  was first identified in  Yambuku , 111 kilometers (69 mi) from the Ebola River, but the virologist  Karl Johnson  decided to name it after the river so that the town would not be associated with the disease's stigma. [ 5 ]  Thus, the river is eponymous to the terms  Ebola virus ,  Ebolavirus , and  Ebola virus disease  (usually referred to as simply "Ebola"). [ 6 ]


Media related to  Ebola River  at Wikimedia Commons


This article related to a river in the  Democratic Republic of the Congo  is a  stub . You can help Wikipedia by  expanding it .


Ebola vaccines  are  vaccines  either approved or in development to prevent  Ebola . As of 2022, there are only vaccines against the  Zaire ebolavirus . The first vaccine to be approved in the United States was  rVSV-ZEBOV  in December 2019. [ 9 ] [ 10 ]  It had been used extensively in the  Kivu Ebola epidemic  under a  compassionate use  protocol. [ 11 ]  During the early 21st century, several vaccine candidates displayed efficacy to protect nonhuman primates (usually  macaques ) against lethal infection. [ 12 ] [ 13 ] [ 14 ]


Vaccines include  replication -deficient  adenovirus   vectors , replication-competent  vesicular stomatitis  (VSV) and  human parainfluenza  (HPIV-3) vectors, and virus-like  nanoparticle  preparations. Conventional trials to study efficacy by exposure of humans to the pathogen after immunization are not ethical in this case. For such situations, the US  Food and Drug Administration  (FDA) has established the " animal efficacy rule " allowing licensure to be approved on the basis of  animal model  studies that replicate human disease, combined with evidence of safety and a potentially potent  immune response  (antibodies in the blood) from humans given the vaccine.  Clinical trials  involve the administration of the vaccine to healthy human subjects to evaluate the immune response, identify any side effects and determine the appropriate dosage. [ 15 ]


VSV-EBOV or  rVSV-ZEBOV , sold under the brand name Ervebo, is a vaccine based on the  vesicular stomatitis  virus which was genetically modified to express a surface  glycoprotein  of  Zaire Ebola virus . [ 16 ] [ 17 ]  In November 2019, the European Commission granted a conditional marketing authorization. [ 18 ]  The WHO prequalification came fewer than 48 hours later, making it the fastest vaccine prequalification process ever conducted by WHO. [ 19 ]  It was approved for medical use in the European Union in November 2019. [ 3 ]  It was approved for medical use in the United States in December 2019. [ 9 ] [ 2 ]


The most common side effects include pain, swelling and redness at the injection site, headache, fever, muscle pain, tiredness and joint pain. [ 3 ]  In general, these reactions occur within seven days after vaccination, are mild to moderate in intensity and resolved in less than a week. [ 3 ]


It was developed by the  Public Health Agency of Canada , with development subsequently taken over by  Merck Inc . [ 20 ]  In October 2014, the  Wellcome Trust , who was also one of the biggest UK founders, [ 21 ]  announced the start of multiple trials in healthy volunteers in Europe, Gabon, Kenya, and the US. [ 22 ]  The vaccine was proven safe at multiple sites in North America, Europe, and Africa, but several volunteers at one trial site in Geneva, Switzerland, developed vaccine-related arthritis after about two weeks, and about 20–30% of volunteers at reporting sites developed low-grade post-vaccine fever, which resolved within a day or two. Other common side-effects were pain at the site of injection, myalgia, and fatigue. [ 23 ]  The trial was temporarily halted in December 2014 due to possible adverse effects, but subsequently resumed. [ 24 ]  As of April 2015 [update] , a Phase III trial with a single dose of VSV-EBOV began in Liberia after a successful Phase II study in the West African country. [ 25 ]  On 31 July 2015, preliminary results of a Phase III trial in Guinea indicated that the vaccine appeared to be "highly efficacious and safe." [ 26 ]  The trial used a  ring vaccination  protocol that first vaccinated all the closest contacts of new cases of Ebola infection either immediately or after 21 days. Because of the demonstrated efficacy of immediate vaccination, all recipients will now be immunized immediately. [ 27 ] [ 28 ]  Ring vaccination is the method used in the program to eradicate  smallpox  in the 1970s. The trial will continue to assess whether the vaccine is effective in creating  herd immunity  to Ebola virus infection. [ 29 ]  In December 2016, a study found the VSV-EBOV vaccine to be 95–100% effective against the Ebola virus, making it the first proven vaccine against the disease. [ 30 ] [ 31 ] [ 32 ]


