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Rashid A. Chotani, MD, MPH Adjunct Professor, GWU [email protected] Prepare Proactively Seek Focus Openly Innovate Speed Matters Outline History Reservoir How does the disease spread Current Epidemic • West Africa • Europe • US Treatment Modalities State of the Art of Current Vaccines, Therapeutics and Diagnostic Devices Discussion History Ebola virus disease (EVD) (formerly known as Ebola haemorrhagic fever) is a severe disease caused by a virus of the filovirus family, which occurs in humans and non-human primates 1976: It first appeared simultaneously in Nzara, Sudan and Yambuku in the Democratic Republic of Congo (DRC) Two strains were identified; Sudan & Zaire 1989: The third strain, was discovered in Reston, VA It caused severe illness in non-human primates but not in humans. Virus was found in a colony of monkeys imported from the Philippines Subsequently caused outbreaks in non-human primates in Pennsylvania (Philadelphia), Texas (Alice) and Italy (Sienna) Several research workers became infected with the virus during these outbreaks, but did not become ill 1994: The forth strain was discovered during necropsy in Cote D’Ivoire, and outbreaks have been occurring with increasing frequency since. 2008: A fifth strain, from Uganda called the Bundibugyo was identified. In Africa, outbreaks of EVD primarily occur in remote villages close to tropical rainforests in Central and West Africa Confirmed cases of EVD have been reported in the Democratic Republic of the Congo (DRC, formerly Zaire), Sudan, Gabon, Uganda, Republic of Congo, Cote d’Ivoire, and for the first time in Guinea, Liberia and Sierra Leone in 2014. History There are 5 species of Ebola virus Human Disease: Zaïre ebolavirus (EBOV) Sudan ebolavirus (SUDV) Tai Forest (TAFV) (formerly known as Ebola Ivory Coast) Bundibugyo ebolavirus (BDBV) Non-Human Primate Disease Reston ebolavirus (RESTV) Year Country Ebola virus species Cases Deaths Case fatality rate 1976 1976 Zaire (DRC) Zaire 318 280 88% Sudan Sudan 284 151 53% 1976 England Sudan 1 0 0% 1977 Zaire (DRC) Zaire 1 1 100% 1979 Sudan Sudan 34 22 65% 1989 USA Reston 0(a) 0 0% 1990 USA Reston 0(a) 0 0% 1992 Italy Reston 0(a) 0 0% 1994 Gabon Zaire 52 31 60% 1994 Côte d’Ivoire Tai Forest 1 0 0% 1995 Zaire (DRC) Zaire 315 254 79% 1996 Gabon Zaire 31 21 57% 1996 Gabon Zaire 60 45 75% 1996 South Africa Zaire 1 1 100% 2000-1 Uganda Sudan 425 224 53% 2001-2 Gabon and Zaire (DRC) Zaire 124 97 78% 2002-3 Zaire (DRC) Zaire 143 128 89% 2003 Zaire (DRC) Zaire 35 29 83% 2004 Sudan Sudan 17 7 41% 2005 Zaire (DRC) Zaire 12 10 75% 2007 Zaire (DRC) Zaire 264 187 71% 2007 Uganda Bundibugyo 149 37 25% 2008 Philippines Reston 0(b) 0 0% 2008-9 Zaire (DRC) Zaire 32 14 47% 2011 Uganda Sudan 1 1 100% 2012a Uganda Sudan 24 17 70% 2012b Uganda Sudan 7 4 40% 2012 Zaire (DRC) Bundibugyo 57 29 55% 2388 1590 67% Total Ebola & Marburg Outbreaks in Africa 1976 to 2014 Reservoir • • • • New evidence strongly implicates fruit-bats as the reservoir host for ebolavirus, thought the means of local enzootic maintained and transmission within bat population remains unknown Epizootics caused by ebolavirus appear sporadically, causing high mortality among non-human primates and duikers and may precede human outbreaks Little is known about how the virus first passes to humans, triggering waves of human-to-human transmission, and epidemics With the current evolving epidemic there is an urgent need to better understand the ecology of Ebola virus in nature. How Does the Disease Spread? Geographic Distribution of EVD and Fruit Bats of Pteropodidae Family Geographic Distribution of EVD Outbreaks in Humans & Animals Human to Human Transmission • • • • The way in which the virus first appears in a human at the start of an outbreak is unknown The first patient becomes infected through contact with an infected animal, such as a fruit bat or primate (apes and monkeys), which is called a spillover event Person-to-person transmission follows and can lead to large numbers of affected people In some past Ebola outbreaks, primates were also affected by Ebola, and multiple spillover events occurred when people touched or ate infected primates. Human to Human Transmission • Once infection occurs in humans, the virus can be spread in several ways to others: • Through direct contact • • Through blood or body fluids of a person who is sick with Ebola • • Including but not limited to urine, saliva, sweat, feces, vomit, breast milk, and semen Objects • • Broken skin or mucous membranes in, for example, the eyes, nose, or mouth Like needles and syringes that have been contaminated with the virus From infected fruit bats or primates • Apes and monkeys Human to Human Transmission • • • • • Ebola is not spread through the air or by water, or in general, by food In Africa, Ebola