Western African Ebola virus epidemic (2013 - 2016)

ASSOCIATIONS - People

ASSOCIATIONS - Companies and Institutions

Saved Wikipedia (July 8, 2022) for "Western African Ebola virus epidemic"

Source : [HK00A9][GDrive]

The 2013–2016 epidemic of Ebola virus disease, centered in Western 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; later, 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] In addition, 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, 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 of time 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 which offers protection; hence, 300,000 doses have been stockpiled.[31][32] rVSV-ZEBOV received regulatory approval in 2019.[33][34]

SVG file above : [HK00AA][GDrive] / JPG with white background : [HK00AB][GDrive]"Map showing death statistics as of 2014 - Created: 7 September 2014"

Overview

Ebola virus disease (commonly known as "Ebola") was first described in 1976 in two simultaneous outbreaks in the Democratic Republic of the Congo and what is now South Sudan.[35] The 2013–2016 outbreak, caused by Ebola virus (EBOV),[36] was the first anywhere in the world to reach epidemic proportions. Previous outbreaks had been brought under control in a much shorter period of time. 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.[37][38][39][40][41]

As the outbreak progressed, the media reports, many hospitals, short on both staff and supplies, were overwhelmed and closed down, leading some health experts to state that the inability to treat other medical needs may have been causing "an additional death toll [that is] likely to exceed that of the outbreak itself".[42][43] Hospital workers, who worked closely with the highly contagious body fluids of the victims, were especially vulnerable to contracting the virus; in August 2014, the WHO reported that ten per cent of the dead had been healthcare workers.[44] In September 2014, it was estimated that the affected countries' capacity for treating Ebola patients was insufficient by the equivalent of 2,122 beds; however, by December 2014 there were enough beds to treat and isolate all reported cases, although the uneven distribution of cases was resulting in serious shortfalls in some areas.[45]

The WHO has been widely criticised for its delay in taking action to address the epidemic.[46] On 8 August 2014, it declared the outbreak a public health emergency of international concern.[47] By September 2014, Médecins Sans Frontières/Doctors Without Borders (MSF), the non-governmental organisation with the largest working presence in the affected countries, had grown increasingly critical of the international response. Speaking on 3 September, the International President of MSF spoke out concerning the lack of assistance from United Nations (UN) member countries: "Six months into the worst Ebola epidemic in history, the world is losing the battle to contain it."[48] In a 26 September statement, the WHO stated that "[t]he Ebola epidemic ravaging parts of Western Africa is the most severe acute public health emergency seen in modern times" and its Director-General called the outbreak "the largest, most complex and most severe we've ever seen".[49] In March 2015, the United Nations Development Group reported that due to a decrease in trade, closing of borders, flight cancellations, and drop in foreign investment and tourism activity fuelled by stigma, the epidemic had resulted in vast economic consequences in both the affected areas in Western Africa and even in other African nations with no cases of Ebola.[50]

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.[51] On 8 April 2015, the WHO reported a total of only 30 confirmed cases,[52] and the weekly update for 29 July reported only seven new cases.[53] 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.[54] However, as of late 2015, while the large-scale epidemic had ended, according to media reports, sporadic new cases were still being recorded, frustrating hopes that the epidemic could be declared over.[55]

On 31 July 2015, the WHO announced "an extremely promising development" in the search for an effective vaccine for Ebola virus disease. While the vaccine had shown high efficacy in individuals, more conclusive evidence was needed regarding its capacity to protect populations through herd immunity.[56][57] In August 2015, after substantial progress in reducing the scale of the epidemic, the WHO held a meeting to work out a "Comprehensive care plan for Ebola survivors" and identify research needed to optimise clinical care and social well-being. Stating that "the Ebola outbreak has decimated families, health systems, economies, and social structures", the WHO called the aftermath of the epidemic "an emergency within an emergency." Of special concern is recent research that shows some Ebola survivors experience a so-called "post-Ebola Syndrome", with symptoms so severe that survivors may require medical care for months and even years.[58][59] 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.[60] On 29 March 2016, the Director-General of WHO terminated the Public Health Emergency of International Concern status of the Western African Ebola virus epidemic.[26]

Epidemiology

Outbreak

See also: Ebola virus epidemic in West Africa timeline

It is generally believed that a one or two-year-old boy,[61][62] later identified as Emile Ouamouno, who died in December 2013 in the village of Méliandou, Guéckédou Prefecture, Guinea,[63] was the index case of the Western African epidemic.[64] Scientists have deduced that bats are involved in the spread of the virus,[65] and, incidentally, the boy's home was in the vicinity of a large colony of Angolan free-tailed bats, according to media reports.[66] His mother, sister, and grandmother, per media reports later became ill with similar symptoms and also died; people infected by these initial cases spread the disease to other villages.[67][68] There was knowledge of Tai Forest virus in Côte d'Ivoire, which had resulted in one human transmission in 1994. Thus, 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.[64][67]

Monthly aggregate Ebola cases in the Western Africa epidemic 2014–15

Monthly aggregate Ebola deaths in the Western Africa epidemic 2014–15

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.[69] By late May, the outbreak had spread to Conakry, Guinea's capital—a city of about two million people.[69] On 28 May, the total number of reported cases had reached 281, with 186 deaths.[69]

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.[70] 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.[71] 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.[72][73]

As the epidemic progressed, a small outbreak occurred in Nigeria that resulted in 20 cases and another in Mali with 7 cases. Four other countries (Senegal, Spain, the United Kingdom and the United States of America) also reported cases imported from Western Africa, with widespread and intense transmission.[74][75][76]

On 31 March 2015, one year after the first report of the outbreak, the total number of cases was in excess of 25,000—with over 10,000 deaths.[77]

As the epidemic waned, following international control efforts, the edition of 8 April 2015 of the WHO's Ebola Situation Reports stated that a total of 30 cases were reported[78] and on 29 July 2015, the WHO weekly update reported only 7 cases—the lowest in more than a year.[53] In October 2015, the WHO recorded its first week without any new cases,[54] and while the large-scale epidemic appeared to have ended by late 2015, sporadic new cases continued to be reported.[55][79]

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 in the future.[80] The following day, Sierra Leone confirmed its first new case since September 2015.[28]

Countries that experienced widespread transmission

Outbreak distribution map affected part of Western Africa (17 December 2014)

Guinea

Further information: Ebola virus epidemic in Guinea

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, and MSF assisted the Ministry of Health by establishing Ebola treatment centres in the epicentre of the outbreak.[69] On 31 March, the U.S. Centers for Disease Control and Prevention (CDC) sent a five-person team to assist in the response to the outbreak.[69] Thinking that 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.[81]

In February 2015, media reported that Guinea recorded a rise in cases for the second week in a row,[82] health authorities stated that this was related to the fact that they "were only now gaining access to faraway villages", where violence had previously prevented them from entering.[83] On 14 February, violence erupted and an Ebola treatment centre near the centre of the country was destroyed. Guinean Red Cross teams said they had suffered an average of 10 attacks a month over the previous year;[84] MSF reported that acceptance of Ebola education remained low and that further violence against their workers might force them to leave.[85]

Resistance to interventions by health officials among the Guinean population remained greater than in Sierra Leone and Liberia, per media reports, raising concerns over its impact on ongoing efforts to halt the epidemic; in mid-March, there were 95 new cases and on 28 March, and a 45-day "health emergency" was declared in 5 regions of the country.[85][86] On 22 May, the WHO reported another rise in cases, per media reports,[87] which was believed to have been due to funeral transmissions;[88] on 25 May, six persons were placed in prison isolation after they were found travelling with the corpse of an individual who had died of the disease,[89] on 1 June, it was reported that violent protests in a north Guinean town at the border with Guinea-Bissau had caused the Red Cross to withdraw its workers.[90]

In late June 2015, the WHO reported that "weekly case incidence has stalled at between 20 and 27 cases since the end of May, whilst cases continue to arise from unknown sources of infection, and to be detected only after post-mortem testing of community deaths".[91] On 29 July, a sharp decline in cases was reported,[53] with only a single case, per media reports left by the end of the week,[92] the number of cases eventually plateaued at 1 or 2 cases per week after the beginning of August.[93] On 28 October, an additional 3 cases were reported in the Forécariah Prefecture by the WHO.[94] On 6 November, a media report indicated Tana village to be the last known place with Ebola in the country,[95] and on 11 November, WHO indicated that no Ebola cases were reported in Guinea; this was the first time since the epidemic began, that no cases had been reported in any country.[96] On 15 November, the last quarantined individuals were released, per media reports[97] and on 17 November, the last Ebola patient in Guinea—a 3-week-old baby—had recovered; the 42-day countdown toward the country being declared Ebola-free started on 17 November, the day after the patient yielded a second consecutive negative blood test.[98][99][100] The patient was discharged from the hospital on 28 November, per media reports[101] on 29 December 2015, upon expiration of the 42-day waiting period, the WHO declared Guinea Ebola-free.[102]

On 17 March 2016, the government of Guinea reported, per the media, that 2 people had again tested positive for Ebola virus in Korokpara,[103] it was also reported that they were from the village where members of one family had recently died from vomiting (and diarrhea).[104] On 19 March, it was also reported by the media that another individual had died due to the virus at the treatment centre in Nzerekore,[105] consequently, the country's government quarantined an area around the home where the cases took place.[106] On 22 March, the media reported that medical authorities in Guinea had quarantined 816 suspected contacts of the prior cases (more than 100 individuals were considered high-risk);[107][108] the same day, Liberia ordered its border with Guinea closed.[109] Macenta Prefecture, 200 kilometres (120 mi) from Korokpara, registered Guinea's fifth fatality due to Ebola virus disease within the same period.[110] On 29 March, it was reported that about 1,000 contacts had been identified (142 of them high-risk),[26] and on 30 March 3 more confirmed cases were reported from the sub-prefecture of Koropara.[111] On 1 April, it was reported by the media, that possible contacts, which numbered in the hundreds, had been vaccinated with an experimental vaccine using a ring vaccination approach.[112][113]

On 5 April 2016, it was reported via the media, that there had been 9 new cases of Ebola since the virus resurfaced, out of which 8 were fatal;[114] on 1 June, after the stipulated waiting period, the WHO again declared Guinea Ebola-free,[115] after which the country entered a 90-day period of heightened surveillance that was concluded on 30 August 2016.

In September 2016, findings were published suggesting that the resurgence in Guinea was caused by an Ebola survivor who, after eight months of abstinence, had sexual relations with several partners, including the first victim in the new outbreak.[116][117] The disease was also spread to Liberia by a woman who went there after her husband had died of Ebola.[118]

Sierra Leone

Further information: Ebola virus epidemic in Sierra Leone

Kenema Hospital, Sierra Leone

The first person reported infected in Sierra Leone, according to media reports, was a tribal healer who had been treating Ebola patients from across the nearby border with Guinea and who died on 26 May 2014; according to tribal tradition, her body was washed for burial, and this appears to have led to infections in women from neighbouring towns.[119] On 11 June Sierra Leone shut its borders for trade with Guinea and Liberia and closed some schools in an attempt to slow the spread of the virus;[120] on 30 July the government began to deploy troops to enforce quarantines,[121] and by 15 October the last district in Sierra Leone previously untouched by the disease had declared Ebola cases.[122]

During the first week of November reports told of a worsening situation due to intense transmission in Freetown. According to the Disaster Emergency Committee, food shortages resulting from aggressive quarantines were making the situation worse,[123] and on 4 November media reported that thousands had violated quarantine in search of food in the town of Kenema.[124] With the number of cases continuing to increase, an MSF coordinator described the situation in Sierra Leone as "catastrophic", saying, "there are several villages and communities that have been basically wiped out ... Whole communities have disappeared but many of them are not in the statistics." In mid-November the WHO reported that, while there was some evidence that the number of cases were no longer rising in Guinea and Liberia, steep increases persisted in Sierra Leone.[74]

Ebola crisis: More UK aid arrives in Sierra Leone

On 9 December 2014 news reports described the discovery of "a grim scene"—piles of bodies, overwhelmed medical personnel and exhausted burial teams—in the remote eastern Kono District.[125] On 15 December the CDC indicated that their main concern was Sierra Leone, where the epidemic had shown no signs of abating as cases continued to rise exponentially; by the second week of December, Sierra Leone had reported nearly 400 cases—more than three times the number reported by Guinea and Liberia combined. According to the CDC, "the risk we face now [is] that Ebola will simmer along, become native and be a problem for Africa and the world, for years to come".[126] On 17 December President Koroma of Sierra Leone launched "Operation Western Area Surge" and workers went door-to-door in the capital city looking for possible cases.[127][128] The operation led to a surge in reports of cases, with 403 new ones reported between 14 and 17 December.[127][129]

According to the 21 January 2015 WHO Situation Report, the case incidence was rapidly decreasing in Sierra Leone.[130][131][132] However, in February and March reports indicated a rise again in the number of cases.[133][134][135][136] The following month, the 5 April WHO report again disclosed a downward trend[137] and the WHO weekly update for 29 July reported a total of only 3 new cases, the lowest in more than a year.[53] On 17 August the country marked its first week with no new cases,[138] and one week later the last patients were released.[139] However, a new case emerged on 1 September, when a patient from Sella Kafta village in Kambia District tested positive for the disease after her death;[140] her case eventually resulted in 3 other infections among her contacts.[141]

On 14 September 2015 Sierra Leone's National Ebola Response Centre confirmed the death of a 16-year-old in a village in the Bombali District.[142] It is suspected that she contracted the disease from the semen of an Ebola survivor who had been discharged in March 2015.[143] On 27 September a new 42-day countdown began to declare the country Ebola-free,[144] which eventually occurred on 7 November 2015; thereafter, the country increased its vigilance on the Guinean border.[145][146]

Sierra Leone had entered a 90-day period of enhanced surveillance that was scheduled to end on 5 February 2016, when, on 14 January, a new Ebola death was reported in the Tonkolili District.[147][148] Prior to this case, the WHO had advised that "we still anticipate more flare-ups and must be prepared for them. A massive effort is underway to ensure robust prevention, surveillance and response capacity across all three countries by the end of March."[149] On 16 January aid workers reported that a woman had died of the virus and that she may have exposed several individuals; the government later announced that 100 people had been quarantined.[150] Investigations indicated that the deceased was a female student from Lunsar, in Port Loko District, who had gone to Kambia District on 28 December 2015 before returning symptomatic. She had also visited Bombali District to consult a herbalist, and had later gone to a government hospital in Magburaka. The WHO indicated that there were 109 contacts (28 of them high-risk), that there were another 3 missing contacts, and that the source or route of transmission that caused the fatality was unknown.[151] A second new case—confirmed by WHO spokesman Tarik Jasarevic to involve a 38-year-old relative and caregiver of the aforementioned Ebola victim—had become symptomatic on 20 Jan while under observation at a quarantine centre.[152][153] On 22 January it was reported that this patient was responding to treatment.[154] On 26 January WHO Director-General, Dr Margaret Chan officially confirmed that the outbreak was not yet over;[28] that same day, it was also reported that Ebola restrictions had halted market activity in Kambia District amid protests.[155] On 7 February 70 individuals were released from quarantine,[156] and on 8 February the last Ebola patient was also released.[157] On 17 February the WHO indicated that 2,600 Ebola survivors had accessed health assessments and eye examinations.[158]

On 4 February 2016 the last known case tested negative for a second consecutive time and Sierra Leone commenced another 42-day countdown towards being declared Ebola-free.[159][160] On 17 March 2016 the WHO announced that the Sierra Leone flare-up was over, and that no other chains of transmission were known to be active at that time.[161] The media reported that Sierra Leone then entered a 90-day period of heightened surveillance, which concluded on 15 June 2016, and it was reported that by 15 July the country had discontinued testing corpses for the virus.[162]

Liberia

Further information: Ebola virus epidemic in Liberia

An Ebola treatment unit in Liberia

In Liberia, the disease was reported in both Lofa and Nimba counties in late March 2014.[163] On 27 July, President Ellen Johnson Sirleaf announced that Liberia would close its borders, with the exception of a few crossing points such as Roberts International Airport, where screening centres would be established.[164] Schools and universities were closed,[165][166] and the worst-affected areas in the country were placed under quarantine.[167]

With only 50 physicians in the entire country—one for every 70,000 citizens—Liberia was already in a healthcare crisis.[168] In September, the CDC reported that some hospitals had been abandoned, while those still functioning lacked basic facilities and supplies.[169] In October, the Liberian ambassador in Washington was reported as saying that he feared that his country may be "close to collapse";[168] by 24 October, all 15 counties had reported Ebola cases.[5][170]

By November 2014, the rate of new infections in Liberia appeared to be declining and the state of emergency was lifted. The drop in cases was believed to be related to an integrated strategy combining isolation and treatment with community behaviour change, including safe burial practices, case finding and contact tracing.[171][172] Roselyn Nugba-Ballah, leader of the Safe & Diginified Burial Practices Team during the crisis, was awarded the Florence Nightingale Medal in 2017 for her work during the crisis.[173]

In January 2015, the MSF field coordinator reported that Liberia was down to only 5 confirmed cases.[174] In March, after two weeks of not reporting any new cases, 3 new cases were confirmed.[175] On 8 April, a new health minister was named in an effort to end Ebola in the country and on 26 April, MSF handed the Ebola treatment facility, ELWA-3, over to the government.[176] On 30 April, the US shut down a special Ebola treatment unit in Liberia.[177] The last known case of Ebola died on 27 March,[178] and the country was officially declared Ebola-free on 9 May 2015, after 42 days without any further cases being recorded. The WHO congratulated Liberia saying, "reaching this milestone is a testament to the strong leadership and coordination of Liberian President Ellen Johnson Sirleaf and the Liberian Government, the determination and vigilance of Liberian communities, the extensive support of global partners, and the tireless and heroic work of local and international health teams."[179] As at May 2015, the country remained on high alert against recurrence of the disease.[180][181][182]