The approval was supported by a study conducted in Guinea during the  2014–2016 outbreak  in individuals 18 years of age and older. [ 9 ]  The study was a randomized cluster (ring) vaccination study in which 3,537 contacts, and contacts of contacts, of individuals with laboratory-confirmed Ebola virus disease (EVD) received either "immediate" or 21-day "delayed" vaccination. [ 9 ]  This design was intended to capture a social network of individuals and locations that might include dwellings or workplaces where a patient spent time while symptomatic, or the households of individuals who had contact with the patient during that person's illness or death. [ 9 ]  In a comparison of cases of EVD among 2,108 individuals in the "immediate" vaccination arm and 1,429 individuals in the "delayed" vaccination arm, Ervebo was determined to be 100% effective in preventing Ebola cases with symptom onset greater than ten days after vaccination. [ 9 ]  No cases of EVD with symptom onset greater than ten days after vaccination were observed in the "immediate" cluster group, compared with ten cases of EVD in the 21-day "delayed" cluster group. [ 9 ]


In additional studies, antibody responses were assessed in 477 individuals in Liberia, some 500 individuals in Sierra Leone, and about 900 individuals in Canada, Spain, and the US. [ 9 ]  The antibody responses among those in the study conducted in Canada, Spain and the US were similar to those among individuals in the studies conducted in Liberia and Sierra Leone. [ 9 ]


The safety was assessed in approximately 15,000 individuals in Africa, Europe, and North America. [ 9 ]  The most commonly reported side effects were pain, swelling and redness at the injection site, as well as headache, fever, joint and muscle aches and fatigue. [ 9 ]


In December 2016, a study found the VSV-EBOV vaccine to be 70–100% effective against the Ebola virus, making it the first proven vaccine against the disease. [ 30 ] [ 31 ] [ 32 ]  However, the design of this study and the high efficacy of the vaccine were questioned. [ 33 ]  In November 2019, the European Commission granted a conditional marketing authorization to Ervebo (rVSV∆G-ZEBOV-GP, live) [ 18 ] [ 34 ] [ 4 ]  and the WHO prequalified an Ebola vaccine for the first time. [ 19 ]


In July 2023, the FDA expanded the indication for Ervebo to cover people aged 12 years of age and older. [ 35 ] [ 36 ]


Merck ’s Ebola vaccine demonstrated significant effectiveness during the 2018-2020 outbreak in the  Democratic Republic of the Congo , providing 84% protection to individuals vaccinated at least 10 days prior to exposure. [ 37 ]  This finding, detailed in a study published in  The Lancet Infectious Diseases , marks the first peer-reviewed evaluation of the vaccine,  Ervebo , under real-world conditions.


The two-dose regimen of Ad26.ZEBOV and MVA-BN-Filo, sold under the brand names Zabdeno and Mvabea, [ 5 ] [ 7 ]  was developed by  Johnson & Johnson  at its  Janssen Pharmaceutical  company. It was approved for medical use in the European Union in July 2020. [ 38 ] [ 5 ] [ 7 ]


The regimen consists of two vaccine components (first vaccine as prime, followed by a second vaccine as  boost ) [ 39 ]  – the first based on AdVac technology from  Crucell  Holland B.V. (which is part of Janssen), the second based on the MVA-BN technology from  Bavarian Nordic . The Ad26.ZEBOV is derived from human adenovirus serotype 26 (Ad26) expressing the Ebola virus Mayinga variant glycoprotein, while the second component MVA-BN is the  Modified Vaccinia Virus Ankara  – Bavarian Nordic (MVA-BN) Filo-vector. [ 40 ]  This product commenced Phase I  clinical trial  at the  Jenner Institute  in Oxford during January 2015. [ 41 ] [ 42 ]  The preliminary data indicated the prime-boost vaccine regimen elicited temporary immunologic response in the volunteers as expected from vaccination.  The Phase II trial enrolled 612 adult volunteers and commenced in July 2015, in the United Kingdom and France.  A second Phase II trial, involving 1,200 volunteers, was initiated in Africa [ 39 ]  with the first trial commenced in Sierra Leone in October 2015. [ 43 ]