may be spread as a result of handling bushmeat (wild animals hunted for food) and contact with infected bats There is no evidence that mosquitos or other insects can transmit Ebola virus Only a few species of mammals (for example, humans, bats, monkeys, and apes) have shown the ability to become infected with and spread Ebola virus Once someone recovers from Ebola, they can no longer spread the virus. However, Ebola virus has been found in semen for up to 3 months • Abstinence from sex (including oral sex) is recommended for at least 3 months. If abstinence is not possible, condoms may help prevent the spread of disease. Ebola Cases Globally: 17-July to 17October 2014 (weekly) The number of cases in Nigeria, Senegal, USA, Spain, DRC (separate strain) are small and shown on the next slide Ebola Cases Globally: 17-July to 17October 2014 (weekly) The number of cases in Nigeria, Senegal, USA, Spain, DRC (separate strain) are small and shown on the next slide Confirmed & Probable Cases of Ebola 29 August 2014, WHO Confirmed & Probable Cases of Ebola 16 September 2014, WHO Confirmed & Probable Cases of Ebola 03 October 2014, WHO Confirmed & Probable Cases of Ebola 20 October 2014, WHO Status as of 29 October 2014 (WHO) Status as of 24 November 2014 (WHO) • • • • • • • • • • • Total # of EVD Cases: 14,414 Total # of Deaths: 5,178 Case-Fatality Rate: ~36% Senegal declared outbreak free: 17 October Nigeria declared outbreak free: 19 October Spain declared outbreak free: 2 December The outbreak remains intense in Guinea, Liberia & Sierra Leone All districts in Liberia & Sierra Leone have now reported one case of EDV High risk to Ivory Coast due to proximity of cases in Guinea = Ebola Free Status as of EVD in HCW 17 November 2014 (WHO) • • • • Total # of EVD Cases: 588 Total # of Deaths: 337 Case-Fatality Rate: ~57% Early indication: Cause of infection occurred outside the context of EVD Treatment and care WHO declares end of Ebola outbreak in Nigeria • Ebola virus was introduced into Nigeria on 20 July 2014 when an infected Liberian man arrived by airplane into Lagos, Africa's most populous city • • According to WHO recommendations, the end of an Ebola virus disease outbreak in a country can be declared once 42 days have passed and no new cases have been detected • • The man, who died in hospital 5 days later, set off a chain of transmission that infected a total of 19 people, of whom 7 died The 42 days represents twice the maximum incubation period for Ebola (21 days). This 42-day period starts from the last day that any person in the country had contact with a confirmed or probable Ebola case 19 October, Nigeria reached that 42-day mark and is now considered free of Ebola transmission. Europe • October 6, a 44 year old Spanish nurse assistant became the first person known to have contracted Ebola in Europe • The nurse had treated two Spanish missionaries who died of the disease after being flown home from the region • Three other people, including the nurse's husband, have been quarantined • October 20, was clear of all traces of the virus. USA: Chronology of Events • September 30, 2014, the first laboratory-confirmed case of Ebola to be diagnosed in the United States in Thomas Eric Duncan (Index Case) who had traveled to Dallas, Texas from Liberia • • • • • • • He did not have symptoms when leaving Liberia, but developed symptoms approximately four days after arriving in the United States He was missed diagnosed at Texas Presbyterian Hospital of Dallas and sent home On his second visit, after developing symptoms consistent with Ebola and based on his travel history, CDC recommended testing for Ebola The medical facility isolated the patient (i.e., index patient) and sent specimens for testing at CDC and at a Texas laboratory Local public health officials identified all close contacts of the index patient for daily monitoring for 21 days after exposure The index patient passed away on October 8 Doctor & HCW brought to Emory for treatment • October 8, Duncan USA: Chronology of Events • October 10, a HCW (Nina Pham) at Texas Presbyterian Hospital who provided care for the index case tested positive for Ebola. • • She was isolated and subsequently moved to the National Institutes for Health (NIH) Clinical Center October 24, she recovered and discharged • October 15, second HCW (Amber Vinson) who provided care for the index patient at Texas Presbyterian Hospital tested positive for Ebola • • • • She was transferred to Emory University Hospital in Atlanta, Georgia She had traveled by air October 13, the day before reporting symptoms All passengers and crew on the two flights (Dallas to Cleveland on October 10, and Cleveland to Dallas on October 13) have since been contacted by public health professionals and are being monitored Doctors can no longer detect the virus in her body. USA: Chronology of Events • October 23, the New York City Department of Health and Mental Hygiene reported a case of Ebola in a medical aid worker (Craig Spencer) who had returned to New York City October 17 from Guinea, where the medical aid worker had served with Doctors Without Borders. • • • October 26, the New York City Department of Health and Mental Hygiene reported a possible case of Ebola in a 5 year old child who had temperature and he and his family had visited Guinea for a month he had arrived at JFK Airport on October 25 • • Diagnosis was confirmed by CDC on October 24 He is in isolation in a New York City hospital, and public health officials are investigating and conducting contact tracing October 27, Patent tested negative October 27, the Maryland Department of Health & Mental Hygiene reported a suspected case of Ebola admitted to University of Maryland Medical Center • October 28, Patent tested negative USA: Chronology of Events • October 27, CDC outlines plan to monitor travelers • • Most healthcare workers returning from West Africa's Ebola hot zone would be considered to be at "some risk" for infection, while healthcare workers tending to Ebola patients at U.S. facilities would be seen as "low but non-zero" risk Guidelines short of controversial mandatory quarantines being imposed by some U.S. states • October 27, US DOD comes up with its own policy • • • Well beyond previously established military protocols U.S. Army isolates about a dozen soldiers at part of a U.S. base in Vicenza, Italy, including Major General Darryl Williams, who oversaw the initial response to the Ebola outbreak Dozens more will be isolated in the coming days as they rotate out of West Africa, where the military has been building infrastructure to help health authorities treat Ebola victims. USA: Ebola Contact Tracing, Dallas, Texas Date: 10/27/2014 Confirmed Cases: 4 Contacts* Current: 1 Completed Surveillance†: 10 Total: 11 Possible Contacts** Current: 96 Completed Surveillance†: 69 Total: 165 Totals Current: 97 Completed Surveillance†: 79§ Total: 176 Contacts are defined as people who had recognized exposure to an Ebola patient, blood, bodily fluids, specimens of an Ebola patient or potentially contaminated surfaces. Possible contacts are defined as people who had possible exposure to an Ebola patient, blood, body fluids, specimens of an Ebola patient or potentially contaminated surfaces. *Contacts: Definite exposure **Possible Contacts: Possible exposure †Completed active surveillance §Data for last date of exposure is still in progress 6 November, The World Health Organization reports that, of the 177 possible contacts identified, only 53 remain under monitoring. The other 124 have completed their 21-day monitoring period without symptoms USA: Chronology of Events • November 8, All contacts of the three Ebola cases in Texas have completed 21 days of monitoring. None had Ebola • November 11, The doctor who was treated at Bellevue Hospital Center in New York is free of Ebola. He has been discharged from the hospital • November 13, The latest World Health Organization Ebola Response Roadmap has confirmed that all the three healthcare workers have been treated and discharged. Overall, there have been four cases and one death. Currently, no contacts are being monitored in the country • November 15, a surgeon from Sierra Leone infected with Ebola was evacuated to the Nebraska Medical Center • November 17, The Nebraska Medical Center has announced that the doctor evacuated from Sierra Leone has died. He was in a critical condition when he arrived on 15 November and despite being treated with convalescent plasma and ZMapp, he passed away as a result of his Ebola disease India: Possible Case • November 18, CDC outlines plan to monitor travelers • • • • a 26-year-old man who recovered from Ebola and returned from Liberia was admitted to the Raiganj District Hospital in West Bengal for testing. He arrived in Dehli on November 10. Three blood samples from the man tested negative for the disease, which means he is considered recovered according to standards set by the WHO and the CDC The CDC advises Ebola survivors to avoid sex for three months or use condoms because the virus can continue to be found in semen for seven weeks after recovery from the disease. Sexual transmission of Ebola has not been definitively established, though multiple studies have shown that the virus can persist in semen for longer than in blood or other body fluids Delhi airport quarantined six people at high-risk suspected with Ebola on November 17. Health officials at airport are monitoring the situation very closely. As of October 21, 18 cases were being treated outside of West Africa • Symptoms may appear anywhere from 2 to 21 days after exposure to Ebola, but the average is 8 to 10 days. • Recovery from Ebola depends