After three months with no new reports of cases, on 29 June Liberia reported that the body of a 17-year-old boy, who had been treated for malaria, tested positive for Ebola. The WHO said the boy had been in close contact with at least 200 people,[183] who they were following up, and that "the case reportedly had no recent history of travel, contact with visitors from affected areas, or funeral attendance." A second case was confirmed on 1 July.[184][185] After a third new case was confirmed on 2 July, and it was discovered that all 3 new cases had shared a meal of dog meat, researchers looked at the possibility that the meat may have been involved in the transfer of the virus.[186][187] Testing of the dog's remains, however, was negative for the Ebola virus.[188] By 9 July 3 more cases were discovered, bringing the total number of new cases to 5, all from the same area.[189] On 14 July, a woman died of the disease in the county of Montserrado, bringing the total to 6.[190] On 20 July, the last patients were discharged,[191] and on 3 September 2015, Liberia was declared Ebola-free again.[192]

After two months of being Ebola-free, a new case was confirmed on 20 November 2015, when a 15-year-old boy was diagnosed with the virus[193][194] and two family members subsequently tested positive as well.[195][196] Health officials were concerned because the child had not recently travelled or been exposed to someone with Ebola and the WHO stated that "we believe that this is probably again, somehow, someone who has come in contact with a virus that had been persisting in an individual, who had suffered the disease months ago." Two staff of the CDC were sent to the country to help ascertain the cause of the new cases.[197] The infected boy died on 24 November,[198] and on 3 December 2 remaining cases were released after recovering from the disease.[199] The 42-day countdown toward Liberia being declared Ebola-free, for the third time, started on 4 December 2015.[200] On 16 December, the WHO reaffirmed that the cases in Liberia were the result of re-emergence of the virus in a previously infected person,[201] and there was speculation that the boy may have been infected by an individual who became infectious once more due to pregnancy, which may have weakened her immune system.[202] On 18 December, the WHO indicated that it still considered Ebola in Western Africa a public health emergency, though progress had been made.[203]

After having completed the 42-day time period, Liberia was declared free from the virus on 14 January 2016, effectively ending the outbreak that had started in neighbouring Guinea 2 years earlier. Liberia began a 90-day period of heightened surveillance, scheduled to conclude on 13 April 2016,[204] but on 1 April, it was reported that a new Ebola fatality had occurred,[205] and on 3 April, a second case was reported in Monrovia.[206] On 4 April, it was reported that 84 individuals were under observation due to contact with the 2 confirmed Ebola cases.[207] By 7 April, Liberia had confirmed 3 new cases since the virus resurfaced and a total of 97 contacts, including 15 healthcare workers, were being monitored.[208] The index case of the new flareup was reported to be the wife of a patient who died from Ebola in Guinea; she had travelled to Monrovia after the funeral but died from the disease.[209] The outbreak in Guinea, in turn, had begun when a man, who had survived Ebola, had sexual intercourse with a woman and passed the virus to her, even though he had recovered more than a year earlier.[116][117]

On 29 April, WHO reported that Liberia had discharged the last patient and had begun the 42-day countdown to be declared Ebola-free once more. According to the WHO, tests indicated that the flare-up was likely due to contact with a prior Ebola survivor's infected body fluids.[118] On 9 June, the flare-up was declared over, and the country Ebola-free, due to the passage of the 42-day period;[210][211] Liberia then entered a 90-day period of heightened surveillance, which ended on 7 September 2016. In early July 2016, a trial for males with detectable Ebola RNA in semen, started.[212]

Western African countries with limited local cases

Senegal

In March 2014, the Senegal Ministry of Interior closed its southern border with Guinea,[213] but on 29 August, the health minister announced the country's first case – a university student from Guinea who was being treated in a Dakar hospital.[214] The patient was a native of Guinea who had travelled to Dakar, arriving on 20 August. On 23 August, he sought medical care for symptoms including diarrhoea, and vomiting plus signs of fever. He received treatment for malaria but did not improve and left the facility. Still experiencing the same symptoms, on 26 August he was referred to a specialised facility for infectious diseases, and subsequently hospitalised.[214]

On 28 August 2014, authorities in Guinea issued an alert informing their medical services and neighbouring countries that a person who had been in close contact with an Ebola-infected patient had escaped their surveillance system. The alert prompted testing for Ebola at the Dakar laboratory, and the positive result launched an investigation, triggering urgent contact tracing.[214] On 10 September, it was reported that the student had recovered but health officials continued to monitor his contacts for 21 days.[215] No further cases were reported,[216] and on 17 October 2014, the WHO officially declared that the outbreak in Senegal had ended.[5]

The WHO officially commended the Senegalese government, and in particular the President Macky Sall and the Minister of Health, Dr Awa Coll-Seck, for their response in quickly isolating the patient and tracing and following up 74 contacts, as well as for their public awareness campaign. This acknowledgement was also extended to MSF and the CDC for their assistance.[217]

Nigeria

Further information: Ebola virus disease in Nigeria

The first case in Nigeria was a Liberian-American, who flew from Liberia to Nigeria's most populated city of Lagos on 20 July 2014. On 6 August 2014, the Nigerian health minister told reporters that one of the nurses that attended to the Liberian had died from the disease. 5 newly confirmed cases were being treated at an isolation ward.[218]

On 22 September 2014, the Nigerian health ministry announced, "As of today, there is no case of Ebola in Nigeria." According to the WHO, 20 cases and 8 deaths were confirmed, including the imported case, who also died. 4 of the dead were health workers who had cared for the index case.[219]

The WHO's representative in Nigeria officially declared the country Ebola-free on 20 October 2014, after no new active cases were reported in the follow up contacts, stating it was a "spectacular success story".[220] Nigeria was the first African country to be declared Ebola free.[221] This was largely due to the early quarantine efforts of Dr. Ameyo Stella Adadevoh at First Consultants Medical Centre in Lagos.[222]

Mali

Malian regions with Ebola cases (Kayes/Bamako), November 2014

Further information: Ebola virus disease in Mali

On 23 October 2014, the first case of Ebola virus disease in Mali was confirmed in the city of Kayes—a two-year-old girl who had arrived with a family group from Guinea, and died the next day.[223][224] Her father had worked for the Red Cross in Guinea and also in a private health clinic; he had died earlier in the month, likely from an Ebola infection contracted in the private clinic. It was later established that a number of family members had also died of Ebola. The family had returned to Mali after the father's funeral via public bus and taxi—a journey of more than 1,200 kilometres (750 mi). All contacts were followed for 21 days, with no further spread of the disease reported.[225]

On 12 November 2014, Mali reported deaths from Ebola in an outbreak unconnected with the first case in Kayes. The first probable case was an imam who had fallen ill on 17 October in Guinea and was transferred to the Pasteur Clinic in Mali's capital city, Bamako, for treatment. He was treated for kidney failure but was not tested for Ebola; he died on 27 October and his body returned to Guinea for burial.[226] A nurse and a doctor who had treated the imam subsequently fell ill with Ebola and died.[227][228] The next 3 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. On 22 November, the final case related to the imam was reported—a friend of the Pasteur Clinic nurse who had died from the Ebola virus.[229] On 12 December, 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.[230] On 16 December, Mali released the final 13 individuals who were being quarantined[231] and 24 days later (18 January 2015) without new cases, the country was declared Ebola-free.[13]

Other countries with limited local cases

  • United Kingdom

      • Further information: Ebola virus disease in the United Kingdom

      • On 29 December 2014, Pauline Cafferkey, a British aid worker who had just returned to Glasgow from Sierra Leone, was diagnosed with Ebola.[232] She was treated and declared to be free of infection and released from hospital on 24 January 2015.[9][233] On 8 October, she was readmitted for complications caused by the virus[234] and was in "serious" condition, according to a hospital report. On 14 October, her condition was listed as "critical"[235] and 58 individuals were being monitored and 25 received an experimental vaccination, being close contacts.[236][237] On 21 October, it was reported that she had been diagnosed with meningitis caused by the virus persisting in her brain.[238] On 12 November, she was released from hospital after making a full recovery.[239] However, on 23 February, Ms. Cafferkey was admitted for a third time, "under routine monitoring by the Infectious Diseases Unit ... for further investigations", according to a spokesperson.[240][241]

  • Italy

      • On 12 May 2015, it was reported that a nurse, who had been working in Sierra Leone, had been diagnosed with Ebola after returning home to the Italian island of Sardinia. He was treated at Spallanzani Hospital, the national reference centre for Ebola patients.[242] On 10 June, it was reported that he had recovered and was disease-free and he was released from hospital.[243]

  • Spain

      • Further information: Ebola virus disease cases in Spain

      • On 5 August 2014, the Brothers Hospitallers of Saint John of God confirmed that Brother Miguel Pajares, who had been volunteering in Liberia, had become infected. He was evacuated to Spain and died on 12 August.[244] 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.[245]

      • In October 2014, a nursing assistant, Teresa Romero, who had cared for these patients became unwell and on 6 October tested positive for Ebola,[246][247] making this the first confirmed case of Ebola transmission outside of Africa. On 19 October, it was reported that Romero had recovered, and on 2 December the WHO declared Spain Ebola-free following the passage of 42 days since Teresa Romero was found to be cured.[248]

  • United States

      • Further information: Ebola virus cases in the United States

      • On 30 September 2014, the CDC declared its first case of Ebola virus disease. It disclosed that Thomas Eric Duncan became infected in Liberia and travelled to Dallas, Texas on 20 September. On 26 September, he fell ill and sought medical treatment, but was sent home with antibiotics. He returned to the hospital by ambulance on 28 September and was placed in isolation and tested for Ebola.[249][250] He died on 8 October.[251] Two cases stemmed from Duncan, when two nurses that had treated him tested positive for the virus on 10 and 14 October[252][253] and ended when they were declared Ebola-free on 24 and 22 October, respectively.[254][255]

      • A fourth case was identified on 23 October 2014, when Craig Spencer, an American physician who had returned to the United States after treating Ebola patients in Western Africa, tested positive for the virus.[256] This case, however, had no relation to those originating from Duncan. Spencer recovered and was released from hospital on 11 November.[257]

Countries with medically evacuated cases

A number of people who had become infected with Ebola were medically evacuated for treatment in isolation wards in Europe or the US. They were mostly health workers with one of the NGOs in Western Africa. With the exception of a single isolated case in Spain, no secondary infections occurred as a result of the medical evacuations. The US accepted four evacuees and three were flown to Germany.[258][259][260] France,[261][262] Italy,[263] the Netherlands,[264] Norway,[265][266] Switzerland,[267] and the United Kingdom received two patients (and five who were exposed).[268][269]

Unrelated outbreak in the Democratic Republic of the Congo

Further information: 2014 Democratic Republic of the Congo Ebola virus outbreak

In August 2014, the WHO reported an outbreak of Ebola virus in the Boende District, part of the northern Équateur province of the Democratic Republic of the Congo (DRC), where 13 people were reported to have died of Ebola-like symptoms.[270] Genetic sequencing revealed that this outbreak was caused by the Zaire Ebola species, which is native to the DRC; there have been seven previous Ebola outbreaks in the country since 1976. The virology results and epidemiological findings indicated no connection to the epidemic in Western Africa.[270][271]

The index case was initially reported to have been a woman from Ikanamongo Village, who became ill with symptoms of Ebola after she had butchered a bush animal.[270][272] However, later findings suggested that there may have been several previous cases, and it was reported that pigs in the village may have been infected with Ebola some time before the first human case occurred.[273] The WHO declared the outbreak over on 21 November 2014, after a total of 66 cases and 49 deaths.[274][275]

Virology

See also: Ebola virus disease § Virology, and Ebola virus

Ebola virus particles using electron micrograph

Ebola virus disease is caused by four of six viruses classified in the genus Ebolavirus. Of the four disease-causing viruses, Ebola virus (formerly and often still called the Zaire Ebola virus) is dangerous and is the virus responsible for the epidemic in Western Africa.[276][277] Since the discovery of the viruses in 1976, when outbreaks occurred in South Sudan (then Sudan) and Democratic Republic of the Congo (then Zaire), Ebola virus disease had been confined to areas in Middle Africa, where it is native. With the current outbreak, it was initially thought that a new species native to Guinea might be the cause, rather than being imported from Middle to Western Africa.[64] However, further studies have shown that the outbreak was likely caused by an Ebola virus lineage that spread from Middle Africa via an animal host within the last decade, with the first viral transfer to humans in Guinea.[276][278]

In a study done by Tulane University, the Broad Institute and Harvard University, in partnership with the Sierra Leone Ministry of Health and Sanitation, researchers provided information about the origin and transmission of the Ebola virus that set the Western African outbreak apart from previous ones, including 341 genetic changes in the virion.[276] Five members of the research team became ill and died from Ebola before the study was published in August 2014.[276]

Ebola virus particles

In a report released in August 2014, researchers tracked the spread of Ebola in Sierra Leone from the group first infected—13 women who had attended the funeral of the traditional healer, where they contracted the disease—giving them a unique opportunity to track how the virus had changed. This provided "the first time that the real evolution of the Ebola virus [could] be observed in humans." The research showed that the outbreak in Sierra Leone was sparked by at least two distinct lineages introduced from Guinea at about the same time. It is not clear whether the traditional healer was infected with both variants, or if perhaps one of the women attending the funeral was independently infected. As the Sierra Leone epidemic progressed, one virus lineage disappeared from patient samples, while a third one appeared.[279][280][281][282]

In January 2015, the media stated researchers in Guinea had reported mutations in the virus samples that they were looking at. According to them, "we've now seen several cases that don't have any symptoms at all, asymptomatic cases. These people may be the people who can spread the virus better, but we still don't know that yet. A virus can change itself to [become] less deadly, but more contagious and that's something we are afraid of."[283] A 2015 study suggested that accelerating the rate of mutation of the Ebola virus could make the virus less capable of infecting humans. In this animal study, the virus became practically non-viable, consequently increasing survival.[284]

Transmission

See also: Ebola virus disease § Transmission

Animal to human transmission

The life cycles of the Ebolavirus

The initial infection is believed to occur after an Ebola virus is transmitted to a human by contact with an infected animal's body fluids. Evidence strongly implicates bats as the reservoir hosts for ebolaviruses (however, despite considerable research, infectious ebolaviruses have never been recovered from bats).[285][286] Bats drop partially eaten fruit and pulp, then land mammals such as gorillas and duikers feed on this fallen fruit. This chain of events forms a possible indirect means of transmission from the natural host to animal populations.[287] As primates in the area were not found to be infected and fruit bats do not live near the location of the initial zoonotic transmission event in Meliandou, Guinea, it is suspected that the index case occurred after a child had contact with an insectivorous bat from a colony of Angolan free-tailed bats near the village.[288]

On 12 January, the journal Nature reported that the virus emergence could be found by studying how bush-meat hunters interacted with the ecosystem.[289] The continent of Africa has experienced deforestation in several areas or regions; this may contribute to recent outbreaks, including this epidemic, as initial cases have been in the proximity of deforested lands where fruit-eating bats natural habitat may be affected, though 100% evidence does not as yet exist.[290][291]

Human to human transmission

Prior to this outbreak, it was believed that human-to-human transmission occurred only via direct contact with blood or bodily fluids from an infected person who is showing symptoms of infection, by contact with the body of a person who had died of Ebola, or by contact with objects recently contaminated with the body fluids of an actively ill infected person.[292][293] It is now known that the Ebola virus can be transmitted sexually. Over time, studies have suggested that the virus can persist in seminal fluid, with a study released in September 2016 suggesting that the virus may survive more than 530 days after infection.[117] EBOV RNA in semen is not the same situation as perseverance of EBOV in semen, however the "clinical significance of low levels of virus RNA in convalescent" individuals who are healthy is unknown.[294][295]

In September 2014, the WHO had reported: "No formal evidence exists of sexual transmission, but sexual transmission from convalescent patients cannot be ruled out. There is evidence that live Ebola virus can be isolated in seminal fluids of convalescent men for 82 days after onset of symptoms. Evidence is not available yet beyond 82 days."[296] In April 2015, following a report that the RNA virus had been detected in a semen sample six months after a man's recovery, the WHO issued a statement: "For greater security and prevention of other sexually transmitted infections, Ebola survivors should consider correct and consistent use of condoms for all sexual acts beyond three months until more information is available."[297][298]

The WHO based their new recommendations on a March 2015 case, in which a Liberian woman who had no contact with the disease other than having had unprotected sex with a man who had had the disease in October 2014, was diagnosed with Ebola. While no evidence of the virus was found in his blood, his semen revealed Ebola virus RNA closely matching the variant that infected the woman. However, "doctors don't know if there was any fully formed (and therefore infectious) virus in the guy's semen." It is known that testes are protected from the body's immune system to protect the developing sperm, and it is thought that this same protection may allow the virus to survive in the testes for an unknown time.[299]

On 14 September 2015, the body of a girl who had died in Sierra Leone tested positive for Ebola[142] and it was suspected that she may have contracted the disease from the semen of an Ebola survivor who was discharged in March 2015.[143] According to some news reports, a new study to be published in the New England Journal of Medicine indicated that the RNA virus could remain in the semen of survivors for up to six months,[300][301] and according to other researchers, the RNA virus could continue in semen for 82 days and maybe longer. Furthermore, Ebola RNA had been found up to 284 days post-onset of viral symptoms.[302]