In September 2019, the  Committee for Medicinal Products for Human Use  (CHMP) of the  European Medicines Agency  (EMA) granted an accelerated assessment to Janssen for Ad26.ZEBOV and MVA-BN-Filo, [ 44 ]  and in November 2019, Janssen submitted a  Marketing Authorization Application  (MAA) to the EMA for approval of Ad26.ZEBOV and MVA-BN-Filo. [ 44 ] [ 45 ]


In May 2020, the EMA CHMP recommended granting a marketing authorization for the combination of Ad26.ZEBOV (Zabdeno) and MVA-BN-Filo (Mvabea) vaccines. [ 46 ] [ 47 ] [ 48 ]  Zabdeno is given first and Mvabea is administered approximately eight weeks later as a booster. [ 46 ]  This prophylactic two-dose regimen is therefore not suitable for an outbreak response where immediate protection is necessary. [ 46 ]  As a precautionary measure for individuals at imminent risk of exposure to Ebola virus (for example healthcare professionals and those living in or visiting areas with an ongoing Ebola virus disease outbreak), an extra Zabdeno booster vaccination should be considered for individuals who completed the Zabdeno-Mvabea two-dose vaccination regimen more than four months ago. [ 46 ]  Efficacy for humans is not yet known as the efficacy has been extrapolated from animal studies. [ 49 ]


In late 2014 and early 2015,  a double-blind, randomized Phase I trial was conducted in the  Jiangsu Province  of China; the trial examined a vaccine that contains  glycoproteins  of the 2014 strain, rather than those of the 1976 strain. The trial found signals of efficacy and raised no significant safety concerns. [ 50 ]


In 2017, the  China Food and Drug Administration  (CFDA) announced approval of an Ebola vaccine, co-developed by the Institute of Biotechnology of the  Academy of Military Medical Sciences  and the private vaccine-maker  CanSino Biologics . [ 51 ] [ 52 ]  It contains a human  adenovirus  serotype 5 vector (Ad5) with the glycoprotein gene from ZEBOV. [ 53 ]  Their findings were consistent with previous tests on rVSV-ZEBOV in Africa and Europe. [ 54 ]


In September 2014, two Phase I clinical trials began for the vaccine  cAd3-EBO Z , which is based on an attenuated version of a chimpanzee  adenovirus  (cAd3) that has been genetically altered so that it is unable to replicate in humans. [ 62 ]  The cAd3 vector has a DNA fragment insert that encodes the Ebola virus glycoprotein, which is expressed on the virion surface and is critical for attachment to host cells and catalysis of membrane fusion. [ 63 ]  It was developed by  NIAID  in collaboration with Okairos, now a division of  GlaxoSmithKline . For the trial designated VRC 20, 20 volunteers were recruited by the NIAID in Bethesda, Maryland, while three dose-specific groups of 20 volunteers each were recruited for trial EBL01 by University of Oxford, UK. Initial results were released in November 2014; all 20 volunteers developed antibodies against Ebola and there were no significant concerns raised about safety. [ 64 ] [ 65 ]  In December 2014, University of Oxford expanded the trial to include a booster vaccine based on MVA-BN, a strain of  Modified vaccinia Ankara , developed by  Bavarian Nordic , to investigate whether it can help increase immune responses further. [ 66 ] [ 67 ]   The trial which has enrolled a total of 60 volunteers will see 30 volunteers vaccinated with the booster vaccine. As of April 2015 [update] , Phase III trial with a single dose of cAd3-EBO Z begins in Sierra Leone after a successful Phase 2 study in West Africa countries. [ 25 ] [ 68 ]


