Tom Frieden , director of the  Centers for Disease Control and Prevention , initially blamed a breach in protocol for the infection. [ 61 ]  The hospital's chief clinical officer, Dr. Dan Varga, said all staff had followed CDC recommendations. Bonnie Costello of  National Nurses United  said, "You don't scapegoat and blame when you have a disease outbreak. We have a system failure. That is what we have to correct." [ 62 ]  Frieden later spoke to "clarify" that he had not found "fault with the hospital or the healthcare worker". [ 63 ]  National Nurses United criticized the hospital for its lack of Ebola protocols and for guidelines that were "constantly changing". [ 64 ]  Briana Aguirre, a nurse who had cared for Nina Pham, criticized the hospital in an appearance on NBC's  Today Show . Aguirre said that she and others had not received proper training or  personal protective equipment , and that the hospital had not provided consistent protocols for handling potential Ebola patients into the second week of the crisis. [ 65 ]  A report indicated that healthcare workers did not wear hazmat suits until Duncan's test results confirmed his infection due to Ebola, two days after his admission to the hospital. [ 66 ]  Frieden later said that the CDC could have been more aggressive in the management and control of the virus at the hospital. [ 67 ]


On March 2, 2015  The New York Times  reported that Pham filed a suit against  Texas Health Resources , her hospital's parent company, accusing it of "negligence, fraud and invasion of privacy". [ 68 ]  Pham was described as still experiencing numerous physical and psychological problems, listing lack of proper training as the reason for her illness. [ 68 ]


On October 14, a second nurse at the same hospital, identified as 29-year-old Amber Vinson, [ 69 ]  reported a  fever . Amber Joy Vinson [ 70 ]  was among the nurses who had provided treatment for Duncan. Vinson was isolated within 90 minutes of reporting the fever. By the next day, Vinson had tested positive for Ebola virus. [ 71 ]  On October 13, Vinson had flown  Frontier Airlines  Flight 1143 from Cleveland to Dallas, after spending the weekend in  Tallmadge  and  Akron, Ohio . Vinson had an elevated temperature of 99.5 °F (37.5 °C) before boarding the 138-passenger jet, according to public health officials. Vinson had flown to Cleveland from Dallas on  Frontier Airlines  Flight 1142 on October 10. [ 72 ]  Flight crew members from Flight 1142 were put on paid leave for 21 days. [ 73 ]


During a press conference, CDC Director Tom Frieden stated she should not have traveled since she was one of the health care workers known to have had exposure to Duncan. [ 74 ]  Passengers of both flights were asked to contact the CDC as a precautionary measure. [ 75 ] [ 76 ] [ 77 ]


It was later discovered that the CDC had, in fact, given Vinson permission to board a commercial flight to Cleveland. [ 78 ]  Before her trip back to Dallas, she spoke to Dallas County Health Department and called the CDC several times to report her 99.5 °F (37.5 °C) temperature before boarding her flight. A CDC employee who took her call checked a CDC chart, noted that Vinson's temperature was not a true fever – a temperature of 100.4 °F (38.0 °C) or higher – which the CDC deemed as "high risk", and let her board the commercial flight. [ 79 ] [ 80 ]  On October 19, Vinson's family released a statement detailing her government-approved travel clearances and announcing that they had hired a Washington, DC, attorney,  Billy Martin . [ 81 ]  As a precaution, sixteen people [ 82 ]  in Ohio who had had contact with Vinson were voluntarily quarantined. On October 15, Vinson was transferred to the  Emory University Hospital  in Atlanta. [ 83 ]  Seven days later, Vinson was declared Ebola free by Emory University Hospital. [ 84 ]


As of October 15, 2014 [update] , there were 76 Texas Presbyterian Hospital health care workers being monitored because they had had some level of contact with Thomas Duncan. [ 85 ]  On October 16, after learning that Vinson had traveled on a plane before her Ebola diagnosis, the  Texas Department of State Health Services  advised all health care workers exposed to Duncan to avoid travel and public places until 21 days after their last known exposure. [ 86 ]


On October 23, Craig Spencer, [ 14 ]  a physician who treated Ebola patients in West Africa, tested positive for Ebola at  Bellevue Hospital Center  after having a 100.3 °F (37.9 °C)  fever . Officials said he was hospitalized with fever, nausea, pain, and fatigue. [ 87 ]  He had flown to  New York City  from Guinea within the previous ten days, [ 88 ]  and contacted the city's  Department of Health  and  Doctors without Borders  after showing symptoms. [ 89 ] [ 90 ]  Dr. Spencer traveled to Guinea to treat Ebola victims on September 16 and returned on October 16. He had been self-monitoring for symptoms of the disease, and began to feel sluggish on October 21, but did not show any symptoms for two days. [ 91 ]  His case was the first to be diagnosed in New York. [ 92 ]  The city was trying to find people who may have been in contact with Dr. Spencer between October 21 and 23. [ 14 ]


On October 22, the day before he had symptoms, Dr. Spencer rode the  New York City Subway , walked on the  High Line  park, went to a bowling alley and a restaurant in  Brooklyn , took an  Uber  to his home in  Manhattan , and took a 3-mile (4.8 km) jog in  Harlem  near where he lived. [ 93 ] [ 94 ]  Three other people who were with Dr. Spencer in the previous few days were quarantined as well. [ 95 ]  Dr. Spencer's apartment and the bowling alley he went to were cleaned by hazmat company  Bio Recovery Corporation . [ 96 ] [ 97 ]  Health officials stated it was unlikely that Dr. Spencer could have transmitted the disease through subway poles, hand railings, or via bowling balls. [ 98 ] [ 99 ]


New York hospitals, health-workers, and officials had conducted weeks of drills and training in preparation for patients like Dr. Spencer. Upon arrival at the hospital, he was put in a specially designed isolation center for treatment. Not many details about the treatment were given, except that he participated in decisions relating to his medical care. [ 100 ]  On October 25, the  New York Post  reported that an anonymous source had said that nurses at Bellevue had been calling in sick to avoid having to care for Spencer. A hospital spokesperson denied there was a sick out. [ 101 ]  On November 1, his condition was upgraded to "stable", [ 102 ]  and on November 7 the hospital announced he was free of Ebola. [ 103 ]  Spencer was released from the hospital on November 11. [ 104 ]  He was cheered and applauded by medical staff members, and hugged by the Mayor of New York,  Bill de Blasio  as he walked out of the hospital. The Mayor also declared: "New York City is Ebola free". [ 87 ]


As a result of Dr. Spencer's Ebola case, U.S. Senator  Charles Schumer  (D-NY), proposed an Ebola fund in an  omnibus bill  to be considered in fiscal year 2015. Schumer said the funds were needed to compensate New York City, as well as other cities treating Ebola patients, in the same way the federal government covers communities that suffer after a natural disaster. Schumer said Dr. Spencer's care at Bellevue Hospital involved around 100 health care workers. In addition, the city's health department established a 24-hour-a-day operation involving 500 staffers to keep track of the approximately 300 persons from West Africa hot spots who arrive in New York every day. [ 105 ]


By the time the  Ebola virus epidemic in West Africa  was over in June 2016, seven Americans had been evacuated to the U.S. for treatment after contracting  Ebola virus  while working with medical teams trying to stop the epidemic. [ 106 ]
 Kent Brantly , a physician and medical director in Liberia for the aid group  Samaritan's Purse , and co-worker Nancy Writebol were infected in July 2014, while working in  Monrovia . [ 107 ] [ 108 ] [ 109 ]  Both were flown to the United States at the beginning of August via the CDC's  Aeromedical Biological Containment System  for further treatment in  Atlanta 's  Emory University Hospital . [ 110 ]  On August 21, Brantly and Writebol recovered and were discharged. [ 111 ]  Brantly has since donated blood to three others with Ebola (Sacra, Mukpo and Pham). [ citation needed ]


On September 4, a Massachusetts physician, Rick Sacra, was airlifted from Liberia to be treated in  Omaha, Nebraska  at the  Nebraska Medical Center . Working for  Serving In Mission  (SIM), he was the third U.S. missionary to contract Ebola. [ 112 ]  He thought that he probably contracted Ebola while performing a  Caesarean section  on a patient who had not been diagnosed with the disease. While in hospital, Sacra received a blood transfusion from Brantly, who had recently recovered from the disease. On September 25, Sacra was declared Ebola-free and released from the hospital. [ 113 ]


On September 9, the fourth U.S. citizen who contracted the Ebola virus arrived at Emory University Hospital in Atlanta for treatment. On October 16, he released a statement saying he had improved and expected to be discharged in the near future. The doctor was identified as  Ian Crozier , and according to the hospital, the sickest patient treated. [ 114 ] [ 115 ] [ 116 ]  He was scheduled to receive a blood or  serum  transfusion from a British man who had recently recovered from the disease. [ 117 ]  In addition, on September 21, a CDC employee, who showed no symptoms of the disease, was flown back to the United States as a preventive measure after low-risk exposure with a healthcare worker; he posed no risks to his family or the United States, and he is not known to have died. [ 118 ]  On September 28, a fourth American doctor was admitted to National Institutes of Health hospital. [ 119 ]


On October 2,  NBC News  photojournalist Ashoka Mukpo, covering the outbreak in Liberia, tested positive for Ebola after showing symptoms. [ 120 ]  Four other members of the NBC team, including physician  Nancy Snyderman , were being closely monitored for symptoms. [ 121 ]  Mukpo was evacuated on October 6 to the  University of Nebraska Medical Center  for treatment in their isolation unit. [ 106 ]  On October 21, Mukpo was declared Ebola-free and allowed to return to his home in Rhode Island. [ 122 ]


A government official in Sierra Leone announced on November 13, that a doctor from Sierra Leone, a  permanent resident  of the United States married to a U.S. citizen, would be transported to the Nebraska Medical Center for treatment for Ebola. [ 123 ] [ 124 ]  The doctor, identified later as Martin Salia, became symptomatic while in Sierra Leone. His initial Ebola test came back negative, but his symptoms persisted. He attempted to treat his symptoms, which included vomiting and diarrhea, believing he had malaria. A second test for Ebola came back positive. His family expressed concern that the delay in diagnosis might have impacted his recovery. [ 125 ]  Salia arrived at  Eppley Airfield  in Omaha on November 15, and was transported to the Nebraska Medical Center. According to the team that assisted in the transport, he was critically ill and considered to be the sickest patient to be evacuated, but stable enough to fly. [ 126 ]  On November 17, Salia died from the disease. Dr. Philip Smith, medical director of the biocontainment unit at Nebraska Medical Center, said Salia's disease was already "extremely advanced" by the time he arrived in Omaha. By then, Salia's kidneys had failed and he was in acute respiratory distress. Salia's treatment included a blood plasma transfusion from an Ebola survivor, as well as the experimental drug  ZMapp . Salia had been working as a general surgeon in  Freetown , Sierra Leone when he fell ill. It was not clear when or where he had had contact with Ebola patients. [ 127 ]