Containment difficulties

One of the primary reasons for the spread of the disease is the low-quality, functioning health systems in the parts of Africa where the disease occurs.[303] The risk of transmission is increased among those caring for people infected. Recommended measures when caring for those who are infected include medical isolation via the proper use of boots, gowns, gloves, masks and goggles, and sterilizing all equipment and surfaces.[304]

One of the biggest dangers of infection faced by medical staff requires their learning how to properly suit up and remove personal protective equipment. Full training for wearing protective body clothing can take 10 to 14 days.[305] Even with proper isolation equipment available, working conditions such as lack of running water, climate control, and flooring have made direct care difficult. Two American health workers who contracted the disease and later recovered said that to the best of their knowledge, their team of workers had been following "to the letter all of the protocols for safety that were developed by the [CDC] and WHO", including a full body coverall, several layers of gloves, and face protection including goggles. One of the two, a physician, had worked with patients, but the other was assisting workers to get in and out of their protective gear while wearing protective gear herself.[306]

Difficulties in attempting to halt transmission have also included the multiple disease outbreaks across country borders.[307] Dr Peter Piot, the scientist who co-discovered the Ebola virus, stated that the outbreak was not following its usual linear patterns as mapped out in earlier outbreaks—this time the virus was "hopping" all over the Western African epidemic region.[81] Furthermore, most past epidemics had occurred in remote regions, but this outbreak spread to large urban areas, which had increased the number of contacts an infected person might have and made transmission harder to track and break.[308] On 9 December, a study indicated that a single individual introduced the virus into Liberia, causing the most cases of the disease in that country.[309]

Containment and control

Main article: Prevention of viral hemorrhagic fever

See also: Ebola virus disease § Prevention

Nigerian doctors training on PPE by WHO

In August 2014, the WHO published a road map of the steps required to bring the epidemic under control and to prevent further transmission of the disease within Western Africa; the coordinated international response worked towards realising this plan.[310]

Surveillance and contact tracing

Contact tracing is an essential method of preventing the spread of the disease, this requires effective community surveillance so that a possible case of Ebola can be registered and accurately diagnosed as soon as possible, and subsequently finding everyone who has had close contact with the case and tracking them for 21 days. However, this requires careful record-keeping by properly trained and equipped staff.[311][312] WHO Assistant Director-General for Global Health Security, Keiji Fukuda, said on 3 September 2014, "We don't have enough health workers, doctors, nurses, drivers, and contact tracers to handle the increasing number of cases."[313] There was a massive effort to train volunteers and health workers, sponsored by United States Agency for International Development (USAID).[314] According to WHO reports, 25,926 contacts from Guinea, 35,183 from Liberia and 104,454 from Sierra Leone were listed and traced as of 23 November 2014.[75] According to one study, it is important to have a public awareness campaign to inform the affected community about the importance of contact tracing, so that true information can be obtained from the community.[315]

Community awareness

See also: Cultural effects of the Ebola crisis

To reduce the spread, the WHO recommended raising community awareness of the risk factors for Ebola infection and the protective measures individuals can take.[316] These include avoiding contact with infected people and regular hand washing using soap and water.[317] A condition of extreme poverty exists in many of the areas that experienced a high incidence of infections. According to the director of the NGO Plan International in Guinea, "The poor living conditions and lack of water and sanitation in most districts of Conakry pose a serious risk that the epidemic escalates into a crisis. People do not think to wash their hands when they do not have enough water to drink."[318] One study showed that once people had heard of the Ebola virus disease, hand washing with soap and water improved, though socio-demographic factors influenced hygiene.[319]

A number of organisations enrolled local people to conduct public awareness campaigns among the communities in Western Africa.[320] "... what we mean by social mobilization is to try to convey the right messages, in terms of prevention measures, adapted to the local context—adapted to the cultural practices in a specific area," said Vincent Martin, FAO's representative in Senegal.[321]

Denial in some affected countries also made containment efforts difficult.[322] Language barriers and the appearance of medical teams in protective suits sometimes increased fears of the virus.[323] In Liberia, a mob attacked an Ebola isolation centre, stealing equipment and "freeing" patients while shouting "There's no Ebola."[324] Red Cross staff were forced to suspend operations in southeast Guinea after they were threatened by a group of men armed with knives.[325] In September, in the town of Womey in Guinea, suspicious inhabitants wielding machetes murdered at least eight aid workers and dumped their bodies in a latrine.[326]

An August 2014 study found that nearly two-thirds of Ebola cases in Guinea were believed to be due to burial practices including washing of the body of one who had died.[39][40][41][61][72][327] In November, WHO released a protocol for the safe and dignified burial of people who die from Ebola virus disease. It encouraged the inclusion of family and clergy, and gave specific instructions for Muslim and Christian burials.[328] In the 21 January 2015 WHO road map update, it was reported that 100% of districts in Sierra Leone and 71% of districts in Guinea had a list of key religious leaders who promoted safe and dignified burials.[329] Speaking on 27 January 2015, Guinea's Grand Imam, the country's highest cleric, gave a very strong message saying, "There is nothing in the Koran that says you must wash, kiss or hold your dead loved ones," and he called on citizens to do more to stop the virus by practising safer burying rituals that do not compromise tradition.[330]

During the height of the epidemic, most schools in the three most affected countries were shut down and remained closed for several months. During the period of closure UNICEF and its partners established strict hygiene protocols to be used when the schools were reopened in January 2015. They met with thousands of teachers and administrators to work out hygiene guidelines. Their efforts included installing hand-washing stations and distributing millions of bars of soap and chlorine and plans for taking the temperature of children and staff at the school gate. Their efforts were complicated by the fact that less than 50% of the schools in these three countries had access to running water. In August 2015, UNICEF released a report that stated, "Across the three countries, there have been no reported cases of a student or teacher being infected at a school since strict hygiene protocols were introduced when classes resumed at the beginning of the year after a months-long delay caused by the virus."[331] Researchers presented evidence indicating that infected people that lived in low socioeconomic areas were more likely to transmit the virus to other socioeconomic status (SES) communities, in contrast to individuals in higher SES areas who were infected as well.[332] Another study showed that, in Guinea, a satisfactory knowledge had not altered the level of comprehensive knowledge about the virus. As a consequence, the high level of misinterpretation was responsible for a low comprehensive knowledge about the virus; 82% of individuals believed that Ebola was the result of a virus (36.2% thought that a higher power had caused it).[333] A study on Nigeria's success story stated that, in this case, a prompt response by the government and proactive public health measures had resulted in the quick control of the outbreak.[334]

During the height of the crisis, Wikipedia's Ebola page received 2.5 million page views per day, making Wikipedia one of the world's most highly used sources of trusted medical information regarding the disease.[335][336]

Travel restrictions and quarantines

Quarantine travel pass for individuals providing assistance

There was serious concern that the disease would spread further within Western Africa or elsewhere in the world, such as:

  • Western Africa On 8 August 2014, a cordon sanitaire, a disease-fighting practice that forcibly isolates affected regions, was established in the triangular area where Guinea, Liberia, and Sierra Leone are separated only by porous borders and where 70 per cent of the known cases had been found.[337] This was subsequently replaced by a series of simple checkpoints for hand-washing and measuring body temperature on major roads throughout the region, manned either by local volunteers or by the military.[338][339]

  • International Many countries considered imposing travel restrictions to or from the region. On 2 September 2014, WHO Director-General Margaret Chan advised against this, saying that they were not justified and that they would prevent medical experts from entering the affected areas. She also stated that they were "marginalizing the affected population and potentially worsening the crisis". UN officials working on the ground also criticised the travel restrictions, saying the solution was "not in travel restrictions but in ensuring that effective preventive and curative health measures are put in place".[340] MSF also spoke out against the closure of international borders, calling them "another layer of collective irresponsibility" and added: "The international community must ensure that those who try to contain the outbreak can enter and leave the affected countries if need be."[48]

In December 2015, during the 8th meeting of WHO's "IHR Emergency Committee regarding Ebola", it spoke out against further travel restrictions saying: "The Committee remains deeply concerned that 34 countries still enact inappropriate travel and transport measures and highlights the need to immediately terminate any such measures due to their negative impact, particularly on recovery efforts."[341] In December 2015, the CDC indicated that it would no longer make the recommendation for US citizens going to Sierra Leone to be extra careful. However, the CDC did further indicate that individuals travelling to the country should take precaution with sick people and body fluids. Additionally, individuals travelling to the country should avoid contact with animals.[342]

  • Returning health workers There was concern that people returning from affected countries, such as health workers and reporters, may have been incubating the disease and become infectious after arriving. Guidelines for returning workers were issued by a number of agencies, including the CDC,[343] MSF,[344] Public Health England,[345] and Public Health Ontario.[346]

Treatment

See also: Ebola virus disease treatment research and Ebola vaccine

Practising taking blood in PPE

No proven Ebola virus-specific treatment presently exists;[347][348] however, measures can be taken to improve a patient's chances of survival.[349] Ebola symptoms may begin as early as two days or as long as 21 days after one is exposed to the virus. Symptoms usually begin with a sudden influenza-like illness characterised by feeling tired, and pain in the muscles and joints. Later symptoms may include headache, nausea, and abdominal pain; this is often followed by severe vomiting and diarrhoea.[350][351] In past outbreaks, it has been noted that some patients bleed internally and/or externally; however data published in October 2014 showed that this had been a rare symptom in the Western African outbreak.[352] Another study published in October 2014 suggested that a person's genetic makeup may play a major role in determining how an infected person's body reacts to the disease, with some infected people experiencing mild or no symptoms while others progress to a very severe stage that includes bleeding.[353]

Without fluid replacement, such an extreme loss of fluids leads to dehydration, which in turn may lead to hypovolaemic shock—a condition in which there isn't enough blood for the heart to pump through the body. If a patient is alert and is not vomiting, oral rehydration therapy may be instituted, but patients who are vomiting or are delirious must be hydrated with intravenous (IV) therapy.[347][354] However, administration of IV fluids is difficult in the African environment. Inserting an IV needle while wearing three pairs of gloves and goggles that may be fogged is difficult, and once in place, the IV site and line must be constantly monitored. Without sufficient staff to care for patients, needles may become dislodged or pulled out by a delirious patient. A patient's electrolytes must be closely monitored to determine correct fluid administration, for which many areas did not have access to the required laboratory services.[355]

Treatment centres were overflowing with patients while others waited to be admitted; dead patients were so numerous that it was difficult to arrange for safe burials. Based on many years of experience in Africa—and several months working in the present epidemic—MSF took a conservative approach. While using IV treatment for as many patients as they could manage, they argued that improperly managed IV treatment was not helpful and may even kill a patient when not properly managed. They also said that they were concerned about further risk to already overworked staff.[355] In 2015 experts studied the mortality rates of different treatment settings, and given the wide differences in variables that affected outcomes, adequate information had not yet been gathered to make a definitive statement about what constituted optimal care in the Western African setting.[356] Paul Farmer of Partners in Health, an NGO that only as of January 2015 had begun to treat Ebola patients, strongly supported IV therapy for all Ebola patients stating: "What if the fatality rate isn't the virulence of disease but the mediocrity of the medical delivery?" Farmer suggested that every treatment facility should have a team that specializes in inserting IVs, or better yet, peripherally inserted central catheter lines.[355] In 2020, viewing the information gathered from the pandemic Farmer noted that there were almost no deaths in the U.S. and European patients because they had received optimal care.[357]

Prognosis

Ebola virus disease has a high case fatality rate (CFR), which in past outbreaks varied between 25% and 90%, with an average of about 50%.[358] The epidemic caused significant mortality, with reported CFRs of up to 70%.[12][20][18][359] Care settings that have access to medical expertise may increase survival by providing good maintenance of hydration, circulatory volume, and blood pressure.[352]

The disease affects males and females equally and the majority of those that contract Ebola disease are between 15 and 45 years of age.[12] For those over 45 years, a fatal outcome was more likely in the Western African epidemic, as was also noted in preceding outbreaks.[352] Only rarely do pregnant women survive—a midwife who worked with MSF in a Sierra Leone treatment centre stated that she knew of "no reported cases of pregnant mothers and unborn babies surviving Ebola in Sierra Leone."[360] In September 2015, the WHO issued pregnancy guidance information entitled, "Interim Guidance on Ebola Virus Disease in Pregnancy."[361]

It has been suggested that the loss of human life was not limited to Ebola victims alone. Many hospitals had to shut down, leaving people with other medical needs without care. A spokesperson for the UK-based health foundation, the Wellcome Trust, said in October 2014 that "the additional death toll from malaria and other diseases [is] likely to exceed that of the outbreak itself".[42] Dr Paul Farmer stated: "Most of Ebola's victims may well be dying from other causes: women in childbirth, children from diarrhoea, people in road accidents or from trauma of other sorts."[43] As the epidemic drew to a close in 2015, a report from Sierra Leone showed that the fear and mistrust of hospitals generated by the epidemic had resulted in an 11% decline in facility-based births, and that those receiving care before or after birth fell by about a fifth. Consequently, between May 2014 and April 2015, the deaths of women during or just after childbirth rose by almost a third and those of newborns by a quarter, compared to the previous year.[362]

Research suggests that many Ebola infections are asymptomatic, meaning that some infected people show no symptoms of the disease. For example, two studies done on previous outbreaks showed that 71% of seropositive individuals did not have the clinical disease in one outbreak and another study reported that 46% of asymptomatic close contacts of patients with Ebola were seropositive.[363] On 22 January, the WHO issued Clinical Care for survivors of Ebola Virus Disease: interim guidance. The guidance covers specific issues like musculoskeletal pain, which is reported in up to 75% of survivors. The pain is symmetrical and more pronounced in the morning, with the larger joints most affected. There is also possible periarticular tenosynovitis affecting the shoulders. The WHO guidelines advise to distinguish non-inflammatory arthralgia from inflammatory arthritis. With regard to ocular problems, sensitivity to light and blurry vision have been indicated among survivors. Among the aftereffects of Ebola virus disease, uveitis and optic nerve disease could appear after an individual is discharged. Ocular problems could threaten sight in survivors, thus the need for prompt treatment. In treating such individuals, the WHO recommends urgent intervention if uveitis is suspected; this consists mainly of prednisone (a corticosteroid). Hearing loss has been reported in Ebola survivors 25% of the time. Treatment, in the case of acute labyrinthitis (inner ear disorder), should be given within 10 days of the onset of symptoms and prochlorperazine, a vestibular sedative, may be administered for vertigo.[364]

Post-Ebola virus syndrome

See also: Post-Ebola virus syndrome

There are at least 17,000 people who have survived infection from the Ebola virus in Western Africa; some of them have reported lingering health effects.[365] In early November, a WHO consultant reported: "Many of the survivors are discharged with the so-called Post-Ebola Syndrome. We want to ascertain whether these medical conditions are due to the disease itself, the treatment given or chlorine used during disinfection of the patients. This is a new area for research; little is known about the post-Ebola symptoms."[366][367]

In February 2015, a Sierra Leone physician said about half of the recovered patients she saw reported declining health and that she had seen survivors go blind.[368][369] In May 2015, a senior consultant to the WHO said that the reports of eye problems were especially worrying because "there are hardly any ophthalmologists in Western Africa, and only they have the skills and equipment to diagnose conditions like uveitis that affect the inner chambers of the eye."[370]

The medical director of a hospital in Liberia reported that he was seeing health problems in patients who had been in recovery for as long as nine months. Problems he was seeing included chronic pain, sometimes so severe that walking was difficult; eye problems, including uveitis; and headaches as the most common physical symptoms. "They're still very severe and impacting their life every day. These patients will need medical care for months and maybe years." A physician from the Kenema hospital in Sierra Leone reported similar health difficulties.[370]

In December 2014, a British aid worker who had just returned from Sierra Leone was diagnosed with Ebola. She was treated with survivors' blood plasma and experimental drugs and declared free of disease in January 2015. However, in October 2015, she again became critically ill and was diagnosed with meningitis. In this unprecedented case it is thought that the virus remained in her brain replicating at a very low level until it had replicated to a degree capable of causing clinical meningitis. The woman was treated and in November 2015 it was reported that she had recovered.[238][239]

In terms of medical literature that are reviews, few articles have been published, such as Shantha, et al. which discusses management of panuveitis and iris heterochromia.[371]

Ebola survivor studies[edit]

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".[363]

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.[372]

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.[373]

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".[365]

Level of care

WHO workers gear up to go to Ebola ward Nigeria, 2014

In June 2014, it was reported that local authorities did not have the resources to contain the disease, with health centres closing and hospitals becoming overwhelmed.[374] There were also reports that adequate personal protection equipment was not being provided for medical personnel.[375] The Director-General of MSF said: "Countries affected to date simply do not have the capacity to manage an outbreak of this size and complexity on their own. I urge the international community to provide this support on the most urgent basis possible."[307]

In late August, MSF called the situation "chaotic" and the medical response "inadequate." They reported that they had expanded their operations, but couldn't keep up with the rapidly increasing need for assistance, which had forced them to reduce the level of care: "It is not currently possible, for example, to administer intravenous treatments." Calling the situation "an emergency within the emergency", MSF reported that many hospitals had shut down due to lack of staff or fears of the virus among patients and staff, which had left people with other health problems without any care at all. Speaking from a remote region, an MSF worker said that a shortage of protective equipment was making the medical management of the disease difficult and that they had limited capacity to safely bury bodies.[376]