on good supportive clinical care and the patient’s immune response. • People who recover from Ebola infection develop antibodies that last for at least 10 years. CDC: Management of Possible Ebola Cases in a Hospital Setting 1. Identify Exposure History: Has patient lived in or travelled to a country with widespread Ebola transmission or had contact with an individual with confirmed EVD within the previous 21 days Y E S 2. Identify Signs & Symptoms: Fever: >100.4 F or 38.0 C or Ebola compatible Symptoms: Headache, weakness, muscle pain, vomiting, diarrhea, abdominal pain or hemorrhage Y Y E E S S 3. Isolate and determine personal protective equipment (PPE) needed: Place patent in private room or separate enclosed area with private bathroom or covered, bedside commode. Only essential personnel with designated roles should evaluate patent and provide care to minimize transmission risk. The use of PPE should be determined based on patient critical status Y E S NO NO Continue with usual triage & assessment A. B. C. Continue with usual triage & assessment B. Notify relevant Health Department Monitor fever and symptoms for 21 days after last exposure in consultation with relevant Health Department 4. Inform: IMMEDIATELY inform the hospital infection control program and other appropriate staff IMMEDIATELY report to the Health Department Use PPE designated for the care of hospitalized patients http://www.cdc.gov/vhf/ebola/hcp/procedures-forppe.html If the patient requires active resuscitation, this should be done in a pre-designated area using predesignated equipment. For clinically stable patients, healthcare worker should at a minimum wear: A. Face shield & surgical face mask B. Impermeable gown C. 2 pairs of gloves If patient’s condition changes, reevaluate PPE 5. Further evaluation and management A. Complete history and physical examination; decision to test for Ebola should be made in consultation with relevant health department B. Perform routine interventions (e.g. placement of peripheral IV, phlebotomy for diagnosis) as indicated by clinical status C. Evaluate patient with dedicated equipment (e.g. stethoscope) EDPLN Laboratories for Ebola or Marburg Diagnostics Diagnosing Diagnosing Ebola in an person who has been infected for only a few days is difficult, because the early symptoms, such as fever, are nonspecific to Ebola infection and are seen often in patients with more commonly occurring diseases, such as malaria and typhoid fever However, if a person has the • Early symptoms of Ebola and has had • • • Contact with the blood or body fluids of a person sick with Ebola Contact with objects that have been contaminated with the blood or body fluids of a person sick with Ebola, or Contact with infected animals, They should be isolated and public health professionals notified. Samples from the patient must be collected and tested to confirm infection. Laboratory Findings at Admission • • • • • • Leukopenia frequently with lymphopenia followed later by elevated neutrophils and a left shift Platelet counts are often decreased in the 50,000 to 100,000 range Amylase may be elevated, reflecting pancreatic involvement (inflammation/infection) Hepatic transaminases are elevated with aspartate aminotransferase (AST) exceeding alanine aminotransferase (ALT); these values may peak at more than 1,000 IU/L. Proteinuria may be present Prothrombin (PT) and partial thromboplastin times (PTT) are prolonged and fibrin degradation products are elevated, consistent with disseminated intravascular coagulation (DIC). Diagnostics Test Timeline of Infection Diagnostic tests available • • • • Antigen-capture enzyme-linked immunosorbent assay (ELISA) testing IgM ELISA Polymerase chain reaction (PCR) Virus isolation Later in disease course or after recovery • IgM and IgG antibodies Retrospectively in deceased patients • • • Immunohistochemistry testing PCR Virus isolation Within a few days after symptoms begin Diagnostics • • August 5, FDA issued an emergency-use authorization for the Defense Department’s real-time polymerase chain reaction assay for Ebola October 25, FDA issues emergency authorization for two new Ebola tests • • BioFire's tests can detect Ebola in a blood or urine sample in one hour, compared with the 24 to 48 hours current tests take to deliver results The test can also be performed in a hospital with BioFire lab equipment, whereas current tests need to be sent to specialized labs. Diagnostics • The new tool, developed by France's Atomic Energy Commission, could allow doctors to diagnose a patient with suspected Ebola in under 15 minutes • • French pharmaceutical company Vedalab is turning the process into a user-friendly kit called Ebola eZYSCREEN. Similar to a DIY pregnancy test, a positive result sees a small stripe showing up in a results window on the hand-held device The kit is