A U.S. clinician contracted Ebola while working in Port Loko, Sierra Leone. He collapsed in the hospital and colleagues who assisted him were monitored for exposure. He was diagnosed with Ebola on March 10, 2015, and medically evacuated to the National Institutes of Health in Bethesda, Maryland on March 13. [ 128 ]  His condition was downgraded from serious to critical on March 16. [ 129 ]  The ten exposed colleagues were flown back to the U.S., going into isolation near the Ebola-rated hospitals at Nebraska, Georgia, and Maryland. [ 130 ]  On March 26, 2015, the NIH upgraded the medically evacuated health worker being treated in Bethesda from critical to serious. A further 16 volunteers were monitored for possible exposure. [ 131 ]  On April 9, 2015, the clinician was upgraded to good condition and discharged. [ 132 ]   He was treated by Dr. Anthony Fauci, who later said he was "the sickest person he had ever treated, who recovered."  This patient revealed his identity in late 2019 as Preston Gorman, a physician assistant.  [ 133 ] [ 134 ]


The U.S. military released plans to send up to 4,000 troops to West Africa to establish treatment centers starting September 29. The troops are tasked with building modular hospitals known as  Expeditionary Medical Support Systems  (EMEDS). Plans included building a 25-bed hospital for health care workers and 17 treatment centers with 100 beds each in Liberia. [ 135 ]  By the end of September 2014 150 military personnel were helping USAID in the capital, Monrovia. [ 136 ]


U.S. Army chief of staff  Ray Odierno  ordered on October 27 a 21-day quarantine of all soldiers returning from Operation United Assistance. Up to 12 soldiers were quarantined in a U.S. base in Italy. [ 137 ]


Since 2007, US hospitals have relied on  CDC  infection control protocols to contain Ebola virus disease. Until October 20, 2014, the CDC guidelines allowed hospitals wide latitude to select gear based on interaction between healthcare workers and patients and on the mode of transmission of the disease being handled. The guidelines suggested gowns with "full coverage of the arms and body front, from neck to the mid-thigh or below, will ensure that clothing and exposed upper body areas are protected", and additionally recommend masks and goggles. [ 138 ] [ 139 ]


Some infection control experts [ who? ]  said that many American hospitals improperly trained their personnel to handle Ebola cases because they were following federal guidelines that were too lax. US officials abruptly changed their guidelines on October 14.  The New York Times  stated that this was an effective acknowledgment that there were problems with the procedures for protecting health care workers. Sean Kaufman, who oversaw infection control at Emory University Hospital while it treated Ebola patients, has said the previous CDC guidelines were "absolutely irresponsible and dead wrong". Kaufman called to warn the agency about its lax guidelines but, according to Kaufman, "They kind of blew me off." [ 140 ]


A  Doctors Without Borders  representative, whose organization has been treating Ebola patients in Africa, criticized a CDC poster for lax guidelines on containing Ebola, saying, "It doesn't say anywhere that it's for Ebola. I was surprised that it was only one set of gloves, and the rest bare hands. It seems to be for general cases of infectious disease." [ 140 ]


The national nursing union  National Nurses United  criticized the CDC for making the guidelines voluntary. There were complaints at the Texas hospital that healthcare professionals had to use tape to cover their exposed necks. [ 140 ]  According to Frieden, the CDC is appointing a hospital site manager to oversee Ebola containment efforts and are making "intensive efforts" to retrain and supervise staff. [ 138 ]


On October 14, the WHO reported that 125 contacts in the United States were being traced and monitored. [ 141 ]  On October 20, the CDC updated its guidance on  personal protective equipment  with new detailed instructions that include specifying that no skin should be exposed and adding extensive instructions for donning and doffing the equipment. [ 142 ]  On October 20 CDC updated its guidance to add clarification that Ebola may spread through wet droplets such as sneezes. [ 143 ] [ 144 ] [ 145 ]


In mid-October 2014, President Barack Obama appointed  Ron Klain  as the "Ebola response coordinator" of the United States. Klain is a lawyer who previously served as chief of staff to vice presidents  Al Gore  and  Joe Biden . [ 146 ]  Klain had no medical or health care experience. [ 147 ]  After criticism, Obama said, "It may make sense for us to have one person ... so that after this initial surge of activity, we can have a more regular process just to make sure that we're crossing all the T's and dotting all the I's going forward". Klain reported to Homeland Security Adviser  Lisa Monaco  and National Security Advisor  Susan Rice . [ 148 ] [ 149 ] [ 150 ] [ 151 ]  Klain did not coordinate with hospitals and the  United States Public Health Service , as this was the responsibility of  Nicole Lurie , Assistant Secretary for Preparedness and Response. [ 152 ]  President Barack Obama attempted to calm public fears by hugging nurse Nina Pham who had been cured of Ebola. [ 153 ]


President Obama announced the formation of rapid response teams to travel to hospitals with newly diagnosed patients. A second set of teams will prep hospitals in cities deemed most likely to see an Ebola virus case. Three of those teams are already operating. In announcing the formation of the teams, President Obama explained, "We want a rapid response team, a SWAT team essentially, from the CDC to be on the ground as quickly as possible, hopefully within 24 hours, so that they are taking the local hospital step by step through what needs to be done." The CDC has developed two sets of teams, identified by the acronyms CERT (CDC Ebola Response Team) and FAST (Facility Assessment and Support Teams). The CERTs have 10 to 20 people each, who can be sent to a hospital with a suspected and/or laboratory confirmed Ebola virus case. The teams are drawn from 100 CDC workers and others. The FAST teams assist hospitals that have indicated they are willing to take on Ebola cases. [ 154 ]


Starting in October 2014, U.S. government officials began questioning airplane passengers and screening them for fever at five U.S. airports:   John F. Kennedy International Airport  in New York,  Newark Liberty International Airport  in New Jersey,  O'Hare International Airport  in Illinois,  Washington Dulles International Airport  in Virginia, and  Hartsfield–Jackson Atlanta International Airport  in Georgia. [ 155 ]   Combined, these airports receive more than 94% of passengers from Guinea, Liberia, and Sierra Leone, the three countries most affected by Ebola. [ 155 ] [ 156 ]


Although no plans have been announced for other airports, screening in the U.S. represents a second layer of protection since passengers are already being screened upon exiting these three countries. However, the risk can never be eliminated. [ 157 ]   On October 21, the  Department of Homeland Security  announced that all passengers from Liberia, Sierra Leone, and Guinea will be required to fly into one of these five airports. [ 158 ]  On October 23, the CDC announced that all passengers from these countries would receive 21-day monitoring. [ 159 ]


A physician with the  WHO ,  Aileen Marty , who had spent 31 days in  Nigeria , criticized the complete lack of screening for Ebola on her recent return to the United States through  Miami International Airport  on October 12. [ citation needed ]


There have also been calls by congressional leaders, including U.S. representative  Ed Royce , Chairman of the House Foreign Relations Committee, and U.S. representative  Michael McCaul  of Texas, Chair of the Homeland Security Committee, to suspend issuing visas to travelers from the affected West African countries, including Liberia, Sierra Leone, and Guinea. [ 160 ] [ 161 ]


On October 7, 2014,  Connecticut  governor  Dannel Malloy  signed an order authorizing the mandatory  quarantine  for 21 days of anyone, even if asymptomatic, who had direct contact with Ebola patients. [ 162 ] [ 163 ]  Nine people were quarantined on October 22, in accordance with the Connecticut order. [ 164 ]


At a joint news conference on October 24,  New York  governor  Andrew Cuomo  and  New Jersey  governor  Chris Christie  announced that they were imposing a mandatory 21-day quarantine on all air travelers returning to New York and New Jersey from West Africa who have had contact with Ebola patients. In explaining the move from the CDC's voluntary quarantine to a state ordered mandatory one, Cuomo cited the case of Dr. Spencer. "In a region like this, you go out three times, you ride the subway, you ride the bus, you could affect hundreds of people." Cuomo praised Dr. Spencer's work but stated, "He's a doctor and even he didn't follow the voluntary quarantine. Let's be honest." [ 165 ] [ 166 ]


Governors Cuomo and Christie stated that their two states needed to go beyond the federal CDC guidelines. Cuomo said Dr. Spencer's activity in the days before his diagnosis showed the guidelines, which includes urging health care workers and others who have had contact with Ebola patients to voluntarily quarantine themselves, were not enough. [ 165 ]


Late on October 26, Cuomo modified the state's quarantine procedure, stating that people entering New York who have had contact with Ebola patients in West Africa will be quarantined in their homes for the 21 days, with twice daily checks to ensure their health has not changed and that they are complying with the order, and would receive some compensation for lost wages, if any. [ 167 ]  President Obama and his staff had been attempting to persuade Cuomo, Christie, and the  government of Illinois [ 168 ]  to reverse their mandatory quarantines. [ 167 ]


Illinois governor  Pat Quinn  issued a similar quarantine authorization the same day as New York and New Jersey initially did, with  Florida  governor  Rick Scott  on October 25, authorizing mandatory twice daily monitoring for 21 days of people identified as coming from countries affected by Ebola. [ 169 ] [ 170 ]  Illinois health officials later said that only people at high risk of Ebola exposure, such as not wearing protective gear near Ebola patients, will be quarantined. [ 171 ]


Pennsylvania ,  Maryland , and  Georgia  have all authorized mandatory twice daily health monitoring and/or temperature reporting for 21 days for people exposed to people with Ebola.  Virginia  has also implemented mandatory twice daily temperature reporting and daily monitoring from health authorities, but has also authorized mandatory quarantine for higher risk patients. [ 172 ] [ 173 ]  California mandated a 21-day quarantine for all health workers who have had contact with Ebola patients. [ 174 ]


Kaci Hickox, an American nurse who treated Ebola patients in  Sierra Leone  became the first person placed under the new mandatory quarantine rules on her arrival at  Newark Liberty International Airport , in New Jersey. A low-accuracy (forehead) thermometer indicated Hickox developed a fever on Friday night and was taken to University Hospital in Newark. She later tested negative for the Ebola virus but remained quarantined in a medical tent. Hickox and Doctors Without Borders criticized the condition of the quarantine in a tent with a bed and a  portable toilet , but without shower facility. [ 175 ]  Hickox criticized her treatment as inhumane. [ 176 ]  The hospital responded that they tried their best to accommodate Hickox by allowing her to have computer access, cell phone, reading materials, and providing take-out food and drink. [ 177 ]  On October 27, after being symptom free for an additional 24-hour period, testing negative for Ebola, and after the state's quarantine policy was relaxed the night before, [ 167 ]  Hickox was released from quarantine in New Jersey. [ 178 ]  She has filed suit. [ 179 ]


Hickox was escorted out of New Jersey and into Maine the following day by a private convoy of SUVs. [ 180 ]   Maine  governor  Paul LePage  announced he was joining with his state's health department in seeking legal authority to enforce the quarantine after Hickox announced she would not comply with the isolation protocols in Maine. She left her house on October 29 and 30. [ 181 ]  The governor said: "She's violated every promise she's made so far, so I can't trust her. I don't trust her." [ 182 ]  A Maine judge ruled against a mandatory quarantine on October 31, but required Hickox to comply with "direct active monitoring", to coordinate her travel with Maine health officials, and to notify health officials if she develops symptoms of Ebola. [ 183 ]