By September, treatment for Ebola patients had become unavailable in some areas. Speaking on 12 September, WHO Director-General, Margaret Chan, said: "In the three hardest hit countries, Guinea, Liberia and Sierra Leone, the number of new cases is moving far faster than the capacity to manage them in the Ebola-specific treatment centres. Today, there is not one single bed available for the treatment of an Ebola patient in the entire country of Liberia."[377] According to a WHO report released on 19 September, Sierra Leone was meeting only 35% of its need for patient beds, while for Liberia it was just 20%.[378]

In early December, the WHO reported that at a national level there were enough beds in treatment facilities to treat and isolate all reported Ebola cases, although their uneven distribution was resulting in serious shortfalls in some areas. Similarly, all affected countries had sufficient and widespread capacity to bury reported deaths; however, because not all deaths were reported, it was possible that the reverse could have been the case in some areas. WHO also reported that every district had access to a laboratory to confirm cases of Ebola within 24 hours of sample collection, and that all three countries had reported that more than 80% of registered contacts associated with known cases of Ebola virus disease were being traced, although contact tracing was still a challenge in areas of intense transmission and those with community resistance.[45]

Healthcare settings

Kerry Town Ebola Treatment Centre in Sierra Leone MOD 45158320.jpg at the International Gymnastics Federation

A number of Ebola Treatment Centres were set up in the area, supported by international aid organisations and staffed by a combination of local and international staff. Each treatment centre is divided into a number of distinct and rigorously separate areas. For patients, there is a triage area, and low- and high-risk care wards. For staff, there are areas for preparation and decontamination. An important part of each centre is an arrangement for safe burial or cremation of bodies, required to prevent further infection.[379][380] In January 2015, a new treatment and research centre was built by Rusal and Russia in the city of Kindia in Guinea. It is one of the most modern medical centres in Guinea.[381][382] Also in January, MSF admitted its first patients to a new treatment centre in Kissy, an Ebola hotspot on the outskirts of Freetown, Sierra Leone. The centre has a maternity unit for pregnant women with the virus.[383][384]

Although the WHO does not advise caring for Ebola patients at home, in some cases it became a necessity when no hospital treatment beds were available. For those being treated at home, the WHO advised informing the local public health authority and acquiring appropriate training and equipment.[385][386] UNICEF, USAID and Samaritan's Purse began to take measures to provide support for families that were forced to care for patients at home by supplying caregiver kits intended for interim home-based interventions. The kits included protective clothing, hydration items, medicines, and disinfectant, among other items.[387][388] Even where hospital beds were available, it was debated whether conventional hospitals are the best place to care for Ebola patients, as the risk of spreading the infection is high.[389] In October, the WHO and non-profit partners launched a program in Liberia to move infected people out of their homes into ad hoc centres that could provide rudimentary care.[390] Health facilities with low-quality systems for preventing infection were involved as sites of amplification during viral outbreaks.[391]

Protective clothing[edit]

Examining equipment

The Ebola epidemic caused an increasing demand for protective clothing. A full set of protective clothing includes a suit, goggles, a mask, socks and boots, and an apron. Boots and aprons can be disinfected and reused, but everything else must be destroyed after use. Health workers change garments frequently, discarding gear that has barely been used. This not only takes a great deal of time but also exposes them to the virus because, for those wearing protective clothing, one of the most dangerous moments for contracting Ebola is while suits are being removed.[392]

The protective clothing sets that MSF uses cost about $75 apiece. Staff who have returned from deployments to Western Africa say the clothing is so heavy that it can be worn for only about 40 minutes at a stretch. A physician working in Sierra Leone has said: "After about 30 or 40 minutes, your goggles have fogged up; your socks are completely drenched in sweat. You're just walking in water in your boots. And at that point, you have to exit for your own safety ... Here it takes 20–25 minutes to take off a protective suit and must be done with two trained supervisors who watch every step in a military manner to ensure no mistakes are made, because a slip up can easily occur and of course can be fatal."[305][393] By October, there were reports that protective outfits were beginning to be in short supply and manufacturers began to increase their production,[394] but the need to find better types of suits has also been raised.[395]

USAID published an open competitive bidding for proposals that address the challenge of developing "... new practical and cost-effective solutions to improve infection treatment and control that can be rapidly deployed; 1) to help health care workers provide better care and 2) transform our ability to combat Ebola".[396][397][398] On 12 December 2014, USAID announced the result of the first selection in a press release.[399]

On 17 December 2014, a team at Johns Hopkins University developed a prototype breakaway hazmat suit, and was awarded a grant from the USAID to develop it. The prototype has a small, battery-powered cooling pack on the worker's belt. "You'll have air blowing out that is room temperature but it's 0% humidity ... the Ebola worker is going to feel cold and will be able to function inside the suit without having to change the suit so frequently", said one source.[400] In March, Google developed a tablet that could be cleaned with chlorine; it is charged wirelessly and can transmit information to servers outside the working area.[401][402]

The WHO recommends the use of 2 pairs of gloves, with the outer pair worn over the gown. Using 2 pairs may reduce the risk of sharp injuries; however, there is no evidence that using more than the recommended will give additional protection. WHO also recommends the use of a coverall, which is generally appraised in terms of its resistance to non-enveloped DNA virus. When a gown (or coverall) is worn, it should continue beyond the shoe covers.[403] According to guidelines released by the CDC in August 2015, updates were put in place to improve the PAPR doffing method to make the steps easier, and affirm the importance of cleaning the floor where doffing has been done. Additionally, a designated doffing assistant was recommended to help in this process. The order in which boot covers are removed, by these guidelines, indicates their removal after the coverall or gown. Finally, a trained observer is to read to the healthcare worker each step in donning and doffing, but must not physically assist therein.[404]

CDC staff preparing to enter ETU in Liberia

Healthcare workers[edit]

In the hardest hit areas there have historically been only one or two doctors available to treat 100,000 people, and these doctors are heavily concentrated in urban areas.[308] Ebola patients' healthcare providers, as well as family and friends, are at highest risk of getting infected because they are more likely to come in direct contact with their blood or body fluids. In some places affected by the outbreak, care may have been provided in clinics with limited resources, and workers could be in these areas for several hours with a number of Ebola infected patients.[405] According to the WHO, the high proportion of infected medical staff could be explained by a lack of adequate manpower to manage such a large outbreak, shortages of protective equipment or improper use of what was available, and "the compassion that causes medical staff to work in isolation wards far beyond the number of hours recommended as safe".[308] In August 2014, healthcare workers represented nearly 10 per cent of cases and fatalities—significantly impairing the capacity to respond to an outbreak in an area already facing severe shortages.[406] By 1 July 2015, the WHO reported that a total of 874 health workers had been infected, of which 509 had died.[407]

Among the fatalities was Samuel Brisbane, a former adviser to the Liberian Ministry of Health and Social Welfare, described as "one of Liberia's most high-profile doctors".[408] In July 2014, leading Ebola doctor Sheik Umar Khan from Sierra Leone also died in the outbreak.[119][409][410] In August, a well-known Nigerian physician, Ameyo Adadevoh, died.[411] Mbalu Fonnie, a licensed nurse-midwife and nursing supervisor at the Kenema hospital in Sierra Leone, with over 30 years of experience, died after contracting Ebola while caring for a fellow nurse who was pregnant and had the disease. Fonnie was also a co-author of a study that analysed the genetics of the Ebola virus; five others contracted Ebola and died while working on the same study.[412]

Basing their choice on "the person or persons who most affected the news and our lives, for good or ill, and embodied what was important about the year", the editors of Time magazine in December 2014 named the Ebola health workers as Person of the Year. Editor Nancy Gibbs said: "The rest of the world can sleep at night because a group of men and women are willing to stand and fight. For tireless acts of courage and mercy, for buying the world time to boost its defences, for risking, for persisting, for sacrificing and saving, the Ebola fighters are Time's 2014 Person of the Year."[413] According to an October 2015 report by the CDC, Guinean healthcare workers had 42.2 times higher Ebola infection rates than non-healthcare workers, and male healthcare workers were more affected than their female counterparts. The report indicated that 27% of Ebola infections among healthcare workers in Guinea occurred among doctors. The CDC report also stated that the Guinea Ministry of Health recorded males as representing 46% of the health workforce, and that 67% of Ebola infections among non-doctor healthcare workers occurred among males. The CDC further indicated that healthcare workers in Guinea were less likely to report contact with an infected individual than non-healthcare workers.[414]

Experimental treatments and testing

Further information: Ebola virus disease treatment research

There is as yet no known confirmed medication or treatment for Ebola virus disease. The director of the US National Institute of Allergy and Infectious Diseases 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.[415][416] A number of experimental treatments are undergoing clinical trials.[417][418][419] During the epidemic some patients received experimental blood transfusions from Ebola survivors, but a later study found that the treatment did not provide significant benefit.[420]

The effectiveness of potential treatments for any disease is usually assessed in a randomised controlled trial, which compares the outcome of those who received treatment to those who received a placebo (i.e. dummy treatment). However, randomised controlled trials are considered unethical when a disease is frequently fatal, as is the case with Ebola. In December 2015, a study was released that found that the viral load found in a patient's blood in the week after the onset of symptoms is a strong indication of the patient's likelihood to die or survive the disease. The researchers suggested that this information could help to assess the efficacy of proposed treatments more accurately in non-randomised clinical trials.[421]

Ebola control is hindered by the fact that current diagnostic tests require specialised equipment and highly trained personnel. Since there are few suitable testing centres in Western Africa, this delays diagnosis. As of February 2015 a number of rapid diagnostic tests were under trial.[422] In September 2015, a new chip-based testing method that can detect Ebola accurately was reported. This new device allows for the use of portable instruments that can provide immediate diagnosis.[423][424]

Vaccines

Several Ebola vaccine candidates had been developed in the decade prior to 2014 and had been shown to protect nonhuman primates against infection, but none had yet been approved for clinical use in humans.[425][426][427][428] According to a 2015 review article, about 15 different vaccines were in preclinical stages of development, including DNA vaccines, virus-like particles and viral vectors[429] and another seven as yet unheard-of vaccines were being developed. Additionally, there were two phase III studies being conducted with two different vaccines.[429]

In July 2015, researchers announced that a vaccine trial in Guinea had been completed that appeared to give protection from the virus. The vaccine, rVSV-ZEBOV,[430] had shown high efficacy in individuals, but more conclusive evidence was needed regarding its capacity to protect populations through "herd immunity" . The vaccine trial employed "ring vaccination", a technique that was also used in the 1970s to eradicate smallpox, in which health workers control an outbreak by vaccinating all suspected infected individuals within the surrounding area.[56][57][431][432]

In December 2016, the results of the two-year Guinea trial were published announcing that rVSV-ZEBOV had been found to protect people who had been exposed to cases of Ebola.[31] Of the nearly 6,000 people vaccinated, none had contracted Ebola after a ten-day period while in the group not vaccinated 23 cases developed. In addition to showing high efficacy among those vaccinated, the trial also showed that unvaccinated people were indirectly protected from Ebola virus through the ring vaccination approach, termed "herd immunity". The vaccine has not yet had regulatory approval, but it is considered to be so effective that 300,000 doses have already been stockpiled. Researchers have found the results "quite encouraging [but] there is still a lot more work to be done on vaccines for Ebola." Not yet known is the length of time that a vaccination will be effective and whether it will prove effective for the Sudan virus rather than only EBOV, which is responsible for the Western Africa outbreak.[32][433] In April 2018 rVSV-ZEBOV Ebola vaccine was used to stop an outbreak for the first time, the 2018 Équateur province Democratic Republic of the Congo Ebola virus outbreak, with 3,481 people vaccinated.[434] rVSV-ZEBOV received regulatory approval in 2019.[33][34]

Outlook

From the beginning of the outbreak, there existed considerable difficulty in getting reliable estimates—both of the number of people affected and of its geographical extent.[435] The three most affected countries—Guinea, Liberia and Sierra Leone—are among the poorest in the world, with extremely low levels of literacy, few hospitals or doctors, low-quality physical infrastructure, and weakly functioning government institutions.[436] One study yielded results of the spatio-temporal evolution of the viral outbreak. With the use of heat maps, it was determined that the outbreak did not uniformly unfold over the affected community areas. Growth in the regions of Guinea, Liberia and Sierra Leone was very different over time, indicating that monitoring the outbreak at district level was important. Visual inspection of incidence curves alone could not render the needed results or data; growth rates with a two-dimensional heat map were used. Finally, the study showed that accurate predictions of growth were improbable, coupled with knowledge about the disease that was not fully adequate at the time (as there were now cases of sexual transmission).[437]

Statistical measures

Calculating the case fatality rate (CFR) accurately is difficult in an ongoing epidemic due to differences in testing policies, the inclusion of probable and suspected cases, and the inclusion of new cases that have not run their course. In August 2014, the WHO made an initial CFR estimate of 53%, though this included suspected cases.[438][439] In September and December 2014, the WHO released revised and more accurate CFR figures of 70.8% and 71% respectively, using data from patients with definitive clinical outcomes.[12][20][18] The CFR among hospitalised patients, based on the three intense-transmission countries, was between 57% and 59% in January 2015.[359]

Mortality is measured by number of deaths in a population per the proportion of the population per unit of time.[440]

The basic reproduction number, R0, is a statistical measure of the average number of people infected by a single infectious individual in a population with no prior immunity. If the basic reproduction number is less than 1, the epidemic will die out; if it is greater than 1, the epidemic will continues to spread—with exponential growth in the number of cases.[441] In September 2014, the estimated values of R0 were 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone.[12][442][443] In October 2014, the WHO noted that exponential increase of cases continued in the three countries with the most intense transmission.[444]

Projections of future cases

On 28 August 2014, the WHO released its first estimate of the possible total cases from the outbreak as part of its road map for stopping the transmission of the virus. It stated that "this Roadmap assumes that in many areas of intense transmission the actual number of cases may be two- to fourfold higher than that currently reported. It acknowledges that the aggregate case load of Ebola could exceed 20,000 over the course of this emergency. The Roadmap assumes that a rapid escalation of the complementary strategies in intense transmission, resource-constrained areas will allow the comprehensive application of more standard containment strategies within three months." The report included an assumption that some country or countries would pay the required cost of their plan, estimated at half a billion US dollars.[310]

When the WHO released these estimates, a number of epidemiologists presented data to show that the WHO projection of a total of 20,000 cases was likely an underestimate.[445][446] On 9 September, Jonas Schmidt-Chanasit of the Bernhard Nocht Institute for Tropical Medicine in Germany, controversially announced that the containment fight in Sierra Leone and Liberia had already been "lost" and that the disease would "burn itself out".[447]

On 23 September 2014, the WHO revised their previous projection, stating that they expected the number of Ebola cases in Western Africa to be in excess of 20,000 by 2 November 2014.[12] They further stated, that if the disease was not adequately contained it could become native in Guinea, Sierra Leone and Liberia, "spreading as routinely as malaria or the flu",[448] and according to an editorial in the New England Journal of Medicine, eventually to other parts of Africa and beyond.[449]

In a report released on 23 September 2014, the CDC analysed the impact of under-reporting, which required correction of case numbers by a factor of up to 2.5. With this correction factor, approximately 21,000 total cases were estimated for the end of September 2014 in Liberia and Sierra Leone alone. The same report predicted that total cases, including unreported cases, could reach 1.4 million in Liberia and Sierra Leone by the end of January 2015 if no improvement in intervention or community behaviour occurred.[23] However, at a congressional hearing on 19 November, the Director of the CDC said that the number of Ebola cases was no longer expected to exceed 1 million, moving away from the worst-case scenario that had been previously predicted.[450]

A study published in December 2014 found that transmission of the Ebola virus occurs principally within families, in hospitals and at funerals. The data, gathered during three weeks of contact tracing in August, showed that the third person in any transmission chain often knew both the first and second person. The authors estimated that between 17% and 70% of cases in Western Africa were unreported—far fewer than had been estimated in prior projections. The study concluded that the epidemic would not be as difficult to control as feared, if rapid, vigorous contact tracing and quarantines were employed.[451]

Projections of future cases should also reflect the possibility that deforestation might have a hand in terms of the more recent Ebola outbreaks. It has been suggested that due to the clearing of forest for commercial use, various types of bats namely fruit bats may be taken out of their natural habitat and therefore into closer and potential contact with civilisation.[291][290]

Economic effects

UNDG, improves efficiency in needing countries

In addition to the loss of life, the outbreak had a number of significant economic impacts. In March 2015, the United Nations Development Group reported that due to a decrease in trade, closing of borders, flight cancellations, and drop in foreign investment and tourism activity fuelled by stigma, the epidemic resulted in vast economic consequences both in the affected areas and throughout Africa.[50] A September 2014 report in the Financial Times suggested that the economic impact of the Ebola outbreak could kill more people than the disease itself.[452]

With regard to Ebola and economic activity in the country of Liberia, a study found that 8% of automotive firms, 8% of construction firms, 15% of food businesses and 30% of restaurants had closed due to the Ebola outbreak. Montserrado county experienced up to 20% firm closure. This indicated a decline in the Liberian national economy during the outbreak, as well as an indication that the county of Montserrado was hardest hit economically. The capital city Monrovia suffered construction and restaurant unemployment the most, while outside the capital, the food and beverage sectors suffered economically. A recuperation in the economy, at the end of the outbreak, was expected to be more rapid in some sectors than in others. Also, if the massive decline in economic activity persisted, the authors suggested a focus on economic recovery in addition to support for the healthcare system. The World Bank had projected an estimated loss of $1.6 billion in productivity for all three affected Western African countries combined for 2015. In Liberian counties that were less affected by the outbreak, the number of individuals employed fell by 24%. Montserrado saw a 47% decline in employment per firm in contrast to what was obtained prior to the Ebola outbreak.[453]