At the 8th Vaccine and ISV Conference in Philadelphia on 27−28 October 2014,  Novavax  Inc. reported the development in a "few weeks" of a  glycoprotein  (GP)  nanoparticle  Ebola virus (EBOV GP) vaccine using their proprietary  recombinant  technology. A recombinant protein is a protein whose code is carried by  recombinant DNA . The vaccine is based on the newly published genetic sequence [ 69 ]  of the 2014  Guinea Ebola  (Makona) strain that is responsible for the 2014 Ebola disease epidemic in West Africa.  In animal studies, a useful immune response was induced and was found to be enhanced ten to a hundred-fold by the company's "Matrix-M"  immunologic adjuvant .  A study of the response of non-human primate to the vaccine had been initiated.  As of February 2015 [update] , Novavax had completed two primate studies on baboons and macaques and had initiated a Phase I clinical trial in Australia. The Lipid nanoparticle (LNP)-encapsulated  siRNAs  rapidly adapted to target the Makona outbreak strain of EBOV and are able to protect 100% of  rhesus monkeys  against lethal challenge when treatment was initiated at three days post-exposure while animals were viremic and clinically ill. [ 70 ]
The top line Phase I human trial results showed that the adjuvanted Ebola GP Vaccine was highly immunogenic at all dose levels. [ medical citation needed ]


On 5 November 2014, the  Houston Chronicle  reported that a research team at the  University of Texas-Austin  was developing a nasal spray Ebola vaccine, which the team had been working on for seven years. [ 71 ]  The team reported in 2014, that in the nonhuman primate studies it conducted, the vaccine had more efficacy when delivered via nasal spray than by injection. [ 72 ]  As of November 2014 [update] , further development by the team appeared unlikely due to lack of funding. [ 71 ] [ 73 ]


Vaxart  Inc. is developing a vaccine technology in the form of a temperature-stable tablet which may offer advantages such as reduced  cold chain  requirement, and rapid and scalable manufacturing. In January 2015, Vaxart announced that it had secured funding to develop its Ebola vaccine to Phase I trial. [ 74 ]


A study published in  Science  during March 2015, demonstrated that vaccination with a weakened form of the Ebola virus provides some measure of protection to non-human primates. This study was conducted in accordance with a protocol approved by an Institutional Animal Care and Use Committee of the National Institutes of Health. [ 75 ]  The new vaccine relies on a strain of Ebola called EBOVΔVP30, which is unable to replicate. [ 61 ]


A study published in  Human Vaccines & Immunotherapeutics  in March 2017, analyzing data from a clinical trial of the GamEvac-Combi vaccine in Russia, concluded said vaccine to be safe and effective and recommended proceeding to Phase III trials. [ 76 ]


In September 2019, a study published in  Cell Reports  demonstrated the role of the Ebola virus VP35 protein in its immune evasion. A recombinant form of Ebola virus with a mutant VP35 protein (VP35m) was developed, and showed positive results in the activation of the RIG-I-like receptor signaling. Non-human primates were challenged with different doses of VP35. This challenge resulted in the activation of the innate immune system and the production of anti-EBOV antibodies. The primates were then back-challenged with the wild type Ebola virus and survived. This potentially creates a prospect for a future vaccine development. [ 77 ]


In January 2015, Marie-Paule Kieny, the  World Health Organization 's (WHO) assistant director-general of health systems and innovation, announced that the vaccines cAd3-EBO Z and VSV-EBOV had demonstrated acceptable safety profiles during early testing and would soon progress to large-scale trials in Liberia, Sierra Leone, and Guinea. The trials would involve up to 27,000 people and comprise three groups – members of the first two groups would receive the two candidate vaccines, while the third group will receive a  placebo . [ 78 ]   Both vaccines have since successfully completed the  Phase 2  studies.  The large scale  Phase 3  studies have begun as of April 2015 [update] , in Liberia and Sierra Leone, [ 25 ] [ 68 ]  and in Guinea in March 2016. [ 28 ]


In addition, a medical anthropologist at  Université de Montréal , had been working in Guinea and raised further questions about safety in the ring trial after spending time in April at one of the Ebola treatment units where trial participants are taken if they become ill, the centre in Coyah, about 50   km from the capital of Conakry. [ 23 ]