On October 29, Texas governor  Rick Perry  announced that a Texas nurse returning from Sierra Leone where she treated Ebola patients, had agreed to self-quarantine at her  Austin  home for 21 days following her return to Texas, and undergo frequent monitoring from state health officials. although she did not have any symptoms of Ebola virus. The nurse was not named to protect her privacy. Perry spoke with the nurse over the phone to thank her for work to fight Ebola. [ 184 ]


U.S. Army Chief of Staff  Ray Odierno  also ordered on October 27 a 21-day quarantine of all soldiers returning from  Operation United Assistance  in Liberia. As many as 12 soldiers were quarantined in a U.S. base in Italy. [ 185 ]


On November 13, 2014, President Obama issued a  presidential memorandum , invoking a federal law to immunize contractors hired by the  U.S. Agency for International Development  (USAID) from liability "with respect to claims, losses, or damage arising out of or resulting from exposure, in the course of performance of the contracts, to Ebola" during the emergency period. [ 186 ]


There were numerous overreactions to the perceived threat of an Ebola outbreak, particularly on the part of school officials. On October 16, a building housing two schools in the  Solon City School District  near  Cleveland , Ohio, was closed for a single day of disinfection procedures after finding that a staff member may have been on the aircraft that  Amber Vinson  used on a previous flight. [ 187 ]  Another school in the  Cleveland Metropolitan School District  was disinfected overnight due to similar concerns but remained open. In both cases, affected staff were sent home until cleared by health officials. School officials said that they had been assured by city health officials that there was no risk and that  the disinfection was "strictly precautionary". [ 188 ]  Three schools in the  Belton Independent School District  in Belton, Texas, were also closed. Infectious disease experts considered these closures to be an overreaction and were concerned that it would frighten the public into believing that Ebola is a greater danger than it actually is. [ 189 ]


In Hazlehurst, Mississippi, in response to numerous parents keeping their children from attending school, a principal at Hazlehurst Middle School, agreed to take personal vacation time after he had traveled to Zambia, a country with no current Ebola cases and 3,000 miles (4,800 kilometres) away from West Africa. [ 190 ] [ 191 ]


The United States has the capacity to isolate and manage 11 patients in four specialized biocontainment units. These include the  University of Nebraska Medical Center  in Omaha, Nebraska, the  National Institutes of Health  in Bethesda, Maryland,  St. Patrick Hospital and Health Sciences Center  in Missoula, Montana and  Emory University Hospital  in Atlanta, Georgia. [ 120 ] [ 194 ] [ 195 ] [ 196 ]


There is as yet no medication for Ebola approved by the U.S.  Food and Drug Administration  (FDA). The director of the US  National Institute of Allergy and Infectious Diseases , Dr.  Anthony Fauci , has stated that the scientific community is still in the early stages of understanding how infection with the Ebola virus can be treated and prevented. [ 197 ]  There is no cure or specific treatment that is currently approved. [ 198 ]  However, survival is improved by early supportive care with rehydration and symptomatic treatment. Treatment is primarily  supportive  in nature. [ 199 ]  A number of experimental treatments are being considered for use in the context of this outbreak, and are currently or will soon undergo  clinical trials . [ 200 ] [ 201 ]


In late August 2014, both Kent Brantly and Nancy Writebol became the first people to be given the experimental drug  ZMapp . They both recovered, but there was no confirmation or proof that the drug was a factor. [ 202 ]  A Spanish priest with Ebola had taken ZMapp but died afterward. [ 203 ]  Up until that time, ZMapp had only been tested on primates and looked promising, causing no serious side effects and protecting the animals from infection. [ 204 ]  The  Bill & Melinda Gates Foundation  has donated $150,000 to help  Amgen  increase its production, and the U.S.  Department of Health and Human Services  has asked a number of centers to also increase production. [ 205 ]


There have been at least two promising treatments for those already infected. The first is  brincidofovir , an experimental antiviral drug, which was given to Duncan, Mukpo, and Spencer. [ 206 ]


Treatment using a transfusion of plasma from Ebola survivors, a form of "passive immunotherapy", [ 207 ]  since it contains  antibodies  able to fight the virus, has been used with apparent success on a number of patients. [ 204 ]  Survivor Kent Brantly donated his blood to Rick Sacra, Ashoka Mukpo and nurse Nina Pham. [ 208 ] [ 209 ]  The  World Health Organization  (WHO) has made it a priority to try the treatment, and has been telling affected countries how to do it. [ 210 ]


Many Ebola  vaccine  candidates had been developed in the decade before 2014, but none has yet been approved for clinical use in humans. [ 211 ]  Several promising vaccine candidates have been shown to protect nonhuman primates (usually macaques) against lethal infection, and some are now going through the  clinical trial  process. [ 212 ] [ 213 ]


In late October 2014, Canada planned to ship 800 vials of an experimental vaccine to the WHO in Geneva, the drug having been licensed by NewLink Genetics Corporation, of Iowa. British drugmaker  GlaxoSmithKline  also announced it had expedited research and development of a vaccine, which, if successful, could be available in 2015. [ 214 ]  Although it's still unknown which ones will be approved, WHO hopes to have millions of vaccine doses ready sometime in 2015, and expects that five more experimental vaccines will start being tested in March 2015. [ 215 ]


In December 2019, the first Ebola vaccine was approved. [ 216 ]   rVSV-ZEBOV , otherwise known as Ervebo, is a vaccine for adults that prevents the  Zaire ebolavirus . [ 217 ]


In October 2014,  Navarro College , a two-year public school located in Texas, received media attention for admission rejection letters sent to two prospective students from Nigeria. The letters informed the applicants that the college was "not accepting international students from countries with confirmed  Ebola  cases". [ 218 ]  On October 16, Navarro's Vice-President Dewayne Gragg issued a statement confirming that there had indeed been a decision to "postpone our recruitment in those nations that the Center for Disease Control and the U.S. State Department have identified as at risk". [ 219 ]  Nigeria's outbreak was among the least severe in West Africa and was considered over by the WHO on October 20; the Nigerian health ministry had previously announced on September 22 that there were no confirmed cases of Ebola within the country. [ citation needed ]


In October 2014, the  S. I. Newhouse School of Public Communications  at Syracuse University withdrew an invitation it had extended to  Pulitzer Prize  winning photojournalist  Michel du Cille  because he'd returned three weeks earlier from covering the  Ebola outbreak in Liberia . [ 220 ] [ 221 ]  In October 2014,  Case Western Reserve University  withdrew their speaking invitation to Dr.  Richard E. Besser , chief health editor at  ABC News  and former director of the CDC. Besser had recently returned from a trip to  Liberia . [ 221 ] [ 222 ] [ 223 ]


On October 17,  Harvard University  imposed limits on travel to Ebola-affected countries (Sierra Leone, Guinea and Liberia) for its students, staff, and faculty.  All travel to these countries is "strongly discourage[d]", and such travel as part of a Harvard program requires approval from the  provost . [ 224 ]


On October 25, CDC allowed state and local officials to set tighter control policies and Barbara Reynolds, a CDC spokeswoman released a statement saying "we will consider any measures that we believe have the potential to make the American people safer". [ 225 ]  On November 1, Ohio tightened restrictions on people travelling to Western African countries impacted by Ebola. [ 226 ] Time  magazine's 2014  Person of the Year  issue honored health professionals dedicated to fighting Ebola, including Kent Brantly. [ 227 ]


On October 28, future president  Donald Trump  tweeted that governors backing off from the Ebola quarantine would lead to more mayhem. [ 228 ]  In 2020, during the  COVID-19 pandemic in the United States , these tweets were contrasted with Trump's then-opposition to mandatory quarantines. [ 228 ]


Ebola virus disease in Mali  occurred in October 2014, [ 2 ]  leading to concern about the possibility of an outbreak of Ebola in Mali. A child was brought from Guinea and died in the northwestern city of  Kayes . [ 3 ]  Mali  contact traced  over 100 people who had contact with the child; tracing was completed in mid-November with no further cases discovered. [ 4 ]  In November, a second unrelated outbreak occurred in Mali's capital city,  Bamako . Several people at a clinic are thought to have been infected by a man traveling from Guinea. [ 5 ]   On January 18, Mali was declared Ebola-free after 42 days with no new cases. There had been a cumulative total of eight cases with six deaths. [ 1 ] [ 6 ]


As of late 2014,  the Ebola virus epidemic  in Mali's southern neighbors  Liberia ,  Sierra Leone , and  Guinea  has led to thousands of deaths. Mali, a country of about 16.5 million people, was ranked as one of the top four countries at risk for an outbreak prior to its first reported case. [ 7 ]


In late October 2014, a two-year-old girl died from Ebola in the city of  Kayes . [ 8 ]  The child, later identified as Fanta Kone, was admitted to hospital on 21 October, where she tested positive for  typhoid . Further tests confirmed Ebola. [ 9 ] [ 10 ]  The child, her grandmother,  uncle, and five-year-old sister [ 11 ]  arrived in  Bamako  after traveling roughly 1000 km (600 miles) from Guinea, where Kone's father had died. [ 8 ] [ 10 ]  They then traveled to Kayes by bus. [ 3 ] [ 12 ]


Fanta Kone's father, a  Red Cross  worker, assisted at a private medical clinic in  Beyla  that was owned and run by his father, Fanta's paternal grandfather. It is suspected that he may have contracted Ebola from a farmer from another village, who sought treatment at the clinic and was accompanied by his two daughters. The farmer died on 12 September, and his daughters on 23 September. After falling ill in late September, Fanta's father traveled to his native village of  Sokodougou , 70 kilometres away, where he died on 3 October. By 20 October, the paternal grandfather, his wife, and two sons had also died, with some deaths confirmed to have been from Ebola disease. Fanta's mother and 3-month-old sibling remain disease-free and are residing in Guinea during a 40-day mourning period before joining the rest of her family in Mali. [ 13 ]


The hospital  pediatrician  in Kayes said he was told that the child had been born and raised in Kayes, and that he was not informed of her journey from Guinea. [ 14 ]  The child's samples were tested at Mali's Center for TB and AIDS Research. [ 15 ]  Hemorrhagic fevers like Ebola,  Marburg virus , and  Lassa fever  can have similar symptoms, and testing can help determine if a person has a case of one of these diseases. [ 16 ]  There are about half a million cases of Lassa fever per year in West Africa, causing about 5,000 deaths. [ 17 ]


There was concern that Kone had exposed others to the virus during her journey because she had been bleeding from her nose. [ 18 ]  Contact with blood or feces from someone ill with Ebola is a high risk factor for the disease. [ 19 ]  By 25 October, it was estimated that the child  had contact  with as many as 300 people, 43 of whom were placed in  isolation  to prevent the disease from spreading. [ 20 ]  Of the 43, 10 were health care workers. [ 21 ]  By 27 October, 111 people had been identified as contacts, but the search was hampered by a lack of health care workers, [ 22 ]   and 40 volunteers were trained to help with the contact tracing. [ 23 ]  By 29 October it was thought she had contact with 141 people, however not all of them were found, including 6 of the 10 people on the bus ride with the child from the Guinea border to Bamako. [ 24 ]