Another study showed that the economic effect of the Ebola outbreak would be felt for years due to preexisting social vulnerability. The economic effects were being felt nationwide in Liberia, such as the termination of expansions in the mining business. Initial scenarios had placed expected economic losses at $25 billion; however subsequent World Bank estimates were much lower, at about 12% of the combined GDP of the 3 worst hit countries.[454] The authors went on to state that social vulnerability has multiple factors and proposed a classification based on multiple variables instead of single indicators such as food insecurity or lack of hospitals, which were problems faced by rural Liberians. In spite of the end of civil violence since 2003 and inflows from international donors, the reconstruction of Liberia had been very slow and non-productive—water delivery systems, sanitation facilities and centralised electricity were practically non-existent, even in Monrovia. Even before the outbreak, medical facilities did not have potable water, lighting or refrigeration. The authors indicated that lack of food and other economic effects would probably continue in the rural population long after the Ebola outbreak had ended.[454]

Other economic impacts were as follows:

  • In August 2014 it was reported that many airlines had suspended flights to the area.[455] Markets and shops had closed due to travel restrictions, a cordon sanitaire, or fear of human contact, which led to loss of income for producers and traders.[456]

  • Movement of people away from affected areas disturbed agricultural activities.[457][458] The FAO warned that the outbreak could endanger harvests and food security in Western Africa,[459] and that with all the quarantines and movement limitations placed on them, more than 1 million people could be food insecure by March 2015.[460] By 29 July, the World Bank had given 10,500 tons of maize and rice seed to the 3 hardest-hit countries to help them to rebuild their agricultural systems.[461]

  • Tourism was directly impacted in the affected countries.[462] In April 2014, Nigeria reported that 75% of hotel business had been lost due to fears of the outbreak;[463] the limited Ebola outbreak had cost that country 8 billion.[464] Other African countries that were not directly affected by the virus also reported adverse effects on tourism.[465][466][467] For example, in 2015, it was reported that Gambia's tourism had fallen below 50 per cent of its normal business during the same period the prior year,[468][469] Elmina Bay in Ghana had an 80% decrease in US tourism,[470] and Kenya,[471] Zimbabwe,[472] Senegal, Zambia, and Tanzania also reported a drop.[473]

  • Some foreign mining companies withdrew all non-essential personnel, deferred new investment, and cut back operations.[458][474][475] In December 2014, it was reported that the iron ore mining company, African Minerals, had started the shutdown of its Sierra Leone operations because it was running low on income.[476] In March 2015, it was reported that Sierra Leone had begun to diversify away from mining, due to the country's recent problems.[477]

In January 2015, Oxfam, a UK-based disaster relief organisation, indicated that a "Marshall Plan" (a reference to the massive plan to rebuild Europe after World War II) was needed so that countries could begin to financially assist those that had been worst hit by the virus.[478] The call was repeated in April 2015 when the most-affected Western African countries asked for an $8 billion "Marshall Plan" to rebuild their economies. Speaking at the World Bank and the International Monetary Fund (IMF), Liberian president Ellen Johnson Sirleaf said the amount was needed because "[o]ur health systems collapsed, investors left our countries, revenues declined and spending increased."[479]

The IMF has been criticised for its lack of assistance in the efforts to combat the epidemic. In December 2014, a Cambridge University study linked IMF policies with the financial difficulties that prevented a strong Ebola response in the three most heavily affected countries,[480] and they were urged by both the UN and NGOs who had worked in the affected countries to grant debt relief rather than low-interest loans. According to one advocacy group, "... yet the IMF, which has made a $9 billion surplus from its lending over the last three years, is considering offering loans, not debt relief and grants, in response".[481][482] On 30 January 2015, the IMF reported it was close to reaching a deal on debt forgiveness.[483] On 22 December, it was reported that the IMF had given Liberia an additional $10 million due to the economic impact of the Ebola virus outbreak.[484]

In October 2014, a World Bank report estimated overall economic impacts of between $3.8 billion and $32.6 billion, depending on the extent of the outbreak and speed of containment. It expected the most severe losses in the three affected countries, with a wider impact across the broader Western African region.[485][486] On 13 April 2015, the World Bank said that they would soon announce a major new effort to rebuild the economies of the three hardest-hit countries.[487] On 23 July, a World Bank poll warned that "we are not ready for another Ebola outbreak".[488] On 15 December, the World Bank indicated that by 1 December 2015, it had marshalled $1.62 billion in financing for the Ebola outbreak response.[489]

On 6 July 2015, UN Secretary-General Ban Ki-moon announced that he would host an Ebola recovery conference to raise funds for reconstruction, stating that the three countries hardest hit by Ebola needed about $700 million to rebuild their health services over a two-year period.[490] On 10 July, it was announced that the countries most affected by the Ebola epidemic would receive $3.4 billion to rebuild their economies.[491][492] On 29 September, the leaders of both Sierra Leone and Liberia indicated at the UN General Assembly the launch of a "Post-Ebola Economic Stabilization and Recovery Plan".[493] On 24 November, it was reported that due to the decrease in commodity prices and the Western African Ebola epidemic, China's investment in the continent had declined 43% in the first 6 months of 2015.[494] On 25 January, the IMF projected a GDP growth of 0.3% for Liberia, that country indicating it would cut spending by 11 per cent due to a stagnation in the mining sector, which would cause a domestic revenues drop of $57 million.[495]

Responses

Further information: Responses to the Ebola virus epidemic in West Africa

In July 2014, the WHO convened an emergency meeting of health ministers from eleven countries and announced collaboration on a strategy to co-ordinate technical support to combat the epidemic. In August they published a road map to guide and coordinate the international response to the outbreak, aiming to stop ongoing Ebola transmission worldwide within 6–9 months, and formally designated the outbreak as a Public Health Emergency of International Concern.[47] This is a legal designation used only twice before (for the 2009 H1N1 (swine flu) pandemic and the 2014 resurgence of poliomyelitis) that invokes legal measures on disease prevention, surveillance, control, and response, by 194 signatory countries.[496][497]

In September 2014, the United Nations Security Council declared the Ebola virus outbreak in Western Africa "a threat to international peace and security" and unanimously adopted a resolution urging UN member states to provide more resources to fight the outbreak.[498][499] In October, WHO and the UN Mission for Ebola Emergency Response announced a comprehensive 90-day plan to control and reverse the Ebola epidemic. The ultimate goal was to have capacity in place for the isolation of 100% of Ebola cases and the safe burial of 100% of casualties by 1 January 2015 (the 90-day target).[500] Many nations and charitable organisations cooperated to realise the plan,[501] and a WHO situation report published mid-December indicated that the international community was on track to meet the 90-day target.[502]

In May 2015, Dr Margaret Chan indicated, "demands on WHO were more than ten times greater than ever experienced in the almost 70-year history of this Organization"[503][504] and on 23 March, she stated that "the world remains woefully ill-prepared to respond to outbreaks that are both severe and sustained."[505]

Criticism of WHO

There was significant criticism of the WHO from some aid agencies because its response was perceived as slow and insufficient, especially during the early stages of the outbreak.[46][506] In October 2014, the Associated Press reported in an internal draft document that the WHO admitted "nearly everyone" involved in the Ebola response failed to notice factors that turned the outbreak into the largest on record, and that they had missed chances to stop the spread of Ebola due to "incompetent staff, bureaucracy and a lack of reliable information".[507] Peter Piot, co-discoverer of the Ebola virus, called the WHO regional office in Africa "really not competent."[508] In April 2015, the WHO admitted very serious failings in handling the crisis and indicated reforms for any future crises; "we did not work effectively in coordination with other partners, there were shortcomings in risk communications and there was confusion of roles and responsibilities".[509] The Ebola crisis was discussed at the June 2015 G7 meeting. The leaders pledged to assist in carrying out WHO regulations. Critics criticised the G7 leaders, saying they were not committed enough in the fight against the possibility of future pandemics.[510][511]

In 2015 a panel of experts looked at the ways of preventing small outbreaks from becoming large epidemics. Their recommendations were published in the November issue of The Lancet. According to the panel, the epidemic had exposed problems in the national (and international) institutions responsible for protecting the public from the human consequences of infectious disease outbreaks such as the Ebola epidemic. The panel was highly critical of the WHO's management of the Ebola crisis noting that it took them months to respond and when they did they were slow to act, poorly co-ordinated and inadequately informed. The report pointed out that the committee responsible for checking the WHO's actions during the outbreak (i.e. the WHO Ebola Interim Assessment Panel) had delayed responses due to worries about political resistance from the Western African leaders, economic consequences, and a system within the WHO that discouraged open debate about issues such as emergency declarations. The WHO may also have hesitated because it was criticised for creating panic by declaring a public health emergency during the relatively mild 2009 H1N1 pandemic. This, the report states, showed the risks in having such consequential decision-making power in one individual—a risk made worse when there was no mechanism of responsibility for such leadership failure.[512][513][514]

The panel outlined 10 recommendations for the prevention and handling of future infectious disease outbreaks. Included in the recommendations of the changes needed to fight future outbreaks is the creation of a U.N. Security Council health committee to expedite political attention to health issues and the establishment of a global fund to finance and accelerate the development of outbreak-relevant drugs and treatment. The report also noted that competent governance of the global system demanded political leadership and a WHO that is more focused and appropriately financed and whose integrity is restored through the application of adequate reforms and leadership.[512]

The WHO also came under fire for refusing to send Dr. Olivet Buck to Germany for experimental treatment after she contracted Ebola per the government of Sierra Leone's request. WHO claimed they could only evacuate medical professionals they had deployed to the region, not locals. Dr. Olivet Buck was the Medical Superintendent at Lumley Government Hospital in Freetown, Sierra Leone. It's believed that she contracted the virus while continuing to treat patients even during a shortage of personal protective equipment. Her loyalty and dedication to her community never wavered.[515]

Image of table : [HK00AC][GDrive]


2014 (Oct 16) - St. Louis Post-Dispatch

https://www.newspapers.com/image/148544855/?terms=liberia%20chimpanzee&match=1

2014-10-16-st-louis-post-dispatch-pg-a19

2014-10-16-st-louis-post-dispatch-pg-a19-clip-ebola-2

Mentioned : Dr. Sharon Lynn Deem (born 1963)

2014 (Oct 27) - The New Yorker : "The Ebola Wars - How genomics research can help contain the outbreak." By Richard Preston

PDF of source : [HP00BT][GDrive]

Image : Pardis Sabeti and Stephen Gire in the Genomics Platform of the Broad Institute of M.I.T. and Harvard, in Cambridge, Massachusetts. They have been working to sequence Ebola’s genome and track its mutations. Photograph by Dan Winters[HP00BU][GDrive]

The most dangerous outbreak of an emerging infectious disease since the appearance of H.I.V., in the early nineteen-eighties, seems to have begun on December 6, 2013, in the village of Meliandou, in Guinea, in West Africa, with the death of a two-year-old boy who was suffering from diarrhea and a fever. We now know that he was infected with Ebola virus. The virus is a parasite that lives, normally, in some as yet unidentified creature in the ecosystems of equatorial Africa. This creature is the natural host of Ebola; it could be a type of fruit bat, or some small animal that lives on the body of a bat—possibly a bloodsucking insect, a tick, or a mite.

Before now, Ebola had caused a number of small, vicious outbreaks in central and eastern Africa. Doctors and other health workers were able to control the outbreaks quickly, and a belief developed in the medical and scientific communities that Ebola was not much of a threat. The virus is spread only through direct contact with blood and bodily fluids, and it didn’t seem to be mutating in any significant way.

After Ebola infected the boy, it went from him to his mother, who died, to his three-year-old sister, who died, and to their grandmother, who died, and then it left the village and began moving through the human population of Guinea, Liberia, and Sierra Leone. Since there is no vaccine against or cure for the disease caused by Ebola virus, the only way to stop it is to break the chains of infection. Health workers must identify people who are infected and isolate them, then monitor everybody with whom those people have come in contact, to make sure the virus doesn’t jump to somebody else and start a new chain. Doctors and other health workers in West Africa have lost track of the chains. Too many people are sick, and more than two hundred medical workers have died. Health authorities in Europe and the United States seem equipped to prevent Ebola from starting uncontrolled chains of infection in those regions, but they worry about what could happen if Ebola got into a city like Lagos, in Nigeria, or Kolkata, in India. The number of people who are currently sick with Ebola is unknown, but almost nine thousand cases, including forty-five hundred deaths, have been reported so far, with the number of cases doubling about every three weeks. The virus seems to have gone far beyond the threshold of outbreak and ignited an epidemic.

The virus is extremely infectious. Experiments suggest that if one particle of Ebola enters a person’s bloodstream it can cause a fatal infection. This may explain why many of the medical workers who came down with Ebola couldn’t remember making any mistakes that might have exposed them. One common route of entry is thought to be the wet membrane on the inner surface of the eyelid, which a person might touch with a contaminated fingertip. The virus is believed to be transmitted, in particular, through contact with sweat and blood, which contain high concentrations of Ebola particles. People with Ebola sweat profusely, and in some instances they have internal hemorrhages, along with effusions of vomit and diarrhea containing blood.

Despite its ferocity in humans, Ebola is a life-form of mysterious simplicity. A particle of Ebola is made of only six structural proteins, locked together to become an object that resembles a strand of cooked spaghetti. An Ebola particle is only around eighty nanometres wide and a thousand nanometres long. If it were the size of a piece of spaghetti, then a human hair would be about twelve feet in diameter and would resemble the trunk of a giant redwood tree.

Once an Ebola particle enters the bloodstream, it drifts until it sticks to a cell. The particle is pulled inside the cell, where it takes control of the cell’s machinery and causes the cell to start making copies of it. Most viruses use the cells of specific tissues to copy themselves. For example, many cold viruses replicate in the sinuses and the throat. Ebola attacks many of the tissues of the body at once, except for the skeletal muscles and the bones. It has a special affinity for the cells lining the blood vessels, particularly in the liver. After about eighteen hours, the infected cell is releasing thousands of new Ebola particles, which sprout from the cell in threads, until the cell has the appearance of a ball of tangled yarn. The particles detach and are carried through the bloodstream, and begin attaching themselves to more cells, everywhere in the body. The infected cells begin spewing out vast numbers of Ebola particles, which infect more cells, until the virus reaches a crescendo of amplification. The infected cells die, which leads to the destruction of tissues throughout the body. This may account for the extreme pain that Ebola victims experience. Multiple organs fail, and the patient goes into a sudden, steep decline that ends in death. In a fatal case, a droplet of blood the size of the “o” in this text could easily contain a hundred million particles of Ebola virus.

Inside each Ebola particle is a tube made of coiled proteins, which runs the length of the particle, like an inner sleeve. Viewed with an electron microscope, the sleeve has a knurled look. Like the rest of the particle, the sleeve has been shaped by the forces of natural selection working over long stretches of time. Ebola is a filovirus, and filoviruses appear to have been around in some form for millions of years. Within the inner sleeve of an Ebola particle, invisible even to a powerful microscope, is a strand of RNA, the molecule that contains the virus’s genetic code, or genome. The code is contained in nucleotide bases, or letters, of the RNA. These letters, ordered in their proper sequence, make up the complete set of instructions that enables the virus to make copies of itself. A sample of the Ebola now raging in West Africa has, by recent count, 18,959 letters of code in its genome; this is a small genome, by the measure of living things. Viruses like Ebola, which use RNA for their genetic code, are prone to making errors in the code as they multiply; these are called mutations. Right now, the virus’s code is changing. As Ebola enters a deepening relationship with the human species, the question of how it is mutating has significance for every person on earth.

The Kenema Government Hospital, in Kenema, Sierra Leone, is a scatter of low yellow-and-red-painted cinder-block buildings with rusty metal roofs. It spreads down a hillside near the center of town, and, according to medical workers there, is normally bustling with patients and their families. The town sits in fertile, hilly country, dotted with small villages, ninety miles southwest of the place where the borders of Sierra Leone, Guinea, and Liberia converge in a triskelion. This border area was the cradle of the Ebola outbreak. For decades, the Kenema hospital has had a special twelve-bed unit called the Lassa Fever Ward and Research Program. Lassa fever is caused by Lassa virus, which is classified by virologists as a Biosafety Level 4 pathogen—lethal, infectious, typically with no vaccine and no reliable cure. In May of this year, the chief physician of the Lassa program, Sheik Humarr Khan, was watching out for Ebola, which, like Lassa, is a Level 4 pathogen. The virus had been spreading in Guinea and Liberia, but there had been no reported cases yet in Sierra Leone.

Around May 23rd, a woman who was having a miscarriage arrived at the hospital. She tested negative for Lassa, but Khan suspected that she might have Ebola. As it turned out, she had been at the funeral of a faith healer who had recently been to Guinea and had died after attempting to heal a number of people sick with Ebola. Khan ordered a blood sample to be taken from her, and he isolated her in the hospital’s Lassa ward. Khan was a specialist in viral hemorrhagic diseases and one of the world’s leading experts in Lassa fever, and people described him as voluble and intense; virus experts from a number of American research institutions had developed close friendships with him and his staff. He devoted much of his time to tending patients at the hospital, who were typically poor. Quite a few of them couldn’t afford to buy medicine, so Khan bought it for them, and he gave them food if they looked hungry. “You must eat or you cannot get better,” he told them.

“I still compose my tweets in longhand on a yellow legal pad.”