The  Russian Foreign Ministry  announced in 2016, the intention to conduct field trials of two Russian vaccines involving 2000 people. [ 79 ]  According to local media reports, the Guinean government authorized the commencement of the trials on 9 August 2017, at the  Rusal -built Research and Diagnostic Center of Epidemiology and Microbiology in  Kindia . The trials were slated to continue until 2018. [ 79 ] [ 80 ]  As of October 2019, Russia licensed the vaccine by local regulatory authorities and was reportedly ready to ship vaccine to Africa. [ 81 ]


In 2014,  Credit Suisse  estimated that the US government will provide over $1   billion in contracts to companies to develop medicine and vaccines for Ebola virus disease. [ 82 ]  Congress passed a law in 2004 that funds a national stockpile of vaccines and medicine for possible outbreaks of disease. [ 82 ]  A number of companies were expected to develop Ebola vaccines:  GlaxoSmithKline ,  NewLink Genetics ,  Johnson & Johnson , and  Bavarian Nordic . [ 82 ]  Another company,  Emergent BioSolutions , was a contestant for manufacturing new doses of  ZMapp , [ citation needed ]  a drug for Ebola virus disease treatment originally developed by  Mapp Biopharmaceutical . [ 83 ]  Supplies of ZMapp ran out in August 2014. [ 84 ]  In September 2014, the  Biomedical Advanced Research and Development Authority  (BARDA) entered into a multimillion-dollar contract with Mapp Biopharmaceutical to accelerate the development of ZMapp. [ 85 ]  Additional contracts were signed in 2017. [ 86 ]


Four laboratory-confirmed cases of  Ebola virus disease  (commonly known as "Ebola") occurred in the  United States  in 2014. [ 3 ]  Eleven cases were reported, including these four cases and seven cases medically evacuated from other countries. [ 4 ]  The first was reported in September 2014. [ 5 ]  Nine of the people contracted the disease outside the US and traveled into the country, either as regular airline passengers or as  medical evacuees ; of those nine, two died. Two people contracted Ebola in the United States. Both were nurses who treated an Ebola patient; both recovered. [ 4 ]


On September 30, 2014, the  Centers for Disease Control and Prevention  (CDC) announced that  Thomas Eric Duncan , a 45-year-old  Liberian  national visiting the United States from  Liberia , had been diagnosed with  Ebola  in  Dallas, Texas . [ 6 ] [ 7 ]
Duncan, who had been visiting family in Dallas, was treated at  Texas Health Presbyterian Hospital Dallas . [ 8 ] [ 9 ]  By October 4, his condition had deteriorated from "serious but stable" to "critical". [ 10 ]  On October 8, he died of Ebola. [ 11 ]  The other three cases diagnosed in the United States as of October 2014 [update]  were:


Hundreds of people were tested or monitored for potential  Ebola virus  infection, [ 16 ]  but the two nurses were the only confirmed cases of locally transmitted Ebola. Public health experts and the  Obama  administration opposed instituting a travel ban on Ebola endemic areas, stating that it would be ineffective and would paradoxically worsen the situation. [ 17 ]


No one who contracted Ebola while in the United States died from it. No new cases were diagnosed in the United States after Spencer was released from Bellevue Hospital on November 11, 2014. [ 18 ]


Thomas Eric Duncan  was from  Monrovia, Liberia , to date the country hit hardest by the  Ebola virus epidemic . [ 19 ]  He worked as a personal driver for the general manager of Safeway Cargo, a  FedEx  contractor in Liberia. [ 20 ]  According to manager Henry Brunson, Duncan had abruptly quit his job on September 4, 2014, giving no reason. [ 21 ]


On September 15, 2014, the family of Marthalene Williams, who later died of  Ebola virus disease , could not call an ambulance to transfer the pregnant Williams to a hospital. Duncan, their tenant, helped to transfer Williams by taxi to an Ebola treatment ward in Monrovia. Duncan rode in the taxi to the treatment ward with Williams, her father and her brother. [ 22 ]