By 5 November there were no known cases besides the child, although the risk of more cases was still considered to be high. [ 25 ]  108 people who had contact with the child were quarantined, although 40 contacts remained missing as of 9 November. [ 25 ]  Those being watched have their temperature taken twice daily. [ 14 ]  The Mali Ministry of Health hoped to release these 108 people from monitoring in mid-November, and all contacts successfully completed their 21-day waiting period on 15 November. [ 26 ]


On 12 November, Mali confirmed its second and third deaths from Ebola: an  imam  from Guinea, and a nurse who was treating him at a clinic in Mali's capital city  Bamako . The cases are unrelated to the earlier case in Kayes. [ 27 ]


A nurse in Bamako who had treated the imam subsequently fell ill; on 11 November he tested positive for Ebola and died on the same day. A second case was confirmed in a doctor who also worked at the clinic and treated the imam. He developed symptoms on 5 November and died on 20 November. [ 27 ] [ 28 ]


By 12 November, 90 contacts had been quarantined across the city of Bamako, including about 20 U.N. peacekeepers who were treated at the clinic for injuries sustained while on duty. The government placed both the clinic and the imam's mosque in full lock-down. Contact tracing has been hampered because the imam died two weeks prior to his diagnosis; he was not suspected of having Ebola until the nurse tested positive for the disease. He was buried with full traditional rites, including washing the body, and may have exposed many mourners to the virus. [ 29 ]


On 19 November, the WHO updated the status of cases in Mali. The imam was reclassified and not counted in Mali, but considered a Guinea case. The second case in Mali was that of the nurse who treated the imam, and the doctor who treated the imam was the third case. The next three cases were related to the imam as well: a man who had visited the imam while he was in hospital, his wife, and his son.  Ebola infection was laboratory-confirmed in the wife and the son. [ 30 ]  As of 15 November, a total of 407 possible contacts are being traced, according to an official health ministry report. [ 31 ]  On 18 November, the number of contacts was raised to 600 people that were being monitored. [ citation needed ]


On Monday 24 November, a government statement raised the number of cases in Mali to eight and six deaths. All the new cases are linked back to the imam. [ 32 ]  On 4 December, Mali received its first mobile lab, which can be sent to remote hotspots, if needed. [ 33 ] [ 34 ]  On 6 December, U.N. peacekeepers were released from quarantine at the Pasteur Clinic. [ 35 ]  On December 12, the last case in treatment recovered and was discharged, "so there are no more people sick with Ebola in Mali,” according to a Ministry of Health source. [ 36 ]  On December 16,  Mali released the final 13 individuals that were being quarantined, therefore the country will be declared free of the virus on January 18, according to WHO. "There is no more contact-tracing ... and there is no suspected case of Ebola," a spokesperson for WHO indicated. [ 1 ] [ 37 ]


In October, the Fousseyni Daou Hospital developed an Ebola management plan.  The Governor of Kayes closed all the schools in Kayes and urged all residents to strictly observe hygiene recommendations to help stop the spread of disease. [ 38 ]  The Mali ministry of health has joined with tribal leaders to launch an information campaign.  They also set up a telephone hotline for Ebola information. [ citation needed ] The phone line allows people to hear information, as the literacy rate in Mali is about 30-40 percent. [ 39 ]


As a result of the efforts to spread Ebola information, concern about the disease has resulted in some changes in traditional practices.  Some Malians have begun to change their burial rituals, to greet others by waving rather than shaking hands, and to avoid eating from the same dish, as is typically done throughout Africa.
 [ 40 ]


Earlier in the year, before the disease had broken out in Mali, a  biosafety level -3 laboratory was set up in Bamako to prepare for the possibility of an outbreak.  Previous to the ability to diagnose Ebola in Mali, samples needed to be sent out, taking three weeks for confirmation "while panic and rumor spread on the streets of the capital and frightened patients sat in quarantine."  With the installation of the new laboratory, samples can be processed in only a few hours. [ 41 ] [ 42 ]


On 25 October, the  United Nations Humanitarian Air Service  delivered a shipment of about one ton of medical supplies by air to help Mali. [ 43 ]  Doctors without Borders /  Medecins sans Frontieres  dispatched a team to Mali late October, to provide technical support to the Ministry of Health. [ 44 ]   The country shares an 800-kilometer border with Guinea which it continues to monitor. [ 45 ]


There is a dire need for health care assistance in Mali. In 2010, Mali was reported to have about 8 physicians per 100,000 inhabitants and one hospital bed per 10,000 inhabitants. [ 46 ]  Forty-five percent of the children are malnourished and one in four die before the age of five. [ 47 ]


Common diseases in Mali include  hepatitis A ,  malaria ,  yellow fever  and  typhoid .  Malaria, which kills about 700 thousand people a year in Africa, [ 48 ]  is caused by a one-celled parasite spread by mosquitos. [ 49 ]  Mali is part of the " meningitis  belt" in West Africa and the disease becomes more common in the dry season between December and June. [ 50 ]  Mali has also experienced outbreaks of  meningococcal meningitis . [ 51 ]   Tuberculosis , which is a bacterial disease (not a virus like Ebola), is also a leading cause of disease in Mali. [ 52 ]


Following the Ebola outbreak, many doctors and nurses that work at the Pasteur Clinic in Bamako are facing the stigma of Ebola, regardless of not having been in contact with any of the admitted Ebola patients. A nurse held out at her house for two days waiting for rescue, while "Several of our doctors' children don't go to school anymore" because "People insult them, close relatives are distant. Even spouses and husbands are panicking," per a comment from the director of the Pasteur Clinic, Dramane Maiga. [ 53 ]


As part of a clinical trial, 50 health workers in Mali received an experimental Ebola vaccine during October and November; these workers are involved in the investigation and control of the current outbreak. [ 54 ]  By 23 November, Mali reported 2 cases of Ebola infection among healthcare workers and 1 had died. [ 32 ] [ 55 ]


"Africa Stop Ebola" , featuring contributions from Malian, Guinean, Ivorian, Congolese and Senegalese artists, was recorded in several of the local languages to raise awareness of Ebola. [ 56 ] [ 57 ]


In 2014,  Ebola virus disease in Spain  occurred due to two patients with cases of the disease contracted during the  Ebola virus epidemic in West Africa ; they were  medically evacuated . [ 1 ] [ 2 ]  A failure in infection control in the treatment of the second patient led to an isolated infection of Ebola virus disease in a health worker in Spain itself. The health worker survived her Ebola infection, and has since been declared infection-free. [ 3 ]


On 5 August 2014, the  Brothers Hospitallers of St. John of God  confirmed that Brother  Miguel Pajares , who had been volunteering in Liberia, had become infected. He was evacuated to Spain on 6 August 2014, and subsequently died on 12 August. [ 1 ]  On 21 September it was announced that Brother Manuel García Viejo, another Spanish citizen who was medical director at the  St John of God Hospital Sierra Leone  in  Lunsar , had been evacuated to Spain from Sierra Leone after being infected with the virus. His death was announced on 25 September. [ 2 ]  Both of these cases were treated at the  Hospital Carlos III  in Madrid. [ 4 ]


In October 2014, María Teresa Romero Ramos, an  auxiliary nurse  who had cared for Manuel García Viejo [ 5 ]  at the Hospital Carlos III had become unwell and on 6 October tested positive for Ebola at her local hospital in  Alcorcón , the  Hospital Universitario Fundación Alcorcón . [ 6 ] [ 7 ] [ 8 ]  A second test confirmed the diagnosis, [ 9 ]  making this the first confirmed case of Ebola transmission outside Africa. Following testing, she was transferred to the  Hospital Carlos III  in Madrid for treatment. [ 10 ]


As of October 7, 50 contacts were being monitored, with 7 kept in isolation at the Hospital Carlos III, and an investigation was under way. [ 11 ] [ 12 ]


On 7 October, Madrid's regional government got a court order to euthanize Romero's pet dog, Excalibur, concerned that it posed a risk as a  reservoir host . [ 13 ]   By the afternoon there were over 30 animal rights activists who had barricaded the apartment to prevent officials from removing the dog.  A number of online petitions were started rallying to save the dog, garnering hundreds of thousands of indications of support.  Ramos' quarantined husband, Javier, called on a veterinarian radio show host, and recorded a video appeal, for help to save his dog.  On 8 October, Spanish authorities removed, sedated and euthanized the dog and arranged for the safe disposal of its remains. [ 14 ]


On 9 October the Spanish health ministry quarantined three more people. [ 8 ]
The health authorities announced that María Teresa Romero Ramos' condition had worsened significantly. [ 15 ]  On October 12, she began to show some improvement.
According to one report, the improvement may be attributed to Romero's having received the experimental drug  ZMab  which is similar to  ZMapp , which has been used to treat several Ebola patients.   However, according to information released by Spain's Centre for Health and Emergency Alerts, the nurse did not receive ZMab due to concerns over possible side-effects. [ 16 ] [ 17 ]  Romero, however, was given the experimental antiviral drug  Favipiravir , and it was reported that the dosages used were much higher than those used in the treatment of other patients. [ 18 ]


Medical staff in Madrid protested about the lack of effective protective equipment and safety precautions. [ 15 ]  It was reported on October 17 that all the other people suspected of being infected in Spain had tested negative for the Ebola virus. [ 19 ]


On October 20 it was announced that Teresa Romero had tested negative for the Ebola virus, [ 3 ]  suggesting she may have cleared the virus from her system. On November 1, it was announced that she was Ebola-free, and had been moved out of the isolation ward into a normal hospital bed to finish the process of recuperation from her illness. [ 20 ]  The WHO declared Spain Ebola-free on 2 December, 42 days after Teresa Romero was shown to be free of Ebola on 21 October. [ 21 ]


In July 2018, a Spanish team from the  October 12 Hospital  in  Madrid  announced the discovery of an  antibody  and the development of a prototype vaccine against five strains of Ebola, including the most common and deadliest. [ 22 ] [ 23 ] [ 24 ]


The Ebola cases in Spain occurred when the country was governed by the  People's Party , under prime minister  Mariano Rajoy . The opposition  Spanish Socialist Workers' Party  (PSOE) used its official Twitter account to directly blame Rajoy for the outbreak, and party leader  Pedro Sánchez  called the government a "disgovernment" while calling for the dismissal of Health Minister  Ana Mato .  Pablo Iglesias , leader of the left-wing party  Podemos  also blamed the government for the outbreak. These comments received scrutiny during the  COVID-19 pandemic in Spain  in which tens of thousands of people were infected and thousands died, while Sánchez was prime minister and Iglesias deputy prime minister. [ 25 ] [ 26 ] [ 27 ] [ 28 ]


Favipiravir , sold under the brand name  Avigan  among others, [ 3 ]  is an  antiviral medication  used to treat  influenza  in Japan. [ 4 ]  It is also being studied to treat a number of other viral infections, including  SARS-CoV-2 . [ 4 ]  Like the experimental antiviral drugs T-1105 and T-1106, it is a  pyrazinecarboxamide  derivative. [ 5 ]


It is being developed and manufactured by  Toyama Chemical  (a subsidiary of  Fujifilm ) and was approved for medical use in Japan in 2014. [ 6 ]  In 2016, Fujifilm licensed it to  Zhejiang Hisun Pharmaceutical Co. [ 7 ]  It became a  generic drug  in 2019. [ citation needed ]