When Khan was with patients in the Lassa ward, he wore a type of biohazard outfit known as personal protective equipment, or P.P.E. At Kenema, the outfit consisted of a full-body suit and head covering made of white Tyvek fabric, a breathing mask, a plastic face shield and goggles, two pairs of surgical gloves, one pair of rubber gloves, rubber boots, and a plastic apron. Patients with Lassa had seizures and hemorrhages and went into comas, and many of them died, despite excellent care. In the evening, Khan liked to watch soccer games on television with friends, and when he got tired on his rounds he would sit in a plastic chair for a moment, chatting with people as he drank a can of Sprite.

The day after the woman who had miscarried was admitted to the Lassa unit, a lab technician put on P.P.E., carried a sample of the woman’s blood into the lab, and tested it. It was positive for Ebola. Wanting to be sure, the technician e-mailed the test results to the lab of an associate professor of biology at Harvard University named Pardis Sabeti. Over the years, Sabeti had forged ties with the Lassa program, and had become friends with Khan.

Sabeti is a slender woman in her late thirties, with a warm manner. She is the head of a lab at Harvard, and leads viral-genome efforts at the Broad Institute of M.I.T. and Harvard. She specializes in reading and analyzing the genomes of organisms and, in particular, studies virus evolution—the way viruses change over time as they adapt to their environments. In her spare time, Sabeti is the lead singer and songwriter for an indie band called Thousand Days. Its fourth album has been delayed owing to her work on the Ebola outbreak.

When Sabeti learned that Ebola had reached Sierra Leone, she called a meeting in what she and her colleagues had begun to refer to as the Ebola War Room. It is a sunlit room with a large table at the Broad Institute, on the M.I.T. campus. As the outbreak gathered strength, Sabeti became the de-facto head of a team of scientists who met regularly in the War Room to plan and direct elements of the human defense against Ebola. They had sent team members with advanced diagnostic equipment to Kenema and to Nigeria, to help doctors diagnose Ebola quickly. “The faster you can get a diagnosis of Ebola, the faster you can stop it,” Sabeti said recently. “But the big question is, how is this thing going to be stopped?”

Sabeti and her team made plans to begin reading the genome of the virus as soon as possible. All the drugs, vaccines, and diagnostic tests for Ebola depend critically on the virus’s genetic code. The researchers knew that the code was changing. Could Ebola be evolving away from the defenses against it? Where had it come from? Had it started in one person or had it begun in different people at different times and places? Could Ebola become more contagious, and spread faster?

Sabeti and her team conceived a plan to obtain samples of blood from people infected with Ebola. They would read the genomes of whatever Ebola they could find in the patients’ blood. When monks copied texts by hand in the Middle Ages, they made mistakes. Since Ebola makes errors as it replicates, each genome was like a hand-copied text, and detectable differences would emerge among the genomes; there isn’t just one “strain” of the virus. Ebola is not a thing but a swarm. It is a vast population of particles, different from one another, each particle competing with the others for a chance to get inside a cell and copy itself. The swarm’s genetic code shifts in response to the changing environment. By looking at a few genomes of Ebola, the scientists hoped to grasp an image of the whole virus, which could be conceived of as a life-form visible in four dimensions, as vast amounts of code flowing through time and space. To find the genome, they needed blood.

Teams of epidemiologists and health workers spread out from Kenema and identified twelve more women who were sick with Ebola. All of them had been at the funeral of the faith healer. They were taken to the Kenema hospital and placed in the Lassa ward. Humarr Khan and top officials at the Sierra Leone Ministry of Health were anxious to have the genome of Ebola sequenced, and so Khan and Sabeti, working with the ministry officials, used a method of collecting blood that didn’t interfere with patient care: the researchers scavenged samples of blood serum from tubes left over from clinical care. This material was biohazardous medical waste, intended to be burned in the hospital’s incinerator. “We did everything we could to make no footprint in the way we took samples,” Sabeti said. Blood samples were also taken from thirty-five other people who were suspected of having been exposed to Ebola.

The result was a large number of microtubes of human blood serum collected from forty-nine people. Each microtube was the size of the sharpened end of a pencil and contained a droplet of human blood serum, golden in color and no bigger than a lemon seed. The droplets were mixed with a larger quantity of a sterilizing chemical that kills Ebola. Augustine Goba, the head of the hospital lab, packed the tiny tubes of sterilized blood serum in ice inside a box, then sent the box by DHL Express to Harvard.

Four days later, on June 4th, the box arrived at Sabeti’s lab, where a research scientist named Stephen Gire put on bioprotective gear and carried the box into a tiny biocontainment lab to open it. The samples were supposed to be safe, but Gire was taking no chances. Gire is tall and quiet, and there is an air of precision about him. He is a talented chef, and in 2008 he was offered a chance to compete for a spot on the television show “Top Chef,” but he turned it down and, instead, went to the Democratic Republic of the Congo to set up a lab and study monkeypox, a virus related to smallpox. On Gire’s left forearm is a tattoo showing a particle of monkeypox, a stylish image of the virus’s inner structure that Gire designed himself, and which looks like a nest of crescent moons. Now, in the lab at Harvard with the unopened box of blood samples from Africa, he realized that he had forgotten to bring along a knife. He fished out his car keys, slit open the box, and removed the microtubes. The ice had melted, but the tubes were still cold, and they were visibly safe: the color in the tubes confirmed that the blood serum had been sterilized. Each tube contained around a billion particles of Ebola virus.

Gire’s first job was to extract from the blood serum the virus’s genetic material. Gire tested all the samples for the presence of Ebola virus. Of the forty-nine people whose blood samples were in the tubes, fourteen had been infected with Ebola. He could tell just by looking: in those samples, the virus had damaged the blood, and the serum had a murky look, clouded with dead red blood cells. He worked late, spinning all the tubes in a centrifuge and adding chemicals. When he was finished, he had fourteen small, clear droplets of water solution, each in its own tube. In each droplet were vast numbers of broken strands of RNA—shattered fragments of genetic code of the Ebola that had once drifted in the blood of the fourteen people from around Kenema. There were many different genomes in the tubes, for the virus had likely mutated as it multiplied.

The next morning, Gire took a car to the M.I.T. campus, carrying a small box containing the tubes of droplets with the Ebola RNA. There, in a lab at the Broad Institute, he and a colleague named Sarah Winnicki, working alongside two other research teams, prepared the RNA to be decoded. The work took four days, and Gire and Winnicki hardly slept. By the end, they had combined all fourteen samples into a single, crystal-clear droplet of water solution. The drop contained about six trillion snippets of DNA. Each was a mirror image of a piece of RNA from the blood samples. Most of the snippets were human genetic code, but among them were about two hundred billion snippets of code from Ebola. There were also many billions of fragments of code from bacteria and other viruses—from anything that happened to be living in the blood. This droplet was referred to as a library.

“I’m so ready to quit—the pay sucks, and every night I go home reeking of hazelnut.”

Each piece of DNA in the droplet had been tagged with a unique bar code—a short combination of eight letters of DNA code—identifying that particular fragment as having come from one of the fourteen patients. “You could consider each bar-coded fragment of DNA as a kind of book,” Gire said. “The book is bound in covers and has an I.S.B.N. number on it. It’s a short book, so a reader can easily digest it. You can find the book by its I.S.B.N. number, and that’s why the droplet is called a library. The books in the DNA library are bound so that the library can be put in a machine”—a genetic sequencer—“and the machine reads all the books.” The droplet contained many more books of DNA letters than there are books in the Library of Congress. The books were all sitting in one immense, jumbled pile, and what was between their covers was unknown.

On Friday, June 13th, Gire carried a single microtube containing the liquid-droplet library to a logging station in the Genomics Platform of the Broad Institute. The Platform houses a suite of rooms crowded with DNA-sequencing machines. Each machine is a white rectangular box about the size of a chest freezer and costs a million dollars; there are more than fifty of them in the Platform, lined up in rows. Half a dozen technicians tend them around the clock, as they read letters of DNA gathered from biological samples. Recently, the machines have read the genomes of the rabbit, the coelacanth, the malaria parasite, the mosquito that carries malaria, candida fungus, Epstein-Barr virus, and a number of human genes involved in cancer, autism, and schizophrenia.

Using a pipette, a technician sucked up about a tenth of Gire’s Ebola droplet—an amount like a fleck of moisture on a wet day—and placed it on a glass slide known as a flow cell. The fleck of liquid contained the full library of code from the blood of the fourteen Ebola patients. The bit of water spread into channels on the flow cell, which sat in the mouth of an Illumina HiSeq 2500 machine, one of the fastest DNA sequencers in the world.

For the next twenty-four hours, the sequencer worked automatically, pulsing liquids across the flow cell, while lasers shone on it. On the surface of the flow cell, hundreds of millions of fragments of DNA had gathered into hundreds of millions of microscopic colored spots. The colors of the individual spots were changing as the process went on, and a camera took pictures of the changing field of spots and stored the data. Twenty-four hours later, the machine had finished reading Gire’s library of bar-coded fragments of DNA. The data were sent to the Broad Institute’s computer arrays, which assembled all the fragments into finished genetic code—it organized the vast pile of books in the library and placed the letters of all the books in their proper order on shelves. On Sunday, June 15th, Gire and Sabeti got word that the computers had finished their job. The result was twelve full genomes of Ebola virus—the Ebolas that had lived in twelve of the fourteen people. (The computers had not been able to assemble the Ebola genomes from two of the people.) Sabeti and her team started the work of analyzing the code, to see how Ebola was changing.

In early July, Stephen Gire flew to Sierra Leone with another member of Sabeti’s team, and they went to the Kenema hospital, bringing with them lab equipment for use in the Ebola outbreak. Gire was grieved by what he saw. Ebola patients were flowing in from the countryside, dying and terrified. They had filled up the Lassa ward, which had become an Ebola ward, and a second ward—a large white structure with plastic walls and a plastic roof—had been erected. It was full of Ebola patients. The new ward had a plastic viewing window in it, so that people could see and talk to their loved ones inside the ward. Family members of Ebola patients were milling around the window. As Gire recalled, there were shouts of surprise and joy when a patient came to the window and family members saw that the patient was alive and could walk, and cries of sorrow when news came that someone had died. Some in the crowd were silent, baffled by the white building and the moonsuits worn by the health workers. In that part of the world, not everybody believed in the infectious theory of disease, the idea that illnesses can spread through microbes. Why wouldn’t the doctors let people see or touch their loved ones at a funeral? Many people distrusted the government, and spiritual explanations for the disease circulated.

Humarr Khan was working in the Ebola wards. When he came out, and had stripped off his P.P.E., Gire thought that he seemed exhausted and tense. Khan met regularly with international aid workers, and he made countless calls on his cell phone to representatives from the World Health Organization and officials from the Sierra Leone Ministry of Health, pleading for more help, more resources. He called family members—he had nine brothers and sisters, some of whom lived in the United States, and his parents were still alive, in Lungi, a town not far from Freetown, the capital. He spoke with Pardis Sabeti; he planned to join her group at Harvard in a few months. He was fascinated by genomics and he wanted to know how the sequencing of Ebola was going. He couldn’t stand the bureaucracy of the outbreak, Sabeti told me, and he would return to the Ebola wards as if they were a refuge from trouble. He seemed more at ease wearing P.P.E. and caring for patients.

Khan had been running the Lassa program for almost a decade. In 2004, his predecessor, Aniru Conteh, accidentally pricked himself with a needle contaminated with blood from a pregnant woman who had Lassa. Conteh died twelve days later, of Lassa fever, tended by his own nurses. For months, the government couldn’t find any doctor willing to run the Lassa program. Khan, who had just finished his internship at the Sierra Leone College of Medicine, agreed to take the job.

Khan arrived driving a battered old car. He was thirty, a modest, handsome man who smiled and joked playfully with people. Khan took up his work and gave patients exceptional attention. One day, a U.S. graduate student named Joseph Fair fell desperately ill with bloody diarrhea. Khan paid a visit to Fair at his room in a nearby Catholic mission, and that was when Fair discovered that Khan had a beautiful bedside manner. After prescribing antibiotics, Khan jovially said to him, “You’ll be fine.” But, leaving the room, Khan forgot to close the door. Moments later, Fair heard him blurt out to somebody, “This guy is dying! I can’t have an expat die on me!” Fair got better, and he and Khan soon became friends. A few years later, they were having a beer in a bar in New Orleans when Fair told Khan that the first time they met he had heard Khan say he was dying. “Well, you were dying,” Khan answered. Fair said, “You didn’t tell me.” Khan burst out laughing. “I would say you were dying? You were my patient. Can you imagine?”

Khan worked long hours in the Ebola wards, trying to reassure patients. Then one of the nurses got sick with Ebola and died. She hadn’t even been working in the Ebola ward. The virus particles were invisible, and there were astronomical numbers of them in the wards; they were all over the floor and all over the patients.

There are two distinct ways a virus can travel in the air. In what’s known as droplet infection, the virus can travel inside droplets of fluid released into the air when, for example, a person coughs. The droplets travel only a few feet and soon fall to the ground. The other way a virus can go into the air is through what is called airborne transmission. In this mode, the virus is carried aloft in tiny droplets that dry out, leaving dust motes, which can float long distances, can remain infective for hours or days, and can be inhaled into the lungs. Particles of measles virus can do this, and have been observed to travel half the length of an enclosed football stadium. Ebola may well be able to infect people through droplets, but there’s no evidence that it infects people by drying out or getting into the lungs on dust particles. In 1989, a virus known today as Reston, which is a filovirus related to Ebola, erupted in a building full of monkeys in Reston, Virginia, and travelled from cage to cage. One possible way, never proved, is that the virus particles hitched rides in mist driven into the air by high-pressure spray hoses used to clean the cages, and then circulated in the building’s air system. A rule of thumb among Ebola experts is that, if you are not wearing biohazard gear, you should stand at least six feet away from an Ebola patient, as a precaution against flying droplets.

Some patients with Ebola become disoriented, struggle and thrash, and fall out of bed. They can get a bloody nose, which makes them sneeze. They can have projectile vomiting, and they can cough while they are vomiting. Some become incontinent, and all the fluids that come out of their bodies are increasingly saturated with Ebola particles. The new plastic-walled Ebola ward at Kenema had a type of bed in it, common in African hospitals, known as a cholera bed. A patient with cholera suffers from uncontrollable watery diarrhea. A cholera bed has a plastic-covered mattress with a hole in the center. A bucket is placed on the floor under the hole and the patient defecates through it into the bucket. In the Ebola ward, the nurses were emptying the buckets and trying to keep things clean, but it was impossible. Then some of the nurses began skipping work. In the tropical heat, the smell of the Ebola wards became intense.

Around July 12th, Joseph Fair, who had been working with the World Health Organization in Freetown, two hundred miles away, travelled to Kenema, a drive of several hours, and went looking for his friend Dr. Khan. Fair found him but couldn’t speak with him, he told me later. Khan was inside the plastic Ebola ward, and the place was a mess. There were thirty or more Ebola patients in the ward, lying on cholera beds, and the floor was splashed with everything that can come out of the human body. Khan was making rounds, with one nurse, both of them wearing P.P.E.

Daniel Bausch, an American Ebola doctor who had been helping at Kenema, and his colleagues recently wrote that Khan had remarked, “I am afraid for my life, I must say. . . . Health workers are prone to the disease, because we are the first port of call for somebody who is sickened.” They also quoted Khan’s sister Isatta as saying, “I told him not to go in there, but he said, ‘If I refuse to treat them, who would treat me?’ ” Perhaps Khan was thinking of his predecessor Dr. Conteh, dying in his own ward.

Alex Moigboi, a popular man who had worked in the hospital for many years, came down with Ebola. Then the head nurse, Mbalu Fonnie, a widow who sometimes used the last name Sankoh, and who had worked at the hospital since it opened, in the nineteen-nineties, began feeling weak and shivery and ran a fever. At first, she downplayed her symptoms and continued working seven days a week, fourteen to sixteen hours a day. She hoped that she had malaria, and gave herself an I.V. drip of malaria medicine, but she didn’t get better. She tested positive for Ebola. That same day, two other Kenema nurses, Fatima Kamara and Veronica Tucker, also tested positive for Ebola. Moigboi died on July 19th, and Fonnie died two days later.

Many of the staff at Kenema became terrified and began staying home from work. Khan ended up working in the Ebola wards with little or no support. Sierra Leone’s medical-care system, sparse and rudimentary to begin with, was collapsing under the strain of Ebola, and the international aid groups that worked in Ebola outbreaks were stretched thin. Doctors Without Borders was coping with Ebola patients in a treatment center at Kailahun, in eastern Sierra Leone, fifty miles from Kenema. In Liberia, doctors and nurses with Samaritan’s Purse, a Christian organization, were overrun with patients at a hospital called elwa, near Monrovia. Khan talked regularly with Pardis Sabeti. “We are all alone here,” he said to her one day. She told him that she and her colleagues in the War Room were rushing people and equipment to him, and they were calling around the world, looking for more doctors and more help. “People and help were coming,” Sabeti told me later, “but it was nowhere near enough.”

Sabeti warned Khan about stress and overwork. “The most important thing is your safety. Please take care of yourself.”

He told her, “I have to do everything I can to help these people,” and then he would put on his gear and go back into the Ebola wards. Khan was a general in a battle where many of his troops were dead or fleeing.

On July 19th, at a large staff meeting, people noticed that Khan didn’t look well. The next day, he didn’t come to work. He had isolated himself at home. The following morning, he requested a test. One of the lab technicians went to his house to draw blood: it was positive for Ebola. Khan didn’t want to be treated at Kenema, because he didn’t want his staff to see him develop symptoms, and he felt that his presence would further demoralize them. The next day, he climbed into an ambulance, which carried him along rutted dirt roads to the Ebola ward in Kailahun.