On September 19, Duncan went to  Monrovia Airport , where, according to Liberian officials, he lied about his history of contact with the disease on an airport questionnaire before boarding a  Brussels Airlines  flight to  Brussels . In Brussels, he boarded  United Airlines  Flight 951  to  Washington Dulles Airport . [ 23 ]  From Dulles, he boarded  United Airlines  Flight 822 to Dallas/Fort Worth. He arrived in Dallas at 7:01 p.m. CDT [ 24 ]  on September 20, 2014, [ 8 ] [ 9 ]  and stayed with his partner and her five children, who lived in the Fair Oaks apartment complex in the  Vickery Meadow  neighborhood of Dallas. [ 25 ] [ 26 ]   Vickery Meadow , the neighborhood in Dallas where Duncan lived, has a large African immigrant population and is Dallas's densest neighborhood. [ 27 ]


Duncan began experiencing symptoms on September 24, 2014, and arrived at the  Texas Health Presbyterian Hospital  emergency room at  10:37 p.m.  on September 25. [ 28 ]  At  11:36 p.m. , a triage nurse asked him about his symptoms, and he reported feeling "abdominal pain, dizziness, nausea and headache (new onset)". [ 28 ]  The nurse recorded a fever of 100.1 °F (37.8 °C), but did not inquire as to his travel history as this was not triage protocol at the time. [ 28 ]  At  12:05 a.m. , Duncan was admitted into a treatment area room where the on-duty physician accessed the  electronic health record  (EHR). The physician noted nasal congestion, a runny nose, and abdominal tenderness. Duncan was given  paracetamol  (acetaminophen) at  1:24 a.m. [ 28 ]   CT scan  results came back noting "no acute disease" for the abdominal and pelvic areas and "unremarkable" for the head. [ 28 ]  Lab results returned showing slightly low  white blood cells , low  platelets , increased  creatinine , and elevated levels of the liver enzyme  AST . [ 28 ] [ 29 ]  His temperature was noted at 103.0 °F (39.4 °C) at  3:02 a.m.  and 101.2 °F (38.4 °C) at  3:32 a.m.  Duncan was diagnosed with  sinusitis  and abdominal pain and sent home at  3:37 a.m.  with a prescription for  antibiotics , which are not effective for treating  viral diseases . [ 28 ] [ 30 ]


What we're seeing now is not an "outbreak" or an "epidemic" of Ebola in America. This is a serious disease, but we can't give in to hysteria or fear. – President Barack Obama on the Ebola outbreak


Duncan's condition worsened, and he was transported on September 28 to the same Texas Health Presbyterian Hospital emergency room by ambulance. [ 31 ] [ 32 ]  He arrived in the emergency room at  10:07 a.m. , experiencing diarrhea, abdominal pain, and fever. [ 33 ]  Within fifteen minutes, a doctor noted that Duncan had recently come from Liberia and needed to be tested for Ebola. The doctor described following "strict [CDC] protocol" including wearing a mask, gown, and gloves. At  12:58 p.m. , the doctor called the CDC directly. By  9:40 p.m. , Duncan was experiencing explosive diarrhea and projectile vomiting. [ 33 ]  At  8:28 a.m.  the next morning, the doctor noted that he "appeared to be deteriorating". By  11:32 a.m. , he was severely fatigued, enough to prevent him from using the bedside toilet. [ 33 ]  Later that day, he was transferred to an  intensive care unit  (ICU) after all other patients had been evacuated. The next day, September 30, he was diagnosed with Ebola virus disease after a positive test result. [ 33 ]


Duncan's diagnosis was publicly confirmed during a CDC news conference the same day. [ 34 ] [ 35 ]  That evening, Duncan reported feeling better and requested to watch a movie. The following morning, he was breathing rapidly and complaining of "pain all over". [ 33 ]  By the afternoon, however, he was able to eat, and the doctor noted that he was feeling better. The next day, October 3, he again reported feeling abdominal pain. That evening, the hospital contacted  Chimerix , a biotechnology company developing  Brincidofovir  to combat the disease. The next day, Duncan's  organs were failing , and he was  intubated  to help him breathe. In the afternoon, the hospital began administering Brincidofovir. [ 36 ] [ 37 ]  Nurses Nina Pham and Amber Joy Vinson continued to care for Duncan around the clock. On October 7, the hospital reported that Duncan's condition was improving. [ 38 ]  However, he died at  7:51 a.m.  on October 8, becoming the first person to die in the United States of Ebola virus disease and the index patient for the later infections of nurses Pham and Vinson. [ 39 ] [ 40 ]