Favipiravir has been approved to treat  influenza  in Japan. [ 6 ]  It is, however, only indicated for novel influenza (strains that cause more severe disease) rather than  seasonal influenza . [ 6 ] [ 8 ]  As of 2020, the probability of resistance developing appears low. [ 6 ]


There is evidence that use during pregnancy may result in  harm to the baby . [ 6 ]  Teratogenic and embryotoxic effects were shown on four animal species. [ 6 ] [ 9 ]  In one case report, a 6-month old infant developed benign bright blue discolouration of the cornea after treatment with favipiravir which resolved after treatment cessation. [ 10 ]


The mechanism of its actions is thought to be related to the selective inhibition of viral  RNA-dependent RNA polymerase . [ 11 ] [ medical citation needed ]  Favipiravir is a  prodrug  that is metabolized to its active form, favipiravir-ribofuranosyl-5'-triphosphate (favipiravir-RTP), available in both oral and intravenous formulations. [ 12 ] [ 13 ]  In 2014, favipiravir was approved in Japan for stockpiling against  influenza pandemics . [ 14 ]  However, favipiravir has not been shown to be effective in primary human airway cells, casting doubt on its efficacy in influenza treatment. [ 15 ]


Favipiravir-RTP is a  nucleoside analogue . It mimics both guanosine and adenosine for the viral RdRP. Incorporating two such bases in a row stops primer extension, although it is unclear how as of 2013. [ 11 ]


There are multiple pathways to synthesize favipiravir. [ 16 ] [ 17 ]  One synthesis starts with  3-Hydroxypicolinic acid , [ 18 ]  which is first reacted with  thionyl chloride  and then aqueous  ammonia  to produce 3-Hydroxypyrazine-2-carboxamide. The resulting material is nitrated with  potassium nitrate  and  sulfuric acid  to add a  nitro group  in the 6 position, which is then reduced using  hydrazine  hydrate to the corresponding amine. Finally, the amine is turned into a  diazonium group  using  sodium nitrite  and replaced with a fluorine group using  hydrofluoric acid .


The US Department of Defense developed favipiravir in partnership with MediVector, Inc. as a broad-spectrum antiviral and sponsored it through FDA Phase II and Phase III clinical trials, where it demonstrated safety in humans and efficacy against the influenza virus. [ 19 ]  favipiravir remains unapproved in the UK and the USA. [ 20 ]  In 2014, Japan approved favipiravir for treating influenza strains unresponsive to current antivirals. [ 21 ]  Toyama Chemical initially hoped that favipiravir would become a new influenza medication that could replace  oseltamivir  (brand name Tamiflu). However, animal experiments show the potential for  teratogenic  effects, and the approval of production by The Ministry of Health, Labor and Welfare was greatly delayed and the production condition is limited only in an emergency in Japan. [ 22 ]


Despite limited data on efficacy, as of March 2021 favipiravir is widely prescribed for outpatient treatment of mild to moderate COVID-19 in Egypt, [ 23 ]  Hungary [ 24 ]  and Serbia. [ 25 ]  Patients are required to sign a consent form before obtaining the drug. [ citation needed ]


Favipiravir is sold under the brand names Avigan  ( アビガン ,  Abigan ) , Avifavir, [ 1 ]  Avipiravir, [ 26 ]  Areplivir, [ 2 ]  FabiFlu, [ 27 ]  Favipira, [ 28 ]  Reeqonus, [ 29 ] [ 30 ]  and Qifenda.


Coronavir is the brand name of favipiravir used in  Russia , where it is  approved for the treatment of  COVID-19 . It is produced and sold by  R-Pharm . [ 31 ] [ 32 ]  Coronavir was approved for use in Russia in hospitals in July 2020, and in September 2020 it received approval for prescription sales for outpatient use. [ 33 ]


Favipiravir, as an antiviral drug, has been authorized for treating COVID-19 in several countries including Japan, Russia, Serbia, Turkey, India, and Thailand, under emergency provisions. [ 34 ] [ 35 ] [ 36 ] [ 37 ]  A rapid meta-review in September 2020 (analyzing four studies) noted that the drug led to clinical and radiological improvements; however, no reduction in mortality or differences in oxygen-support requirement were observed and more rigorous studies were sought. [ 38 ] [ 39 ]  A Cochrane Systematic review published in Feb 2024, noted that there is actually no real benefit with Favipiravir in treating Covid-19 in terms of mortality benefits, or admission to mechanical ventillation, or hospitalisation, and it may not make any difference in adverse effects or serious adverse effects. [ 40 ]


As of May 2021 [update] , large-cohort clinical trials are underway. [ 41 ]


Research in 2014, suggested that favipiravir may have efficacy against  Ebola  based on studies in  mouse models ; efficacy in humans was unaddressed. [ 42 ] [ 43 ] [ 44 ]


During the  2014 West Africa Ebola virus outbreak , a French nurse who contracted Ebola while volunteering for  Médecins Sans Frontières  (MSF) in Liberia reportedly recovered after receiving a course of favipiravir. [ 45 ]  A clinical trial investigating the use of favipiravir against Ebola virus disease began in  Guéckédou , Guinea, in December 2014. [ 46 ]  Preliminary results presented in 2016 at the  Conference on Retroviruses and Opportunistic Infections  (CROI), later published, showed a decrease in mortality in patients with low-to-moderate levels of virus in blood, but no effect on patients with high levels (the group at a higher risk of death). [ 47 ] [ 48 ] [ 49 ]  The trial design was concomitantly criticised for using only historical controls. [ 50 ]


Nipah virus  is a causative agent of outbreaks of encephalitis with pneumonia and has a high  case fatality rate . The first outbreak occurred in Malaysia-Singapore, related to contact with pigs in slaughterhouses and an outbreak in Philippines related to slaughter of horses, most other outbreaks have affected India and Bangladesh. in Bangladesh outbreaks are often associated with consumption of raw date palm sap contaminated by saliva and urine of fruit bats. [ 51 ]  In a study published in the Scientific Reports, Syrian hamster model for Nipah virus infection was used, which closely mirrors most aspects of human disease, such as widespread vasculitis, pneumonia, and encephalitis. The hamsters were infected with a lethal dose of 10 4  PFU NiV-M via the intraperitoneal (i.p.) route similar to previous studies and treatment was initiated immediately after infection. Favipiravir was administered twice daily via the peroral (p.o.) route for 14 days. The treated hamsters displayed 100% survival and no obvious morbidity after lethal NiV challenge, whereas all the control cases died of severe disease. [ 52 ]


In experiments in animals favipiravir has shown activity against  West Nile virus ,  yellow fever virus ,  foot-and-mouth disease virus  as well as other  flaviviruses ,  arenaviruses ,  bunyaviruses  and  alphaviruses . [ 53 ]  Activity against  enteroviruses [ 54 ]  and  Rift Valley fever  virus has also been demonstrated. [ 55 ]  Favipiravir has showed limited efficacy against  Zika virus  in animal studies, but was less effective than other antivirals such as  MK-608 . [ 56 ]  The agent has also shown some efficacy against  rabies , [ 57 ]  and has been used experimentally in some humans infected with the virus. [ 58 ]


The possible  tautomerism  of favipiravir has been investigated computationally [ 59 ]  and experimentally. [ 60 ]  It was found that the enol-like form was substantially more stable in organic solvents than the keto-like form, meaning that Favipiravir likely exists almost exclusively in the enol-like form. In aqueous solution the keto-like tautomer is substantially stabilized due to the specific interaction with the water molecules. Upon protonation the keto form is switched on. [ citation needed ]


FGI-103  is an  antiviral drug  developed as a potential treatment for the  filoviruses   Ebola virus  and  Marburg virus . In tests on mice FGI-103 was effective against both Ebola and Marburg viruses when administered up to 48 hours after infection. The mechanism of action of FGI-103 has however not yet been established, as it was found not to be acting by any of the known mechanisms used by similar antiviral drugs. [ 1 ] [ 2 ] [ 3 ]


FGI-104  is the name of an experimental broad-spectrum  antiviral drug , with activity against a range of viruses including  hepatitis B ,  hepatitis C ,  HIV ,  Ebola virus , and  Venezuelan equine encephalitis virus .  [ 1 ]


The drug acts by inhibiting the protein  TSG101 , which transports newly manufactured virions to the exterior of an infected cell, thus breaking the replication cycle of the virus. In pre-clinical studies, FGI-104 has been shown to protect mice from  Ebola virus disease . [ 2 ] [ 3 ]


FGI-106  is a broad-spectrum  antiviral drug  developed as a potential treatment for enveloped RNA viruses, in particular  viral hemorrhagic fevers  from the  bunyavirus ,  flavivirus  and  filovirus  families. It acts as an inhibitor which blocks viral entry into host cells. In animal tests FGI-106 shows both prophylactic and curative action against a range of deadly viruses for which few existing treatments are available, including the bunyaviruses  hantavirus ,  Rift Valley fever virus  and  Crimean-Congo hemorrhagic fever virus , the flavivirus  dengue virus , and the filoviruses  Ebola virus  and  Marburg virus . [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]


Galidesivir  ( BCX4430 ,  immucillin-A ) is an  antiviral drug , an  adenosine analog [ 1 ]  (a type of  nucleoside analog ). [ 2 ]  It was developed by  BioCryst Pharmaceuticals  with funding from  NIAID , originally intended as a treatment for  hepatitis C , but subsequently developed as a potential treatment for deadly  filovirus  infections such as  Ebola virus disease  and  Marburg virus disease , as well as  Zika virus . [ 3 ]  Currently, galidesivir is under  phase 1 human trial  in Brazil for  coronavirus . [ 4 ]


It also shows  broad-spectrum antiviral  effectiveness against a range of other RNA virus families, including  bunyaviruses ,  arenaviruses ,  paramyxoviruses ,  coronaviruses ,  flaviviruses , and  phleboviruses . [ 5 ]  Galidesivir has been demonstrated to protect against both Ebola and Marburg viruses in both rodents and monkeys, even when administered up to 48 hours after infection, [ 1 ]  and development for use in humans was then being fast-tracked due to concerns about the lack of treatment options for the 2013-2016  Ebola virus epidemic in West Africa . [ 6 ]


Galidesivir later showed efficacy against  Zika virus  in a mouse model. [ 7 ]


Galidesivir abrogates viremia in Zika virus–infected rhesus Macaques. [ 8 ]


Galidesivir is one of several antiviral drugs being tested for  coronavirus disease 2019 . [ 9 ]


On April 9, 2020, BioCryst opened enrollment into a randomized, double-blind,  placebo -controlled clinical trial to assess the safety, clinical impact and antiviral effects of galidesivir in patients with  COVID-19 . [ 4 ]


GamEvac-Combi  (Russian:  ГамЭвак-Комби ) is a heterologous VSV- and Ad5-vectored  Ebola vaccine . There is also a version called  GamEvac  which is a homologous Ad5-vectored vaccine. [ 1 ]  GamEvac-Combi was developed by  Gamaleya Research Institute of Epidemiology and Microbiology . As of 2015 [update]  the vaccine has been licensed in Russia for emergency use, on the basis of Phase 1 and Phase 2 clinical trials. [ 2 ]