simple to use in the field without any additional equipment, said the CEA, which also does non-nuclear research with a possible military or security application. Treatment Modalities • There are no approved treatments available for EVD • Clinical management should focus on supportive care of complications, such as hypovolemia, electrolyte abnormalities, hematologic abnormalities, refractory shock, hypoxia, hemorrhage, septic shock, multiorgan failure, and DIC • Recommended care includes volume repletion, maintenance of blood pressure (with vasopressors if needed), and maintenance of oxygenation, pain control, nutritional support, as well as treating secondary bacterial infections and pre-existing comorbidities. Treatment Modalities • Among patients medically evacuated from West Africa with EVD, large volumes of intravenous fluids have often been required to correct dehydration due to diarrhea and vomiting • Some patients may develop profound thirdspacing of fluids due to vascular leak. • Some organizations have suggested the addition of broad-spectrum antimicrobials, particularly in patients with evidence of septic shock • Infection prevention and control measures are a critical part of clinical management – all bodily fluids and clinical specimens should be considered potentially infectious. Treatment Modalities: Vaccines • There are no approved vaccines available for EVD. Several investigational Ebola vaccines are in development, and Phase I trials are underway for some vaccine candidates... Treatment Modalities: Vaccines Under Development Vaccine Type How does it work State of Research Safety in Humans Availability Chimpanzee adenovirus serotype 3 (ChAd3) vaccine Uses a chimpanzee adenovirus that does not grow, containing the gene for EVD surface protein A single dose of the vaccine given one month in advance protected 16/16 animals from a lethal dose of EVD Over 1,300 humans have received similar vaccines for other diseases, with over 1,000 in Burkina Faso, Gambia, Kenia, and Senegal. These other vaccines seem so far to be safe. However, there is no safety information on an EDV vaccine in humans No information on human trials. An early trial of an EVD vaccine containing two EVD strains (Zaire & Sudan) started in Sep 2014 in the USA. A vaccine against the Zaire strain may be evaluated in the UK and then in two African countries this month. The earliest availability depends on results of the trial and manufacturing timelines. Approximately 15,000 doses might be available by the end of 2014 Recombinant vesicular stomatitis virus (rVSV) vaccine Aims to induce EVD-specific immune responses. A single does of the vaccine given one month in advance protected 16/16 animals from lethal dose. Animals with weak immunity were not harmed. Was safe when directly injected into the brain of the animal. It is unknown is rVSV will grow in humans, especially with weak immunity. Too little growth could make a weak vaccine, while too much could cause illness or possible spread to unvaccinated people or animals. One lab worker was given rVSV after a needle stick injury and remained well. The lab worker had a small but detectable amount of vaccine in plasma for a short time after vaccination. Safety, efficacy, and duration of protection are unknown. A trial is due to start soon in the USA. Currently, 800 doses are available and more is in production Treatment Modalities: Therapeutics Several investigational therapeutics for Ebola virus disease are in development… Treatment Modalities: Therapeutics Available or Under Development Therapy How does it work State of Research Safety in Humans Availability Convalescent plasma Studies Blood transfusions from EVD survivors might prevent or treat Ebola virus infection in others, but the results of the studies are still difficult to interpret It is not known whether antibodies in the plasma of survivors are sufficient to treat or prevent the disease. More research is needed. Safe if provided by well-managed blood banks. Risks are like those associated with the use of any blood products, such as the transmission of blood-borne pathogens that cause disease. There is a theoretical concern about antibody- dependent enhancement of EVD infection, which can increase infectivity in the cells. Transfusion is culturally acceptable in West Africa. Potential donors are Ebola survivors, but the logistics of blood collection are an issue. Options to conduct studies in patients are being explored. The first batches of convalescent plasma might be available by the end of 2014. ZMapp Cocktail of three chimeric mouse- human monoclonal antibodies (Mapp Biopharmaceutical Inc.) The three antibodies in this mixture block or neutralize the virus by binding to or coating a different site on the covering or “envelope” of the virus. Studies in non human primates (NHPs) showed a