At the treatment center in Kailahun, there was a freezer powered by a generator, and inside the freezer were three small plastic bottles containing a frozen water solution. In it were antibodies, Y-shaped molecules that are produced naturally by the immune systems of mammals as a defense against invading microbes. The liquid was ZMapp, an experimental drug for the treatment of Ebola, and the three bottles amounted to what might be a course of ZMapp for one human being. The drug was untested in humans. During the previous decade, a group of scientists, working with very little money and virtually no encouragement from the community of Ebola experts, had developed the drug. The effort involved dozens of people, but the principal researchers were Larry Zeitlin, the president of Mapp Biopharmaceutical, a biotech company in San Diego; Gene Garrard Olinger, a contractor with the National Institute of Allergy and Infectious Diseases division of the National Institutes of Health; and Xiangguo Qiu and Gary Kobinger, researchers at the Public Health Agency of Canada’s research facility in Winnipeg. ZMapp was a cocktail of three antibodies that seemed especially potent in killing Ebola. Mapp Biopharmaceutical and the manufacturer, Kentucky BioProcessing, had developed a method of growing it in tobacco plants.

In April of 2014, three months before Khan fell ill, Kobinger and his group in Canada tested ZMapp for the first time in monkeys infected with Ebola. They gave the monkeys a thousand times the lethal dose of Ebola. To the researchers’ surprise, the drug saved the monkeys. ZMapp could work even when the animal seemed close to death. Kobinger and his team found that they had to give the animal three doses of ZMapp spaced a few days apart. Kobinger compared this to three punches from a prizefighter: the first two punches knocked Ebola down and the third ended the fight. In late June, while Ebola was starting to blow up across West Africa, Kobinger travelled from his lab in Winnipeg to Kailahun with lab equipment for the doctors there, along with the three plastic bottles of ZMapp, and left the bottles in the Kailahun freezer. He wanted to see how ZMapp held up in the tropical climate, where the heat and an uncertain electricity supply can ruin a drug’s effectiveness. He had no idea that it would be used.

The government of Sierra Leone regarded Humarr Khan’s plight as a national crisis. As soon as Khan became ill, a government official sent out an e-mail to Ebola experts around the world, asking for information about any drug or vaccine that might help him. In a series of international conference calls, officials from the World Health Organization, the U.S. Centers for Disease Control and Prevention, the government of Sierra Leone, the Public Health Agency of Canada, scientists from the United States Army, and health workers from Doctors Without Borders, which was running the Kailahun Ebola center, debated how to treat Khan. Many of the people on the phone knew him, and this was a matter of life and death.

The debate quickly centered on ZMapp, which seemed to show more promise than other drugs. Why should Khan, and not other patients, get any experimental drug? What if he died? ZMapp had been tested in some monkeys a few months earlier, but what was the significance of that? It was made from mouse-human antibodies that had been grown in tobacco plants. If such substances enter the bloodstream, a person might have a severe allergic reaction. If something went wrong with the drug, there was no intensive-care unit in Kailahun. The population of Sierra Leone would be furious if the West was seen to have killed Khan, an African scientist and a national hero, with an experimental drug. But if he wasn’t given the ZMapp, and he died, people might say that the West had withheld a miracle drug from him. “I was making sure my tone of voice stayed neutral,” Kobinger recalled. The debate and the calls went on for three days.

Meanwhile, at the elwa hospital, two hundred miles to the south, a fifty-nine-year-old American health worker named Nancy Writebol got a fever. She tested positive for malaria and went to bed in her house, on the grounds of the hospital, where she lived with her husband, David Writebol. Soon afterward, Kent Brantly, a thirty-three-year-old American doctor with Samaritan’s Purse at elwa, called the medical director of disaster response for Samaritan’s Purse, Lance Plyler. “Don’t freak out, Lance, but I think I’ve got a fever,” Brantly said. He put himself into isolation in his house on the hospital grounds, and Samaritan’s Purse sent a sample of his blood to the National Reference Laboratory of Liberia. Plyler told me that he didn’t want anybody to know that one of his doctors might have Ebola, so he labelled the tube with a fictitious name, Tamba Snell.

The National Reference Lab of Liberia is a former chimpanzee-research center and sits at the end of a dirt road in the forest near Monrovia’s international airport. It is well staffed and well equipped. An American virologist named Lisa Hensley had been working there with Liberian and American colleagues, testing dozens of clinical samples of liquids from the bodies of people suspected of having Ebola. Hensley works with the National Institute of Allergy and Infectious Diseases, and has been doing research on Ebola in U.S. government biocontainment labs for more than fifteen years. She and her colleagues, wearing pressurized P.P.E. suits, were using devices called PCR machines to find out if Ebola was present in the samples, in order to help doctors in Liberia identify people who were infected. Technicians at the lab tested the blood of Tamba Snell. It came up negative for Ebola, and Hensley e-mailed the result to a doctor at Samaritan’s Purse. The real Tamba Snell, Kent Brantly, got sicker.

On July 25th, the international groups finally came to a decision about Humarr Khan. ZMapp was too risky and would not be given to him. Khan was informed; it is not clear that he was brought in to the decision. That same day, his brother Sahid, in Philadelphia, began frantically calling Kailahun in an effort to speak to him. Sahid had been calling Humarr’s cell phone for days but had got no answer. Sahid got somebody at Kailahun on the phone and demanded to speak with his brother. “It is not possible to speak to Humarr,” he was told. Sahid blew up. “Then I want a picture of him to prove he is still alive!” he shouted. Soon afterward, somebody texted him a photo of his brother. In the image, Humarr is sitting on a plastic chair, slumped, and his eyes are heavy-lidded. He appears to be exhausted and turned inward, though a slight smile flickers on his face. Sahid believes that the smile was for the sake of their mother, an attempt to tell her not to worry.

At the lab in Monrovia, Lisa Hensley and her group received another sample from Tamba Snell. Shortly afterward, Hensley got an e-mail from an official with the C.D.C. saying that the blood came from “one of our own.” Hensley understood this to mean that an outbreak responder might have Ebola. Then another sample came in, with the name Nancy Johnson. Hensley knew that the names were fictitious. The lab wasn’t staffed that day—it was July 26th, Liberian Independence Day, a national holiday. Nevertheless, Hensley and a colleague, Randal Schoepp, put on P.P.E. and went into the lab. They began with the blood of Tamba Snell. The machines worked fast: he had Ebola. Hensley e-mailed Lance Plyler: “I am very sorry to inform you that Tamba Snell is positive.” Later that day, she texted him: Nancy Johnson had Ebola, too.

At elwa, Plyler went to the house where Kent Brantly was isolated, in bed, and was distressed to see how ill he looked. “I hate to tell you that you have Ebola,” he said. After a moment, Brantly said, “I really did not want you to say that.” Plyler immediately decided that he would do all he could. He knew that there were experimental drugs for Ebola. Doctors from Samaritan’s Purse sent an e-mail to a C.D.C. official who was stationed in Monrovia: they wanted to talk to a researcher with direct experience in the development of the drugs. They wanted that person to put Plyler in touch with anyone who might have access to these possible therapies.

That person turned out to be Lisa Hensley, the scientist in Monrovia who had just tested Brantly’s and Writebol’s blood. She sent information to Samaritan’s Purse and offered to visit elwa as soon as possible. She couldn’t get out until the following evening, and the roads weren’t entirely safe after dark. The hospitals in Monrovia were full of Ebola patients, and the medical system was crumbling. In the countryside, medical-outreach teams had been attacked by mobs of frightened people. Hensley called the U.S. Embassy in Monrovia and arranged for an Embassy car and driver to take her to elwa. She arrived at ten o’clock that night; Plyler was waiting in his car. They drove through the compound until they came to a small house, painted white, where a lighted window was opened just a crack. Kent Brantly was sitting in bed behind the window, with his laptop. He was researching his case, and he told Hensley that he knew about antibodies to Ebola.

Hensley had done laboratory research on experimental drugs and vaccines for Ebola. Speaking to Brantly through the window, she summarized nineteen possible options. Almost none of them had been tested in humans. In January, Tekmira Pharmaceuticals had begun testing a drug, TKM-Ebola, in humans, evaluating it for safety. It had shown decent results in monkeys, but the drug had been put on partial hold while the company collected more information for the Food and Drug Administration. There was a drug called T705, which had been tested in Japan, in humans, against influenza virus, and it might have some effect on Ebola. Hensley told Brantly that she had participated in a study of a drug called rNAPc2, an anticoagulant made by a company called Nuvelo; the drug saved one of three monkeys it was tested on. Brantly focussed his attention on ZMapp. It had saved monkeys even when they were deep into the illness, as he was now. But, still, he didn’t know. When Hensley finished, Brantly’s voice came out through the window: “What would you do, Lisa?”

ADVERTISEMENT

She couldn’t tell him what to do. “These are all very personal decisions,” she said. Then she told him that she had been exposed to Ebola, sixteen years earlier. At the age of twenty-six, working in a spacesuit with liquids full of Ebola particles, she had cut her finger with scissors, which had gone through two layers of gloves. The only experimental treatment at that time was a horse serum made by the Russians; this could kill her, and she had decided not to use it unless she was certain that she had contracted Ebola. On the night of the accident, after a meeting to analyze what had happened, she was sent home to her apartment. She called her parents and told them that she might come down with Ebola and that they would have to collect her belongings and take her cat home with them.

Brantly listened, and said that he probably would choose ZMapp for himself, based on the data, even though it had never been tested on humans. Hensley offered to donate blood if he had hemorrhages. Plyler then drove her across the compound to Nancy Writebol’s house. Writebol was asleep close to a window. Her husband and a nurse both put on P.P.E. and woke her, and Hensley spoke with her from outside the house. Meanwhile, Hensley noticed that the window was wide open, and Writebol began coughing. A ceiling fan blew gusts of air out the window and across Hensley and the others. Hensley could smell the air from the bedroom. She took a step back but didn’t say anything. Later that night, in her hotel room, Hensley sent a text to Lance Plyler. “You guys make me a little bit nervous,” she typed, and she advised them to wear breathing masks outside the windows of the two patients.

On July 28th, Gary Kobinger, of the Public Health Agency of Canada, received an e-mail from Lance Plyler asking for ZMapp to be sent to elwa as quickly as possible. Kobinger told him that the nearest course of the drug was sitting in a freezer in Kailahun, in Sierra Leone, across an international border. By now, Humarr Khan was close to death. Hensley had not taken part in the debate over whether to give ZMapp to Khan, but she knew about the decision.

The drug would have to be flown from Kailahun, but there was no airfield there; the nearest was in a town called Foya. A few days earlier, a team from the Sierra Leone Ministry of Health had been attacked in Foya, and a ministry vehicle was burned; residents were fleeing the area. The U.S. Embassy in Monrovia asked Lisa Hensley to pick up the drug and arranged a helicopter for her.

“You don’t whisper anymore.”

The chopper was an old gray Russian Mi-8, flown by two Ukrainian pilots. A colonel in the U.S. Marine Corps accompanied her—to provide peace of mind, he told her. A heavy rain was falling, and Hensley and the colonel sat in the helicopter for hours on the tarmac. During those hours, in Kailahun, Humarr Khan died. Finally, during a break in the weather, the helicopter took off and headed north. Hensley, wearing ear protectors, sat buckled on a bench facing the colonel. She could see almost nothing out the window except moisture whipping across the glass, but now and then she caught a glimpse of a ridge covered in jungle slipping by below. She grew anxious, especially when the colonel remarked, “We’ve been flying in periods of zero visibility.”

In this outbreak, everybody was flying in near-zero visibility. Below the helicopter, lost in the rain, Ebola was maneuvering in secret. No drugs or vaccines were known to work against it in people; Hensley was on her way to get one sample of one experimental compound. Later, she told me, “If you are walking by a lake and somebody is drowning, you can’t not try to save them. People are drowning in Ebola.”

She was a single mother, with a nine-year-old son she’d left back in Maryland, in the care of her parents. “If we don’t help, what message are we sending to our children?” she said to me one day. “Our children are going to inherit these problems, and people are dying. Part of the responsibility of a parent is to teach our children how to be responsible. We have to set the example for our staff, our families, and the patients in Africa.”

Hensley dozed off, and when the chopper touched down in Foya she discovered that a plane from Samaritan’s Purse had already left with the drug. The helicopter flew back to Liberia.

At the elwa hospital, Lance Plyler, with the drug now in his hands, agonized about whether he should give it to Writebol or to Brantly. He found some words in the Book of Esther: “Who knows whether you have come to the kingdom for such a time as this?” Writebol was extremely ill by now, but he found Brantly in surprisingly good condition, working on his laptop in bed. Brantly was more concerned about Writebol. “Give the drug to Nancy—I’ll be getting out of here in a couple of days,” he told Plyler. An evacuation jet had been ordered, and he was evidently thinking of that. Still, Plyler put off the decision. Another night passed.

On the morning of July 31st, Plyler went to see Nancy Writebol, and decided to give her the drug. She seemed close to the end stage of Ebola-virus disease; she had developed a sea of red spots and papules across her torso—signs of hemorrhages under the skin—and she was beginning to bleed internally. She could crash at any time: lose blood pressure, go into shock, and die. One of the bottles was taken out of the freezer, and Plyler had Writebol hold it in her armpit to defrost it.

Around seven o’clock that evening, Plyler went to Brantly’s house to see how he was doing. When he looked in the window, he was stunned. Brantly had abruptly gone into the end-stage decline. His eyes were sunken, his face was a gray mask, and he was breathing in irregular gasps. “A clinician knows the look,” Plyler told me later. “He was dying.” Brantly, a clinician himself, realized that he was on the verge of a breathing arrest. With no ventilators at the hospital, he wouldn’t make it through the night.

Plyler made a decision. “Kent, I’m going to give you the antibodies.” He would split the three doses, giving one bottle to Brantly, the second bottle to Writebol, and the third bottle to whichever of them was not evacuated.

A nurse got the bottle from under Writebol’s arm. Writebol said that she was glad for Brantly to have it. While Plyler watched, a doctor named Linda Mabula suited up and went into Brantly’s house, where she prepared an I.V. drip. The plan was to drip the first dose into him very slowly, so that the antibodies wouldn’t send him into shock. Plyler stayed by the window and prayed with Brantly. After less than an hour, Brantly began to shake violently, a condition called rigors. It occurs in people who are near death from an overwhelming bacterial infection. Plyler had a different feeling about these rigors. “That’s just the antibodies kicking the virus’s butt,” he told Brantly through the window.

Three hours later, Lisa Hensley got a text from Lance Plyler: “Kent is about halfway into the first dose. Honestly he looks distinctly better already. Is that possible?” Hensley texted back to say that monkeys on the brink of death had shown improvement within hours. Two days later, having received one dose of ZMapp out of the required three doses, and a blood transfusion from a fourteen-year-old boy who had recovered from Ebola, Kent Brantly walked onto the evacuation plane. At Emory University Hospital, in Atlanta, he received two more doses of ZMapp, which had been sent from the tobacco facility in Kentucky, and was discharged from the hospital after two weeks, free of the virus.

Nancy Writebol had a different experience. She did not improve noticeably when she got the first dose of ZMapp, and she developed intense itching in her hands, which seemed to be an allergic reaction to the drug. She continued to have internal hemorrhages afterward, and was given a blood transfusion to make up what she was losing. Nevertheless, she survived. She was evacuated to Emory University Hospital two days later and received more ZMapp and another blood transfusion there.

As of this writing, the world’s supply of ZMapp is temporarily exhausted. It was given to five more patients with Ebola, including a Spanish priest, who died shortly after getting the first dose. More of the drug is growing in tobacco plants in a building in Kentucky. The plants have enough of the drug in them to make twenty to eighty treatment courses of ZMapp in the next two months, as long as there are no glitches in the process. The U.S. government and Mapp Biopharmaceutical are scrambling to get more plants growing, to increase production, but the scale-up will not be easy. The drug remains untested, and nobody can say whether it will ever become a weapon in the Ebola wars.

At two o’clock in the afternoon on July 31st, the funeral of Humarr Khan began in Kenema. It was attended by five hundred people, including townspeople, scientists, health workers, and Sierra Leone government ministers. Many wept uncontrollably. The gravediggers encountered rocks, and it took them hours to dig deep. At ten o’clock that night, in the moments when Kent Brantly was shaking with rigors as ZMapp flowed into his body, the gravediggers finished burying the body of Khan at the Kenema hospital.

As Khan lay dying, Pardis Sabeti composed a song for him and the other Kenema workers, called “One Truth.” It had the line “I’m in this fight with you always.” She had hoped that some day she could sing it to him, but by then he was already in isolation. When she received the news of his death, she was “absolutely devastated,” she said. “I can’t even begin to describe the feeling of loss for the world.” Equally devastating were the deaths of the staff members who had stayed to work in the wards at Kenema.

Through the summer, Sabeti and her group continued to read the Ebola genomes. They published them in real time, on the Web site of the National Center for Biotechnology Information, so that scientists anywhere could see the results immediately. Then, in late August, they published a paper in Science detailing their results. They had sequenced the RNA code of the Ebolas that lived in the blood of seventy-eight people in and around Kenema during three weeks in May and June, just as the virus was first starting chains of infection in Sierra Leone. The team had run vast amounts of code through the sequencers, and had come up with around two hundred thousand individual snapshots of the virus, in the blood of the seventy-eight people, and had watched it mutate over time. They could see who had given the virus to whom. They could see exactly how it had mutated each time it grew in one person and jumped to the next. The snapshots, taken together, amounted to a short video of Ebola. You could imagine the virus as a school of fish, with each particle of Ebola a fish. The fish were swimming, and as they swam and multiplied they changed, until the school had many kinds of fish in it and was growing exponentially in size, with some kinds of fish better at swimming than others.