The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. [ 3 ]  The vaccine is targeted against the Makona variant of Ebola that was circulating in West Africa during the 2013-2016 outbreak. [ 4 ]


GamEvac-Combi was licensed by the  Ministry of Health of the Russian Federation  for emergency use in the territory of the Russian Federation in December 2015. The emergency license was based on Phase I and II clinical data of safety and immunogenicity. [ 2 ]


JK-05  is a broad-spectrum  antiviral drug  developed by the  Chinese  company Sihuan Pharmaceutical along with the  Chinese Academy of Military Medical Sciences . It is reported to act as an inhibitor of the viral enzyme  RNA polymerase , which is essential for viral replication. In tests on mice, JK-05 was claimed to show efficacy against a range of  RNA viruses , including  influenza ,  Ebola virus , and  yellow fever , as well as several  arenaviruses  and  bunyaviruses . The  chemical structure  of JK-05 has not been disclosed as of October 2014, but it is claimed to be a  small molecule  drug with a comparatively simple structure, which should be readily amenable to synthesis scale-up for mass production if testing is successful. The drug is, however, admitted to be similar to the Japanese anti-influenza drug  favipiravir , developed by  Fujifilm  Holdings Corp, which has been used effectively to treat patients with Ebola. [ 1 ]  In addition, WHO committee members mentioned that the drug is a copy product of favipiravir, because patents of favipiravir were already registered in 2006 in China. [ 2 ]  The drug has been given preliminary approval by the Chinese authorities to be available for Chinese health workers involved in combating the  2014 West African Ebola outbreak , or if Ebola were to spread into mainland China. [ 3 ] [ 1 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ]  Several other Chinese developed antiviral drugs with anti-Ebola activity have also been disclosed, [ 8 ]  but have not progressed so far through development as JK-05. [ citation needed ]


Maftivimab  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 ]


Monitored Emergency Use of Unregistered and Investigational Interventions  ( MEURI ) is an  ethical protocol  developed by the  World Health Organization  to evaluate the potential use of experimental drugs in the event of  public health emergencies . [ 1 ] [ 2 ]
The protocol was created by the  WHO Ebola Ethics Working Group  in 2014 [ 3 ] [ 4 ]  in the context of the  2014 West Africa Ebola outbreak . The WHO recommends that the term be preferred to the term " compassionate use " or " expanded access " for the controlled use of unregistered treatments in public health emergency measures. [ 5 ] [ 6 ]


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


Odesivimab  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 ]


Post-Ebola virus syndrome  (or  post-Ebola syndrome ) is a  post-viral syndrome  affecting those who have recovered from infection with  Ebola . [ 3 ]   Symptoms include joint and muscle pain, eye problems, including blindness, various neurological problems, and other ailments, sometimes so severe that the person is unable to work. [ 4 ]   Although similar symptoms had been reported following previous outbreaks in the last 20 years, health professionals began using the term in 2014 when referring to a constellation of symptoms seen in people who had  recovered from an acute attack of Ebola disease. [ 5 ]


Researchers have been aware of a group of symptoms that frequently followed  Ebola virus disease  for 20 years, but it became more widely reported with the large number of survivors of the  deadly epidemic in West Africa  in 2014. [ 3 ] [ 6 ] [ 7 ] [ 8 ] [ 2 ]
Post Ebola syndrome may manifest as  joint pain ,  muscle pain ,  chest pain ,  fatigue ,  hearing loss ,  hair loss ,  cessation of menstruation , and poor long-term health. Some survivors report neurological issues including memory problems and  anxiety attacks .  Vision loss  is also frequently reported, along with eye pain,  inflammation , and blurred vision. [ 1 ]  Two papers published in the  New England Journal of Medicine  in 2015 report that symptoms include lethargy, joint pains, hair loss, and  vision loss, frequently to the point of near blindness, and  uveitis . [ 9 ] [ 10 ]


Although, there is some progress that may potentially help Ebola survivors, adequate funding and further research is required to help provide more answers about post-Ebola syndrome. [ 11 ]


Studies from previous outbreaks reveal that the virus is able to survive for months after recovery in some parts of the body such as the eyes and testes, where the  immune system  cannot reach.   It is not known if the neurologic symptoms seen in survivors are a direct result of the virus or, instead, triggered by the immune system's response to the infection.  It is known that Ebola can trigger a massive  cytokine storm  that can cause bleeding throughout the body, including the brain, which may explain various neurological symptoms that have been reported. [ 12 ]


In terms of diagnosis, the individual may show sensitivity to light or eye redness when ocular problems are suspected. Neurologically the individual's coordination,  gait  and  frontal release signs  should be observed. [ 2 ]


Management depends on the symptoms displayed, for example, if the individual indicates muscular-skeletal pain then  paracetamol  may be administered. If the individual presents with ocular problems, then  prednisone  and  cyclopentolate  may be used for treatment, according to the WHO. [ 2 ]


According to a review by Brainard, et al., Ebola virus was identified in almost 3 out of 4  seminal fluid  samples (18 survivors) almost 4 months after initial infection, with the last positive samples being more than 6 months (203 days) after infection had occurred. [ 13 ]  Another aspect of survivors of the Ebola virus, is that it could become sexually transmitted, as the virus is present in semen nine months after the individuals are declared free of Ebola. [ 14 ]  A 2017 study found the virus in the semen of some men after more than two years following the recovery from the acute infection [ 15 ]  and in one case, Ebola viral RNA was identified up to 40 months after illness. [ 16 ]


At the start of 2021 an outbreak of EVD that caused 18 cases and 9 deaths in Guinea is thought to be due to a West Africa Ebola outbreak survivor. This individual apparently infected a woman more than 5 years after he himself had incurred the infection [ 17 ]


An observational study, done roughly 29 months after the 2007  Bundibugyo  outbreak in  Uganda , found that long-term  sequelae  (i.e. consequences) persisted among survivors. Symptoms included eye pain, blurred vision, hearing loss, difficulty swallowing, difficulty sleeping, arthralgias, memory loss or confusion, and "various constitutional symptoms controlling for age and sex". [ 18 ]


From August through December 2014, a total of 10 patients with Ebola were treated in US hospitals; of these patients, 8 survived. In March 2015, the CDC interviewed the survivors; they all reported having had at least one adverse symptom during their recovery period. The symptoms ranged from mild (e.g. hair loss) to more severe complications requiring re-hospitalisation or treatment. The most frequently reported symptoms were lethargy or fatigue, joint pain, and hair loss. Sixty-three per cent reported having eye problems including two who were diagnosed with uveitis, 75% reported psychological or cognitive symptoms, and 38% reported neural difficulties. Although most symptoms resolved or improved over time, only one survivor reported complete resolution of all symptoms. [ 19 ]


A study published in May 2015 discussed the case of Ian Crozier, a Zimbabwe-born physician and American citizen who became infected with Ebola while he was working at an Ebola treatment centre in Sierra Leone. He was transported to the US and successfully treated at Emory University Hospital. However, after discharge Crozier began to experience symptoms including low back pain, bilateral  enthesitis  of the  Achilles tendon ,  paresthesias  involving his lower legs, and eye pain, which was diagnosed as uveitis. His eye condition worsened and a specimen of  aqueous humor  obtained from his eye tested positive for Ebola. The authors of the study concluded that "further studies to investigate the mechanisms responsible for the ocular persistence of Ebola and the possible presence of the virus in other  immune-privileged  sites (e.g., in the  central nervous system ,  gonads , and  articular cartilage ) are warranted." The authors also noted that 40% of participants in a survey of 85 Ebola survivors in Sierra Leone reported having "eye problems", though the incidence of actual uveitis was unknown. [ 20 ]


Another study, which was released in August 2015 looked at the health difficulties reported by survivors. Calling the set of symptoms "post-Ebolavirus disease syndrome", the research found symptoms that included "chronic joint and muscle pain, fatigue, anorexia, hearing loss, blurred vision, headache, sleep disturbances, low mood and short-term memory problems", and suggested the "implementation of specialised health services to treat and follow-up survivors". [ 21 ]


Researchers from the  National Institute of Neurological Disorders and Stroke  (NINDS) and Liberian research partners are doing a 5-year follow-up study of 1500 Ebola survivors in Liberia.  Survivors will be evaluated every 6 months; as of October 2017, two follow-ups have been performed.  Researchers will track relapses and viral persistence, characterize   sequelae  in various bodily systems, and do clinical studies on pharmacologic interventions and vaccines. [ 22 ]


PREVAIL III (Partnership for Research on Ebola Vaccines in Liberia III), a study of survivors and their contacts, a collaboration between NIAID and Liberia, was planned in late 2014. [ 23 ]  Early results described abdominal, chest, neurologic, musculoskeletal, and ocular [ 24 ]  challenges faced by survivors. [ 16 ]


PREVAIL IV examined if a medication, GS-5734, could help men with persistent Ebola virus RNA in semen to eliminate it, [ 25 ]  and thereby reduce the potential risk for sexual transmission.


PREVAIL VII examined if survivors of Ebola virus disease had evidence of Ebola virus RNA in aqueous humor and outcomes of cataract surgery relative to the local population. [ 26 ]


In 2018, over two years after the resolution of the Ebola outbreak in Eastern Sierra Leone, a study was conducted of Ebola survivors, with their families used as a control group.  The study was published in 2021, Looking at the results, the researchers were able to find an underlying process leading to persistent symptoms in some but not all Ebola survivors.  One hypothesis suggests "ongoing inflammation due to persistent infection vs autoimmune phenomena."  The authors suggest that more study is needed to come to conclusions about why some survivors continue to experience post syndrome ailments. [ 27 ]


There is a cure for the  Ebola virus disease  that is currently approved for market the US government has inventory in the Strategic National Stockpile. [ 1 ]  For past and current Ebola epidemics, treatment has been primarily  supportive  in nature. [ 2 ]


As of August 2023 [update] , treatment known as  atoltivimab/maftivimab/odesivimab  and experimental  ansuvimab  were found to be 90% effective. [ 3 ] [ 4 ] [ 5 ] [ 6 ]


In October 2020, the U.S.  Food and Drug Administration  (FDA) approved atoltivimab/maftivimab/odesivimab with an  indication  for the treatment of infection caused by  Zaire ebolavirus . [ 7 ]


In March 2014, the  World Health Organization  (WHO) reported  a major Ebola outbreak  in  Guinea , a western African nation. [ 8 ]  The disease then rapidly spread to the neighboring countries of  Liberia  and  Sierra Leone . The  2014 West African Ebola outbreak  is the largest Ebola outbreak ever documented, and the first recorded in the region. [ 8 ]


The director of the US  National Institute of Allergy and Infectious Diseases  (NIAID) has stated that the scientific community is still in the early stages of understanding how infection with the Ebola virus can be treated and prevented. [ 9 ]
The unavailability of treatments in the most-affected regions has spurred controversy, with some calling for experimental drugs to be made more widely available in Africa on a humanitarian basis, and others warning that making unproven drugs widely available would be unethical, especially in light of past experimentation conducted in developing countries by Western drug companies. [ 10 ] [ 11 ]  As a result of the controversy, on 12 August an expert panel of the WHO endorsed the use of interventions with as-yet-unknown effects for both treatment and prevention of Ebola, and also said that deciding which treatments should be used and how to distribute them equitably were matters that needed further discussion. [ 12 ]