On October 5, the CDC announced it had lost track of a homeless man who had been in the same ambulance as Duncan. They announced efforts were underway to find the man and place him in a comfortable and compassionate monitoring environment. Later that day, the CDC announced that the man had been found and was being monitored. [ 41 ]


Up to 100 people may have had contact with those who had direct contact with Duncan after he showed symptoms. Health officials later monitored 50 low- and 10 high-risk contacts, the high-risk contacts being Duncan's close family members and three ambulance workers who took him to the hospital. [ 42 ]  Everyone who came into contact with Duncan was being monitored daily to watch for symptoms of the virus, [ 43 ]  until October 20, when health officials removed 43 out of the 48 initial contacts of Thomas Duncan from isolation. [ 44 ]   On November 7, 2014, Dallas was officially declared "Ebola free" after 177 monitored people cleared the 21 day threshold without becoming ill. [ 45 ]


On October 2, Liberian authorities said they could prosecute Duncan if he returned because before flying he had filled out a form in which he had falsely stated he had not come into contact with an Ebola case. [ 46 ]  Liberian President  Ellen Johnson Sirleaf  told the  Canadian Broadcasting Corporation  she was angry with Duncan for what he had done, especially given how much the United States was doing to help tackle the crisis: "One of our compatriots didn't take due care, and so, he's gone there and in a way put some Americans in a state of fear, and put them at some risk, and so I feel very saddened by that and very angry with him. ... The fact that he knew (he might be a carrier) and he left the country is unpardonable, quite frankly." [ 47 ]
Before his death, Duncan brazenly claimed that he did not know at the time of boarding the flight that he had been exposed to Ebola; he said he believed the woman he helped was having a miscarriage, which contradicts corroborated accounts from family members who also helped transport the woman to an Ebola ward. [ 22 ] [ 48 ]


Duncan's family said the care Duncan received was at best "incompetent" and at worst "racially motivated". [ 49 ]  Family members threatened legal action against the hospital where Duncan received treatment. [ 50 ]  In response, Texas Health Presbyterian Hospital issued a statement, "Our care team provided Mr. Duncan with the same high level of attention and care that would be given any patient, regardless of nationality or ability to pay for care. We have a long history of treating a multicultural community in this area." [ 51 ]  The hospital spent an estimated $500,000 to treat the uninsured Duncan. [ 52 ]


Officials at Texas Presbyterian Hospital reported that patients' cancellation of elective surgeries and potential emergency patients' preference for other hospitals' emergency rooms had left their hospital looking like a "ghost town". [ 53 ]


The reaction to the care and treatment of Thomas Duncan, and the subsequent transmission to two of the nurses on his care team, caused several hospitals to question the extent to which they are obligated to treat Ebola patients.  Their concern surrounds the reality that understaffed and poorly equipped hospitals performing invasive procedures, like renal dialysis and intubation, both of which Duncan received at Texas Presbyterian, could put staff at too much risk for contracting the virus.  Emory University Hospital  in Atlanta also used renal dialysis in treating patients at their biocontainment unit, but no health care workers became infected. [ 54 ]  In October 2014 Vickery Meadow residents stated that people were discriminating against them because of the incident. [ 55 ]


On the night of October 10, Nina Pham, a 26-year-old nurse who had treated Duncan at Texas Health Presbyterian Hospital, reported a low-grade fever and was placed in isolation. On October 11, she tested positive for Ebola virus, becoming the first person to contract the virus in the U.S. On October 12, the CDC confirmed the positive test results. [ 12 ]   Hospital officials said Pham had worn the recommended protective gear when treating Duncan on his second visit to the hospital and had "extensive contact" with him on "multiple occasions". Pham was in stable condition as of October 12. [ 12 ] [ 56 ] [ 57 ]


On October 16, Pham was transferred to the  National Institutes of Health Clinical Center  in  Bethesda, Maryland . [ 58 ]  On October 24, the NIH declared Pham free of the Ebola virus. [ 59 ]  That day Pham traveled to the White House where she met with President Obama. [ 60 ]