“Never get a tattoo when you’re drunk and hungry.”

Gire and Sabeti’s group also found that the virus had started in one person. It could have been the little boy in Meliandou, but there is no way to tell for sure right now. After that, the swarm mutated steadily, its code shifting as it palpated the human population. As the virus jumped from person to person, about half the time it had a mutation in it, which caused one of the proteins in the virus to be slightly different. By the time the virus reached Sierra Leone, travelling in the bodies of the women who had attended the funeral of the faith healer, it had become two genetically distinct swarms. Both lineages of the virus moved from the funeral into Sierra Leone. Already, some of the mutations were making Ebola less visible to the tests for it.

“It shows that you can analyze Ebola in real time,” Sabeti said. “This virus is not a single entity. Now we have an entry into what the virus is doing, and now we can recognize what we are battling with at every point in time.”

The Science paper included five authors who died of Ebola, including Humarr Khan, the head nurse Mbalu Fonnie, and the nurse Alex Moigboi. “There are lifetimes in that paper,” Sabeti said. A thousand more vials of human blood with Ebola in them are sitting in freezers in Kenema waiting for bureaucratic clearance so that they can be flown to Harvard and sequenced in the machines, and scientists can see what the swarm has been doing more recently.

The question often asked is whether Ebola could evolve to spread through the air in dried particles, entering the body along a pathway into the lungs. Eric Lander, the head of the Broad Institute, thinks that this is the wrong question to ask. Lander is tall, with a square face and a mustache, and he speaks rapidly and with conviction. “That’s like asking the question ‘Can zebras become airborne,’ ” he said. In order to become fully airborne, Ebola virus particles would need to be able to survive in a dehydrated state on tiny dust motes that remain suspended in the air and then be able to penetrate cells in the lining of the lungs. Lander thinks that Ebola is very unlikely to develop these abilities. “That would be like saying that a virus that has evolved to have a certain life style, spreading through direct contact, can evolve all of a sudden to have a totally different life style, spreading in dried form through the air. A better question would be ‘Can zebras learn to run faster?’ ”

There are many ways by which Ebola could become more contagious even without becoming airborne, Lander said. For example, it could become less virulent in humans, causing a milder disease and killing maybe twenty per cent of its victims instead of fifty per cent. This could leave more of them sick rather than dead, and perhaps sick for longer. That might be good for Ebola, since the host would live longer and could start even more chains of infection.

In the lab in Liberia, Lisa Hensley and her colleagues had noticed something eerie in some of the blood samples they were testing. In those samples, Ebola particles were growing to a concentration much greater than had been seen in samples of human blood from previous outbreaks. Some blood samples seemed to be supercharged with Ebola. This, too, would benefit the virus, by enhancing its odds of reaching the next victim.

“Is it getting better at replicating as it goes from person to person?” Hensley said. She isn’t at all sure; maybe in previous outbreaks some people had had these profusions of particles in their blood. “We have to go back to the lab to answer this question.”

Sun Tzu, the great Chinese strategist, wrote that one of the rules of war is to know the enemy. Sabeti and her team now had a way to watch Ebola as it changed; they had the enemy in sight. This meant that the tests for Ebola could be updated quickly as the virus changed, and that the scientists might also be able to see it mutating in some dangerous direction.

Meanwhile, scientists have been developing weapons against the virus and are starting to test them. The scientists who came up with ZMapp, along with Kentucky BioProcessing, were racing to increase the production of ZMapp and to get it tested as a new drug in patients infected with Ebola. The hope is to get the drug through clinical trials and gain the support of a regulatory agency. Even at increased production speed, the supply of ZMapp would still be nowhere near enough to treat the population, but it might be enough—provided it was effective—to kill Ebola in some infected people. If there were a drug that could save somebody from Ebola, this might help encourage health professionals to work in Ebola wards, knowing that there would be a treatment for them if they got infected.

In addition to many drug candidates, there are vaccines in development. In early September, the National Institutes of Health began testing a vaccine, made by a division of GlaxoSmithKline and based on an adenovirus, on twenty volunteers. Another vaccine, called vsv-ebov, developed by the Public Health Agency of Canada and licensed to NewLink Genetics, started human trials last week. It seems possible that some time next year a vaccine may be available for use on people who have already been exposed to Ebola, though it will still not be cleared for general use. If a vaccine is safe and shows effectiveness against Ebola, and if it can be transported in the tropical climate without breaking down, then vaccinations against Ebola could someday begin.

If a vaccine works, then the vaccinators might conceivably set up what’s known as ring vaccinations around Ebola hot spots. In this technique, medical workers simply vaccinate everybody in a ring, miles deep, around a focus of a virus. It works like a fire break; it keeps the fire from spreading. Ring vaccination was the key to wiping out the smallpox virus, which was declared eradicated in 1979, but whether the ring technique—provided there was a good vaccine—would work against Ebola nobody can say. In any case, epidemiologists would not give up trying to trace cases in order to break the chains of infection.

In the U.S. and Europe, hospitals have made fatal mistakes in protocol as they engage with Ebola for the first time—errors that no well-trained health worker in Africa would likely make. But they will learn. By now, the warriors against Ebola understand that they face a long struggle against a formidable enemy. Many of their weapons will fail, but some will begin to work. The human species carries certain advantages in this fight and has things going for it that Ebola does not. These include self-awareness, the ability to work in teams, and the willingness to sacrifice, traits that have served us well during our expansion into our environment. If Ebola can change, we can change, too, and maybe faster than Ebola. ♦

Published in the print edition of the October 27, 2014, issue.

2014 (Nov 04) - USA Army website : "USAMRIID supports Ebola Virus Disease outbreak response in West Africa"

By Caree Vanderlinden, Army MedicineNovember 4, 2014 / PDF of article : [HG00GC][GDrive]

Also mentioned : Western African Ebola virus epidemic (2013 - 2016) / Sina A Bavari (born 1959) /

FORT DETRICK, Md. (Oct. 22, 2014) -- From on-site laboratory support in Liberia, to training of key personnel, to accelerated research efforts on diagnostic, vaccine and treatment approaches, the U.S. Army Medical Research Institute of Infectious Diseases is playing a significant role in assisting the Ebola Virus Disease outbreak response in West Africa.

Ebola virus causes a severe, often fatal hemorrhagic disease in humans and non-human primates. Currently there are no licensed vaccines or drugs to fight the disease, and case fatality rates as high as 90 percent have been reported in past outbreaks. As of Oct. 15, the World Health Organization reported at least 8,997 cases and 4,493 deaths in seven affected countries. These include Guinea, Liberia, Nigeria, Senegal, Sierra Leone and Spain, as well as the first-ever case of Ebola diagnosed in the U.S.

That patient, a man who had recently traveled from Liberia to the U.S., died Oct. 8.

The U.S. Department of Defense is supporting the U.S. Agency for International Development as part of a U.S. whole of government response effort to the Ebola virus outbreak, as announced by President Barack Obama on Sept. 16. U.S. military personnel are deploying to West Africa in support of the effort, called Operation United Assistance. In addition to setting up a regional staging base to facilitate transportation of equipment, supplies and personnel, the U.S. military is establishing additional treatment centers in Liberia and providing medical personnel to train health-care workers in the region.

At the U.S. Army Medical Research Institute of Infectious Diseases, known as USAMRIID, the response effort spans the institute's research and support divisions and there is no sign of the operational tempo slowing any time soon, according to Col. Erin P. Edgar, commander of the institute.

"This is definitely not business as usual," he said.

Late September, USAMRIID was asked to provide training to deploying U.S. forces, according to Lt. Col. Neal E. Woollen, who directs the institute's biosecurity program. Several personnel have volunteered to serve on mobile training teams that travel to deploying units to train and certify troops who will be working in Ebola-affected areas of West Africa. Training is focused on proper wearing of protective equipment, as well as decontamination procedures.

ON-SITE LABORATORY SUPPORT

Since April 2014, USAMRIID and the National Institute of Allergy and Infectious Diseases-Integrated Research Facility have provided personnel, training and diagnostic laboratory support to the Liberian Institute for Biomedical Research on a continuous rotational basis, according to Randal J. Schoepp, Ph.D., chief of USAMRIID's Applied Diagnostics branch. He and several others helped to set up an Ebola virus testing laboratory in Liberia and trained local personnel to run diagnostic tests on suspected Ebola hemorrhagic fever clinical samples.

Schoepp said USAMRIID has been working on a collaborative project in West Africa since 2006 (see sidebar article below). Because the team was working on disease identification and diagnostics in the region, he added, "We had people on hand who were already evaluating samples and volunteered to start testing right away when the current Ebola outbreak started."

In addition to providing laboratory testing and training support for the current outbreak, USAMRIID has provided more than 10,000 Ebola laboratory tests, referred to in the medical community as assays, to support laboratory capabilities in Liberia and Sierra Leone. The institute also supplied personal protective equipment to Metabiota Inc., a non-government organization involved in the testing.

Edgar called the project "a great example of medical diplomacy at work."

"This collaboration allows USAMRIID to bring our expertise to bear in responding to an international health crisis," he said. "In addition, it enables us to test the medical diagnostics that we develop in a real-world setting where these diseases naturally occur."

DIAGNOSTIC TOOLS

USAMRIID research led to the only assay currently authorized to diagnose Ebola in U.S. citizens, according to David A. Norwood, Ph.D., chief of USAMRIID's Diagnostic Systems Division. The assay, which detects the Zaire strain of Ebola virus in patient samples, is called the Ebola Zaire Real-Time PCR Assay Test Kit. It was developed, manufactured and tested with help from the U.S. Army Medical Materiel Development Activity.

While the test has not been approved by the U.S. Food and Drug Administration, the FDA has authorized its use under an Emergency Use Authorization, granted in August 2014. According to Norwood, the EUA provides a legal basis for the use of unapproved medical products, including diagnostics, in a declared emergency when there are no alternatives. The test is available at authorized DOD laboratories in the U.S. and overseas, as well as select CDC Laboratory Response Network state public health labs throughout the country for testing U.S citizens.

"This assay is also being used in West Africa for rapid diagnosis of host nation patients," said Norwood. "So there is no disparity between the diagnostic capabilities that are being used in-country and those that are available for testing U.S. citizens. While the labeling and execution is somewhat different for regulatory purposes for testing U.S. citizens, the same capability is available for diagnostic testing for everyone."

Issuance of the EUA was a collaborative effort among several agencies: Medical Countermeasure Systems, U.S. Army Medical Command; Health Affairs, Readiness Division, Health Care Operations Directorate; Joint Program Executive Office Critical Reagents Program; the DOD Clinical Laboratory Improvement Program Office; and the recipient laboratories, including five DOD labs and 15 CDC-LRN state public health laboratories.

DRUG AND VACCINE RESEARCH

USAMRIID is leading the evaluation of several promising Ebola medical countermeasure candidates, including therapeutics and vaccines, according to scientific director [Sina A Bavari (born 1959)], Ph.D.

Bavari, an expert at building public-private partnerships, says the current outbreak offers researchers an opportunity to accelerate the development of medical products to prevent and treat the disease through collaboration with pharmaceutical companies and other government agencies.

Among the products being evaluated by USAMRIID are four potential therapies, including synthetically made, small-molecule drugs that have shown efficacy against a broad range of viral diseases, according to Bavari. One of these drugs, known as BCX4430, has been tested in animal models at USAMRIID; its parent company is in the process of filing an Investigational New Drug application with the FDA to begin Phase I clinical trials in humans.

Two other compounds of interest are oral favipiravir, dubbed T-705, which is already in Phase III clinical trials as a potential influenza treatment, and AL-8176, currently is in Phase II clinical trials for Respiratory Syncytial Virus.

"If we can evaluate a drug that's already in development for another use, and show that it has potential against Ebola virus, that saves us years of research and development," [Sina A Bavari (born 1959)] explained.

The fourth therapeutic candidate being studied at USAMRIID is Z-Mapp, a "cocktail" of three antibodies, one of which was developed by USAMRIID. This drug made headlines when it was used to treat a handful of people infected during the current outbreak, including two American aid workers who contracted Ebola in Liberia and recovered at Emory University Hospital in Atlanta, Georgia.

Previous studies at USAMRIID with an earlier version of Z-Mapp showed that it could protect monkeys from Ebola even when administered five days after infection, according to John M. Dye, Ph.D., branch chief for viral immunology. He said additional studies of Z-Mapp in nonhuman primates will begin at USAMRIID later this month. Those efforts will help to determine dosing -- the optimal amounts of antibody that can be safely administered and still provide protection.

In addition, there are a number of Ebola virus vaccine platforms in various stages of development, Dye said. Two that have been studied extensively at USAMRIID are the VLP (virus-like particle) and the VRP (virus replicon particle) vaccine approaches. Other vaccine approaches include those based on adenovirus (currently in Phase I clinical trials) as well as the rVSV (recombinant vesicular stomatitis virus) platform.

USAMRIID's Division of Medicine is providing medical monitor support to the Phase I clinical trial of the rVSV vaccine, scheduled to begin this month at the Walter Reed Army Institute of Research.

According to [Sina A Bavari (born 1959)], USAMRIID is continuing to investigate potential treatments and vaccine candidates for Ebola, with several laboratory and nonhuman primate studies scheduled for the near future. The success of these research efforts will depend, in part, on future funding levels.

REWARDING EXPERIENCE

It's not often that USAMRIID scientists get to take their expertise out of the laboratory and into a field setting. For Schoepp, the experience has been "rewarding," though he says he'll be ready to stay home for a while after completing his fourth trip to West Africa in just six months.

"What makes me really proud is that the laboratory staff we trained [in West Africa] jumped right into the fray, and thanks to the training we provided, they didn't even blink," said Schoepp. "They started testing right away; they knew what to do."

While the scientists at the Liberian Institute for Biomedical Research put in long, hot hours wearing protective gear in the laboratory, their work environment is far from the only challenge they face, according to Schoepp. Diagnostics personnel are under a great deal of pressure to run the tests accurately, because the results they provide to the health care team literally can mean the difference between life and death for a patient.

"It's critical to diagnose Ebola-infected individuals, of course, but it's also important to tell people they're not infected," he said. "Being able to give them an answer -- so they can go home and not worry -- that's pretty satisfying."

[...]

SIDEBAR NEWS ARTICLE:

Sierra Leone Samples: Evidence of Ebola in West Africa in 2006

A study published in July 2014, in the journal, Emerging Infectious Diseases, showed that Ebola virus has been circulating in the region since at least 2006 -- well before the current outbreak.

According to first author Randal J. Schoepp, Ph.D., of USAMRIID, between 500 and 700 samples are submitted each year to the Kenema Government Hospital Lassa Diagnostic Laboratory in Sierra Leone. Generally, only 30 to 40 percent of the samples test positive for Lassa fever, so the aim of this study was to determine which other viruses had been causing serious illnesses in the region.

Using assays developed at USAMRIID that detect the presence of IgM, an early protein produced by the body to ward off infection, the research team found evidence of dengue fever, West Nile, yellow fever, Rift Valley fever, chikungunya, Ebola and Marburg viruses in the samples collected between 2006 and 2008. About two-thirds of the patients had been exposed to these diseases, and nearly 9 percent tested positive for Ebola virus.

In addition, of the samples that tested positive for Ebola, the vast majority reacted to the Zaire strain, which was unexpected, according to the authors.

"Prior to the current outbreak, only one case of Ebola had ever been officially reported in this region, and it was from the Ivory Coast strain," said Schoepp. "We were surprised to see that Zaire -- or a variant of Zaire -- was causing infection in West Africa several years ago."

The laboratory testing site in Kenema has been supported by the Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance and Response System. In collaboration with the host country, the site enables collection of samples that can be used in research toward new medical countermeasures, and allows USAMRIID to evaluate the performance of previously developed laboratory tests using samples collected on site. USAMRIID hopes to eventually obtain viral isolates for medical countermeasure development and receive data on the performance of the diagnostic assays.

Other contributors to the work include the Department of Defense Joint Program Executive Office-Critical Reagents Program, the Defense Threat Reduction Agency Cooperative Biological Engagement Program and the DTRA Joint Science and Technology Office.

Related Links:

CSPAN VIDEO

DECEMBER 16, 2014

Ebola Vaccine Research

Dr. Anthony Fauci and others talked about efforts to develop a vaccine against the Ebola virus. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, and Julie Gerberding, former Centers for Disease Control and Prevention (CDC) director under President George W. Bush, were among the panelists. close


https://mobile.twitter.com/ncovafrica/status/1230153328459423744

CoViD19-ΛFЯICΛ

@NCoVAfrica

Liberia The National reference lab of Liberia (NRL) in #Morovia has the capacity to test for #covid19. @WHOAFRO has particpated for the supply of reagents. #AfricaPrepares #nCoVAfrica

10:33 AM · Feb 19, 2020·Twitter Web App

2020-02-19-twitter-ncovafrica-1230153328459423744.jpg

https://pbs.twimg.com/media/ERJhVpFWsAM0o7U?format=jpg&name=medium

2020-02-19-twitter-ncovafrica-1230153328459423744-ERJhVpFWsAM0o7U.jpg

The "National Public Health Institute of Liberai" is not the same as "The Naitonal reference laboratory (Monrovia")"

2022-04-04-google-maps-img-1-national-ref-lab-monrovia

2022-04-04-google-maps-img-1-national-public-health-institute-of-liberia