Conventional trials to study efficacy by exposure of humans to the pathogen are obviously not feasible in this case. For such situations, the  Food and Drug Administration  (FDA) has established the " animal efficacy rule " allowing limited licensure to be approved on the basis of animal model studies that replicate human disease, combined with evidence of safety. A number of experimental treatments are being considered for use in the context of this outbreak, and are currently or will soon undergo  clinical trials . [ 13 ]  A  distributed computing  project,  Outsmart Ebola Together , has been launched by  World Community Grid  in collaboration with the  Scripps Research Institute  to help find chemical compounds to fight the disease. It uses the idle processing capacity of volunteers' computers and tablets. [ 14 ]


The centre for epidemic and microbiological research and treatment was constructed in the Guinean  Kindia  province. The centre was designed and created by  RUSAL  specialists with the assistance of  Rospotrebnadzor  scientists (RUSAL has invested $10 million). [ 15 ]


The  World Health Organization  (WHO) has stated that transfusion of whole blood or purified  serum  from Ebola survivors has the greatest potential to be implemented immediately, and has issued an interim guideline for this therapy. [ 50 ]  A study in Sierra Leone started in November 2014, and preliminary results show an 80 percent survival rate. [ 51 ]  Trials in Liberia and Guinea started in January 2015, with funding from the  Gates Foundation . [ 52 ]  Blood transfusions were also used in a 1995 outbreak in the Democratic Republic of the Congo, and 7 out of 8 patients survived. [ 53 ]


Ribavirin  is also known to be ineffective against ebolaviruses despite its effectiveness against other viral hemorrhagic fevers such as  Lassa fever . [ 54 ]
 Interferon therapies  have been tried as a form of treatment for EVD, but were found to be ineffective. [ 55 ]


One issue which hinders control of Ebola is that diagnostic tests that are 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. In December, a conference in Geneva will aim to work out which diagnostic tools could identify Ebola reliably and more quickly. The meeting, convened by the WHO and the non-profit  Foundation for Innovative New Diagnostics , seeks to identify tests that can be used by untrained staff, do not require electricity or can run on batteries or solar power and use reagents that can withstand temperatures of 40 °C (104 °F). [ 56 ]


As of February  2015 [update] , a number of diagnostic tests are under trial:


The  Hemopurifier  is a single-use disposable biological cartridge designed for use with dialysis machines and other blood circulatory pumps.  It is a method for removal of viruses from blood by  lectin  affinity hemodialysis which embodies reducing viral loads in the blood of individuals infected with a virus. [ 62 ]   During October 2014, the Hemopurifier was used as an adjunct in the treatment of a patient with  Ebola , who then recovered. [ 63 ]  The  FDA  subsequently approved the device for testing in up to 20 infected Ebola cases in the United States. [ 64 ]


Recombinant vesicular stomatitis virus–Zaire Ebola virus  ( rVSV-ZEBOV ), also known as  Ebola Zaire vaccine live  and sold under the brand name  Ervebo , is an  Ebola vaccine  for adults that prevents  Ebola  caused by the  Zaire ebolavirus . [ 4 ] [ 5 ] [ 6 ] [ 7 ]  When used in  ring vaccination , rVSV-ZEBOV has shown a high level of protection. [ 8 ] [ 9 ] [ 10 ]  Around half the people given the vaccine have mild to moderate adverse effects that include headache, fatigue, and muscle pain. [ 8 ]


rVSV-ZEBOV is a  recombinant , replication-competent  viral vector vaccine . [ 11 ]  It consists of rice-derived recombinant human serum albumin and live attenuated recombinant  vesicular stomatitis virus  (VSV), which has been genetically engineered to express the main  glycoprotein  from the  Zaire ebolavirus  so as to provoke a neutralizing  immune response  to the Ebola virus. [ 4 ] [ 12 ]


The vaccine was approved for medical use in the European Union and the United States in 2019. [ 5 ] [ 13 ] [ 12 ] [ 14 ]  It was created by scientists at the  National Microbiology Laboratory  in  Winnipeg, Manitoba , Canada, which is part of the  Public Health Agency of Canada  (PHAC). [ 15 ] [ 16 ]  PHAC licensed it to a small company, Newlink Genetics, which started  developing  the vaccine; Newlink in turn licensed it to  Merck  in 2014. [ 17 ]  It was used in the  DR Congo  in a  2018 outbreak in Équateur province , [ 18 ]  and has since been used extensively in the  2018–20 Kivu Ebola outbreak , with over 90,000 people vaccinated. [ 10 ]


Nearly 800 people were ring vaccinated on an emergency basis with VSV-EBOV when another Ebola outbreak occurred in Guinea in March 2016. [ 19 ]  In 2017, in the face of a  new outbreak of Ebola in the Democratic Republic of the Congo , the Ministry of Health approved the vaccine's emergency use, [ 20 ] [ 21 ]  but it was not immediately deployed. [ 22 ]


In April 2019, following a large-scale ring-vaccination scheme in the DRC outbreak, the WHO published the preliminary results of its research, in association with the DRC's  Institut National pour la Recherche Biomedicale , into the effectiveness of the ring vaccination program, stating that the  rVSV-ZEBOV-GP  vaccine had been 97.5% effective at stopping Ebola transmission, relative to no vaccination. [ 9 ] [ 10 ]


Systemic side effects include headache, feverishness, fatigue, joint and muscle pain, nausea, arthritis, rash, and abnormal sweating. [ 8 ] [ 23 ] [ 24 ] [ 4 ]
Injection-site side events include injection-site pain, swelling, and redness. [ 4 ]


rVSV-ZEBOV is a live, attenuated  recombinant   vesicular stomatitis virus  (VSV) in which the gene for the native envelope  glycoprotein  ( P03522 ) is replaced with that from the  Ebola virus  ( P87666 ),  Kikwit  1995 Zaire strain. [ 23 ] [ 25 ] [ 26 ]  Manufacturing of the vaccine for the Phase I trial was done by IDT Biologika. [ 27 ] [ 28 ]  Manufacturing of vaccine for the Phase III trial was done by  Merck , using the  Vero cell line , which Merck already used to make its  RotaTeq  vaccine against  rotavirus . [ 29 ] [ 30 ]


Scientists working for the  Public Health Agency of Canada  (PHAC) created the vaccine, and PHAC applied for a patent in 2003. [ 15 ] [ 16 ] [ 31 ]  From 2005, to 2009, three animal trials on the virus were published, all of them funded by the Canadian and U.S. governments. [ 28 ]  In 2005, a single intramuscular injection of the EBOV or MARV vaccine was found to induce completely protective immune responses in nonhuman primates ( crab-eating macaques ) against corresponding infections with the otherwise typically lethal EBOV or MARV. [ 32 ] [ 16 ]


In 2010, PHAC licensed the intellectual property on the vaccine to a small U.S. company called Bioprotection Systems, which was a subsidiary of Newlink Genetics, for US $205,000 and "low single-digit percentage" royalties. [ 33 ]  Newlink had funding from the U.S.  Defense Threat Reduction Agency  to develop vaccines. [ 15 ] [ 34 ] [ 35 ]


In December 2013, the  largest-ever Ebola epidemic  started in West Africa, specifically, in Guinea. [ 36 ]  On August 12, the WHO ruled that offering people infected with Ebola the RVSV-ZEBOV vaccine (which at the time was untested on humans) was ethical, and the Canadian government donated 500 doses of the vaccine to the WHO. [ 37 ] [ 38 ]  In October 2014, Newlink had no vaccine in production and no human trials underway, and there were calls for the Canadian government to cancel the contract. [ 33 ]  In September or October 2014, Newlink formed a steering committee among the interested parties, including PHAC, the NIH, and the WHO, to plan the clinical development of the vaccine. [ 39 ] [ 40 ]


In October 2014, Newlink Genetics began a Phase I clinical trial of rVSV-ZEBOV on healthy human subjects to evaluate the immune response, identify any side effects and determine the appropriate dosage. [ 34 ] [ 41 ] [ 42 ]  Phase I trials took place in Gabon, Kenya, Germany, Switzerland, the US, and Canada. [ 43 ] [ 44 ]  In November 2014, Newlink exclusively licensed rights to the vaccine to  Merck [ 17 ]  for US $50 million plus royalties. [ 45 ]


The Phase I study started with a high dose which caused  arthritis  and  skin reactions  in some people, and the vaccine was found replicating in the  synovial fluid  of the joints of the affected people; the clinical trial was halted because of that, then recommenced with a lower dose. [ 46 ]


In March 2015, a Phase II clinical trial and a Phase III started in Guinea at the same time; the Phase II trial focused on frontline health workers, while the Phase III trial was a  ring vaccination  in which close contacts of people who had contracted Ebola virus were vaccinated with VSV-EBOV. [ 47 ] [ 48 ]


In January 2016, the  GAVI Alliance  signed an agreement with Merck under which Merck agreed to provide VSV-EBOV vaccine for future outbreaks of Ebola and GAVI paid Merck  US$5 million ; Merck will use the funds to complete clinical trials and obtain regulatory approval. As of that date, Merck had submitted an application to the  World Health Organization  (WHO) through their Emergency Use Assessment and Listing (EUAL) program to allow for use of the vaccine in the case of another epidemic. [ 49 ]  It was used on an emergency basis in Guinea in March 2016. [ 19 ]


Results of the Phase III Guinea trial were published in December 2016. It was widely reported in the media that vaccine was safe and appeared to be nearly 100% effective, [ 50 ] [ 51 ]  but the vaccine remained unavailable for commercial use as of December 2016. [ 52 ]


In April 2017, scientists from the U.S.  National Academy of Medicine  (NAM) published a review of the response to the Ebola outbreak that included a discussion of how clinical trial candidates were selected, how trials were designed and conducted, and reviewed the data resulting from the trials.  The committee found that data from the Phase III Guinea trial were difficult to interpret for several reasons.  The trial had no placebo arm; it was omitted for ethical reasons and everyone involved, including the committee, agreed with the decision.  This left only a delayed treatment group to serve as a control, but this group was eliminated after an interim analysis showed high levels of protection, which left the trial even more  underpowered .  The committee found that under an  intention-to-treat analysis , the rVSV-ZEBOV vaccine might have had no efficacy, agreed with the authors of the December 2016 report that it probably had some efficacy, but found statements that it had substantial or 100% efficacy to be unsupportable. [ 50 ]


In April 2019, following a large-scale ring-vaccination scheme in the DRC outbreak, preliminary results showed that the vaccine had been 97.5% effective at stopping Ebola transmission, relative to no vaccination. [ 9 ] [ 10 ]


In September 2019, the US  Food and Drug Administration  (FDA) accepted Merck's  Biologics License Application  and granted  priority review  for the vaccine. [ 53 ]


In October 2019, the  European Medicines Agency  (EMA) recommended granting  conditional marketing authorization  for the rVSV-ZEBOV-GP vaccine. [ 54 ] [ 55 ] [ 56 ]