strong survival up to five days after infection, when virus and/or fever were present. There have been no formal safety studies in humans. Very small numbers of EVDinfected people have been given ZMapp on a compassionate basis and no safety issues have been reported to date. Clinical effectiveness is still uncertain A very limited supply (fewer than 10 treatment courses) has been deployed to the field. At the date of publication of this revised document no doses remain. Efforts to scale up production may yield increased supplies of potentially few hundred doses by the end of 2014. Treatment Modalities: Therapeutics Available or Under Development Vaccine Type How does it work State of Research Safety in Humans Availability Hyperimmune globulin prepared by purifying and concentrating plasma of immunized animals or previously infected humans with high titres of neutralizing antibody against EVD Antibodies that can neutralize the different EVD strains have been produced shown to be protective in NHPs when treatment begins 48 hours after exposure to EVD. Generally safe. There has been extensive experience with the use of hyperimmune globulin against other infectious agents in humans. Inactivation and purification procedures effectively eliminate blood-borne pathogens that cause disease. Not currently available. Several months are needed to immunize animals, collect plasma, and make the purified product. Work is starting on the production of immune globulin in horses and of human immune globulin in cattle. Studies in horses could take place within six months, but largescale batches for use in humans TKM-100802 Lipid nanoparticle small interfering Ribonucleic acid (siRNA) (Tekmira These target two essential viral genes to stop the virus from replicating Effective in guinea pigs and monkeys. In NHPs, there is an 83% survival rate, if administered 48 hours after infection and 67% survival 72 hours after infection. A single-dose study in healthy volunteers found side effects include headache, dizziness, chest tightness, and increased heart rate at high doses. At lower doses, projected to be the dose used for treatment, the drug was better tolerated. The US Food and Drug Administration (FDA) has authorized emergency use in EVDinfected patients and several such patients have received treatment with this product. A limited number of treatment courses (15-20) are available. There is potential for the production of up to 900 courses by early 2015. Treatment Modalities: Therapeutics Available or Under Development Vaccine Type How does it work State of Research Safety in Humans Availability AVI 7537 (Sarepta) Phosphorodiamidate oligonucleotide In NHP studies, doses of 14 to 40 mg/kg for 14 days showed typical survival ranging from 60% to 80% when given at the time of infection. Human tolerability has been demonstrated in early studies The active pharmaceutical ingredient is available for 20-25 courses by mid-October 2014. Potential production of approximately 100 treatment courses by early 2015. Favipivavir/T-705 (Toyama Chemical/Fuji Film This has shown effectiveness against EVD in mice, but in a NHP study only one out of six survived. Another study of animals using a different dose regimen is underway Approved in Japan for influenza treatment under special circumstances. Remains under study in other countries. Has been tested in more than 1 000 people, with no major adverse effects reported. But the dose proposed for treatment of EVD could be 2-5 times higher than that tested so far and duration of treatment might be longer than in current influenza studies. It should not be used during pregnancy due to potential birth defects. It has not been studied in humans for Ebola. Use for field post-exposure prophylaxis is under discussion. More than 10,000 treatment courses may be available, pending determination of the dose for treatment of EVD. Future supply is not limited. Treatment Modalities: Therapeutics Available or Under Development Vaccine Type How does it work BCX4430 (Biocryst) Interferons Induces an antiviral state in exposed cells and regulates the immune system. State of Research Safety in Humans Availability Studies of this antiviral in animals indicate 83% to 100% survival in rodents with EVD. It is also effective in animals 48 hours after infection with the lethal Marburg virus, which belongs to the same family as Ebola. Testing for EVD in NHPs is underway. No human safety studies or data available. Safety studies are planned Needs NHP protection data for EVD before it can be considered. No material is currently available for field use. A study showed delayed time to death in NHPs but no overall increased survival. Early administration enhances the effectiveness of treatment in animals and lengthens the time after the viral infection at which antibodies show effectiveness. Various