In November 2019, the European Commission granted a conditional marketing authorization to Ervebo [ 5 ] [ 57 ]  and the  World Health Organization  (WHO) prequalified an Ebola vaccine for the first time, indicating that the vaccine met WHO standards for quality, safety and efficacy, and allowing UN agencies and  GAVI  to procure vaccine for distributions. [ 58 ]


In December 2019, Ervebo was approved for use in the United States. [ 13 ]


The approval of Ervebo was supported by a study conducted in Guinea during the 2014-2016 outbreak in individuals 18 years of age and older. [ 13 ]  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 with Ervebo. [ 13 ]  This noteworthy 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. [ 13 ]  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. [ 13 ]  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. [ 13 ]


In additional studies, antibody responses to Ervebo were assessed in 477 individuals in Liberia, approximately 500 individuals in Sierra Leone and approximately 900 individuals in Canada, Spain, and the US. [ 13 ]  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. [ 13 ]


The safety of Ervebo was assessed in approximately 15,000 individuals in Africa, Europe and North America. [ 13 ]  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. [ 13 ]


The application for Ervebo in the United States was granted  priority review , a tropical disease priority review voucher, and  breakthrough therapy  designation. [ 13 ]  The US  Food and Drug Administration  (FDA) granted approval for Ervebo to Merck & Co., Inc. [ 13 ]


Merck discontinued development of the related rVSV vaccines for  Marburg virus  ( rVSV-MARV ) and  Sudan ebolavirus  ( rVSV-SUDV ). Merck returned the rights on these vaccines back to Public Health Agency of Canada. The knowledge on developing rVSV vaccines which Merck gained with  GAVI  funding remains Merck's, and cannot be used by anyone else wishing to develop a rVSV vaccine. [ 59 ]


In July 2023, the FDA expanded the approval of Ervebo for use in people aged 12 months through 17 years of age. [ 60 ]  Ervebo was approved for use in people aged 18 years of age and older in December 2019. [ 60 ]


During an  outbreak in the Democratic Republic of the Congo in 2018 , the ZEBOV vaccine was used, [ 62 ]  and what was once contact tracing which numbered 1,706 individuals (ring vaccination which totaled 3,330) was reduced to zero on June 28, 2018. [ 63 ]  The outbreak completed the required 42-day cycle on July 24. [ 64 ] [ 65 ] [ 66 ] [ 67 ] [ 68 ]


On August 1, 2018, an  EVD outbreak  was declared in North Kivu DRC. After six months the current totals stand at 735 total cases and 371 deaths; violence in the region has helped the spread of the virus. [ 69 ] [ 70 ] [ 71 ]


Preliminary results show ring vaccination with the vaccine has been highly effective at reducing Ebola transmission. [ 9 ] [ 10 ]


TKM-Ebola  was an experimental  antiviral drug  for  Ebola disease  that was developed by  Arbutus Biopharma  (formerly Tekmira Pharmaceuticals Corp.) [ 1 ]  in Vancouver, Canada. [ 2 ]  The drug candidate was formerly known as Ebola-SNALP. [ 3 ]


TKM-Ebola is a combination of  small interfering RNAs  targeting three of the seven proteins in  Ebola virus : Zaire Ebola L polymerase, Zaire Ebola membrane-associated protein (VP24), and Zaire Ebola polymerase complex protein (VP35). [ 2 ] [ 3 ]   By down-regulating these three proteins, TKM-Ebola inhibits virus replication and eliminates the infection. The drug was effective in rhesus monkeys infected with Ebola. [ 4 ]  After the Ebola outbreak in West Africa in 2014, the new variant responsible for it was isolated from several Ebola virus families and the specific genomic sequence was determined. The company re-designed TKM-Ebola and renamed it as "TKM-Ebola-Guinea". [ 5 ]


In January 2014, Tekmira started a Phase I clinical trial of TKM-Ebola to assess its safety in healthy people with a dose of 0.24 mg/kg/day for seven day treatments. The FDA placed the trial on clinical hold in July 2014 to assess results, after some subjects had flu-like responses. [ 6 ]   In August, the FDA changed the status to "partial hold", allowing the drug to be used under  expanded access  in people infected with Ebola but with the Phase I trial still suspended. [ 2 ]  In April 2015 the FDA allowed the study to resume at a lower dose. [ 7 ]


A Phase II trial started on 11 March 2015 in Sierra Leone, West Africa and stopped enrolling new subjects on 19 June 2015 after it appeared not to work. [ 8 ] [ 9 ]   In July 2015 the company announced it was changing its name to Arbutus, suspending development of the drug for Ebola and changing its focus to developing treatments for  hepatitis B virus . [ 10 ]


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


The 2013–2016  epidemic  of  Ebola virus disease , centered in  West Africa , was the most widespread  outbreak of the disease in history . It caused major loss of life and  socioeconomic  disruption in the region, mainly in  Guinea ,  Liberia  and  Sierra Leone . The first cases were recorded in Guinea in December 2013; the disease spread to neighbouring Liberia and Sierra Leone, [ 12 ]  with minor outbreaks occurring in  Nigeria  and  Mali . [ 13 ] [ 14 ]  Secondary infections of medical workers occurred in the  United States  and  Spain . [ 15 ] [ 16 ]  Isolated cases were recorded in  Senegal , [ 17 ]  the  United Kingdom  and  Italy . [ 18 ] [ 19 ]  The number of cases peaked in October 2014 and then began to decline gradually, following the commitment of substantial international resources.


It caused significant mortality, with a considerable  case fatality rate . [ 12 ] [ 18 ] [ 20 ] [ note 1 ]  By the end of the epidemic, 28,616 people had been infected; of these, 11,310 had died, for a case-fatality rate of 40%. [ 21 ]  As of 8 May 2016 [update] , the  World Health Organization  (WHO) and respective governments reported a total of 28,646 suspected cases and 11,323 deaths [ 22 ]  (39.5%), though the WHO believes that this substantially understates the magnitude of the outbreak. [ 23 ] [ 24 ]  On 8 August 2014, a  Public Health Emergency of International Concern  was declared [ 25 ]  and on 29 March 2016, the WHO terminated the Public Health Emergency of International Concern status of the outbreak. [ 26 ] [ 27 ] [ 28 ]  Subsequent flare-ups occurred; the epidemic was finally declared over on 9 June 2016, 42 days after the last case tested negative on 28 April 2016 in  Monrovia . [ 29 ]


The outbreak left about 17,000 survivors of the disease, many of whom report post-recovery symptoms termed  post-Ebola syndrome , often severe enough to require medical care for months or even years. An additional cause for concern is the apparent ability of the virus to "hide" in a recovered survivor's body for an extended period and then become active months or years later, either in the same individual or in a sexual partner. [ 30 ]  In December 2016, the WHO announced that a two-year trial of the  rVSV-ZEBOV vaccine  appeared to offer protection from the variant of EBOV responsible for the Western Africa outbreak. The vaccine is considered to be effective and is the only prophylactic that offers protection; hence, 300,000 doses have been stockpiled. [ 31 ] [ 32 ]  rVSV-ZEBOV received regulatory approval in 2019. [ 33 ] [ 34 ]


The 2013–2016 outbreak, caused by Ebola virus (EBOV), [ 35 ]  was the first anywhere in the world to reach epidemic proportions.  Extreme poverty , dysfunctional healthcare systems, distrust of government after years of armed conflict, and the delay in responding for several months, all contributed to the failure to control the epidemic. Other factors, per media reports, included local burial customs of washing the body and the unprecedented spread of Ebola to densely populated cities. [ 36 ] [ 37 ] [ 38 ] [ 39 ] [ 40 ]


It is generally believed that a one or two-year-old boy, [ 41 ] [ 42 ]  later identified as  Emile Ouamouno , who died in December 2013 in the village of  Méliandou  in Guinea, [ 43 ]  was the  index case . [ 44 ]  His mother, sister, and grandmother later became ill with similar symptoms and also died; people infected by these initial cases spread the disease to other villages. [ 45 ] [ 46 ]  These early cases were diagnosed as other conditions more common to the area and the disease had several months to spread before it became recognised as Ebola. [ 44 ] [ 45 ]


On 25 March 2014, the WHO indicated that  Guinea's Ministry of Health  had reported an outbreak of Ebola virus disease in four southeastern districts and that suspected cases in the neighbouring countries of  Liberia  and  Sierra Leone  were being investigated. In Guinea, a total of 86 suspected cases, including 59 deaths, had been reported as of 24 March. [ 47 ]  By late May, the outbreak had spread to  Conakry , Guinea's capital—a city of about two million people. [ 47 ]  On 28 May, the total number of reported cases had reached 281, with 186 deaths. [ 47 ]


In Liberia, the disease was reported in four counties by mid-April 2014 and cases in Liberia's capital  Monrovia  were reported in mid-June. [ 48 ]  The outbreak then spread to Sierra Leone and progressed rapidly. By 17 July, the total number of suspected cases in the country stood at 442, surpassing those in Guinea and Liberia. [ 49 ]  By 20 July, additional cases of the disease had been reported by the media in the  Bo District , while the first case in  Freetown , Sierra Leone's capital, was reported in late July. [ 50 ] [ 51 ]


As the epidemic progressed, a small outbreak occurred in Nigeria that resulted in 20 cases and another in Mali with seven cases. Four other countries (Senegal, Spain, the United Kingdom and the United States) also reported cases imported from Western Africa, which were quickly isolated and led to no other infections, with the exception of the US. [ 52 ] [ 53 ] [ 54 ]


On 28 January 2015, the WHO reported that for the first time since the week ending 29 June 2014, there had been fewer than 100 new confirmed cases reported in a week in the three most-affected countries. The response to the epidemic then moved to a second phase, as the focus shifted from slowing transmission to ending the epidemic. [ 55 ]  On 8 April 2015, the WHO reported a total of only 30 confirmed cases, [ 56 ]  and the weekly update for 29 July reported only seven new cases. [ 57 ]  Cases continued to gradually dwindle and on 7 October 2015, all three of the most seriously affected countries, per media reports, recorded their first joint week without any new cases. [ 58 ]  However, sporadic new cases were still being recorded, frustrating hopes that the epidemic could be declared over. [ 59 ]
On 31 March 2015, one year after the first report of the outbreak, the total number of cases was over 25,000—with over 10,000 deaths. [ 60 ]  As the main epidemic was coming to an end in December 2015, the UN announced that 22,000 children had lost one or both parents to Ebola. [ 61 ]


On 14 January 2016, after all the previously infected countries had been declared Ebola-free, the WHO reported that "all known chains of transmission have been stopped in Western Africa", but cautioned that further small outbreaks of the disease could occur. [ 62 ]  The following day, Sierra Leone confirmed its first new case since September 2015. [ 28 ]


On 25 March 2014, the WHO reported an outbreak of Ebola virus disease in four southeastern districts of Guinea with a total of 86 suspected cases, including 59 deaths. MSF assisted the Ministry of Health by establishing Ebola treatment centres in the epicentre of the outbreak. [ 47 ]  On 31 March, the  U.S. Centers for Disease Control and Prevention  (CDC) sent a team to assist in the response. [ 47 ]  Thinking that the spread of the virus had been contained, MSF closed its treatment centres in May, leaving only a skeleton staff to handle the  Macenta  region. However, in late August, according to media reports, large numbers of new cases reappeared in the region. [ 63 ]