forms approved for treating chronic hepatitis and multiple sclerosis. Higher doses are associated with increased adverse effects but no greater efficacy. Commercially available. There are several types of interferons. Decisions regarding which one to use, when to use, and the dose regimen need careful consideration Prevention If you travel to or are in an area affected by an Ebola outbreak, make sure to do the following: • • • • • • Practice careful hygiene. For example, wash your hands with soap and water or an alcohol-based hand sanitizer and avoid contact with blood and body fluids. Do not handle items that may have come in contact with an infected person’s blood or body fluids (such as clothes, bedding, needles, and medical equipment). Avoid funeral or burial rituals that require handling the body of someone who has died from Ebola. Avoid contact with bats and nonhuman primates or blood, fluids, and raw meat prepared from these animals. Avoid hospitals in West Africa where Ebola patients are being treated. The U.S. embassy or consulate is often able to provide advice on facilities. After you return, monitor your health for 21 days and seek medical care immediately if you develop symptoms of Ebola Prevention for HCWs Healthcare workers who may be exposed to people with Ebola should follow these steps: • • • • • • Wear appropriate PPE Practice proper infection control and sterilization measures Isolate patients with Ebola from other patients Avoid direct contact with the bodies of people who have died from Ebola Notify health officials if you have had direct contact with the blood or body fluids, such as but not limited to, feces, saliva, urine, vomit, and semen of a person who is sick with Ebola The virus can enter the body through broken skin or unprotected mucous membranes in, for example, the eyes, nose, or mouth. Discussion • The 2014 Ebola Virus Disease (EVD, or “Ebola”) outbreak is the largest and most complex Ebola outbreak on record, with an unprecedented number of affected countries, thousands of cases and deaths in the general population, and hundreds of infected health care workers • The escalating scale and mortality of the outbreak has reinforced the urgent need for the accelerated development and availability of specific effective medical interventions for EVD • Subject to the outcome of initial safety and immunogenicity trials – expected in December 2014 - Ebola vaccine may be available for efficacy trials and large-scale use during the first months of 2015 • Predictions of up to 10,000 cases per week expected starting December if disease not contained. Discussion: Global Response • US Response: • • Ebola Czar was appointed by President Obama A 30-member U.S. military team that could be called on to respond to new cases of Ebola in the United States started specialized training at Fort Sam Houston in Texas. • • • • • The weeklong training includes infection control and how to use personal protective gear Paul Allen foundation pledged $100 USD million Bill Gates, pledged $50 million USD through his foundation Mark Zuckerberg, added $25 million USD to the Centers for Disease Control and Prevention Foundation coffers to help buy personal protective equipment, ready-to-eat meals, generators, vehicles and motorcycles, and thermal scanners to detect fever These donations are in addition to the US government spending and sending 3,000 troops, supplies and expertise to the affected area. Discussion: Global Response • The EU pledged to increase its aid to help fight Ebola by $380 million to $1.2 billion • China pledged to boost its aid to the three West African nations fighting the Ebola outbreak • • The Chinese government will provide a fourth round of assistance to Liberia, Sierra Leone and Guinea that will include emergency funding and supplies worth the equivalent of $82 million China will also dispatch quarantine experts and medical personnel, and it will set up a new treatment center in Liberia. Discussion: Countries Donations in US Dollars (Tracked by the UN) Discussion: NGOs, Corporation & International Institutions Donations in US Dollars (Tracked by the UN) Discussion: Needed Funds • • • • WHO requires $US 260 million to meet the objectives of its response to the Ebola outbreak in the affected areas To date, WHO has received 49% of those funds, while 15% of the funds required have been pledged This leaves a gap of 36% of the funds needed WHO continues to appeal to Member States to provide funding and other resources to assist in containing the Ebola outbreak. Discussion: NIH Funding as a Share of GDP, FY 1950-2019 Source: Erosion of Funding for the National Institutes of Health Threatens U.S. Leadership in Biomedical Research , Center for American Progress Discussion: NIH Funding • NIH-funded biomedical research has played a critical role in improving the physical and mental health of Americans, which in turn has yielded significant societal economic benefits • Federal funding has turned NIH into the cornerstone of an American biomedical research sector that leads the world in investment and innovation • NIH budgets began stagnating after 2003 and declining in 2010, the costs of conducting biomedical research continued to rapidly increase • This was further hurt by recent budgetary cuts and sequestration • In order to secure America’s position as the global leader in biomedical research for the foreseeable future, Congress must pursue significant new investments. Discussion: Travel Travel Restrictions • No evidence that travel bans have been effective in limiting the spread of infectious disease Three-week monitoring for some travelers • All travelers coming to the United States from Ebolaaffected areas will be actively monitored for 21 days. Also, all U.S.-bound passengers from Liberia, Sierra Leone and Guinea must land in one of the five U.S. airports with enhanced screening for Ebola: 1. 2. 3. 4. 5. New York's John F. Kennedy International, Washington Dulles, New Jersey's Newark Liberty International, Chicago's O'Hare International and Hartsfield-Jackson International in Atlanta. Beds Needed: What is being done? • • • Preliminary Analysis Existing ETC Beds Required ETC Beds Existing ETC Beds (%) Guinea 160 260 61% Liberia 620 2690 23% Sierra Leone 346 1198 29% Around 150 local construction workers have been working 3 shifts a day to build an Ebola treatment center (ETC) at the former Ministry of Defense compound on the outskirts of Monrovia. The 6 large tents, that can house 50 patients each, are now in place and the center is set to open at the end of October. This will add at least 200 additional beds for Ebola patients in Liberia. Latest data indicate that 22% of 4,707 planned ETC beds and 4% of 2,685 planned Community Care Center (CCC) beds are now in operation. • • • A health-care partner has already been identified for the construction of 2,110 beds, accounting for 58% of the gap between planned and existing ETC beds. Another 1,550 beds remain at the planning stage, without an identified health-care partner. Efforts are being made by WHO to identify partners to construct, supervise and operate ETC and CCC beds. Discussion: Critical Questions to Address • Who should be vaccinated as a priority? • How much vaccine will there be and by when? • How and when will we know that the vaccines “work”? • Who will finance vaccines and vaccination campaigns? Discussion: WHO Vaccine Development Meeting Summary • Impact: Vaccines will have a significant impact on the further evolution of the epidemic in any scenario, from best-case to worst-case • Financing: Funding issues should not be allowed to dictate the vaccine agenda. The funds will be found • Liability: Neither affected countries nor industry should be left alone to bear the burden should lawsuits arise following possible adverse reactions to an Ebola vaccine. Establish a “club” of donors, in collaboration with the World Bank • Timing & Quantity: Timing and quantity of vaccine doses should not constrain the design of clinical trials. Industry confirms that enough vaccine doses would be available • GlaxoSmithKline’s monthly production capacity for purified bulk vaccine was expected to rise from the current figure of 24,000 doses to 230,000 by April 2015, if they can be filled for release • NewLink’s bulk vaccine manufacturing capacity for the Canadian vaccine was noted to vary, according to the dose selected, from 52,000 doses to 5.2 million doses anticipated for the first quarter of 2015 • Priority: Health care workers, including medical staff, laboratory staff, burial teams, and facility cleaners, should have first call on vaccine doses while supplies remain limited • Vaccination of health care workers in the three countries is feasible during the first quarter of 2015. Conclusion The World is “making this up” as we go and we have to become more comfortable with uncertainty The current epidemic in West Africa which struggled to meet the basic healthcare needs of populations has made it impossible to managing acute care for Ebola patients The first focus needs to be on relatively simple things to decrease mortality in West Africa. Data suggest aggressive intravenous hydration, replacing electrolytes, managing nausea, fever, and superimposed bacterial infection are relatively inexpensive measures that can be part of the bundle of care There is a critical need for ETC & CCC beds in the three most affected countries Proper training and protective gear needs to be provided to the hospital staff taking care of EVD cases & burial staff dealing with corpses is critical Behavioral changes that increase exposure to infected animals needs to be modified Complex ethical challenges abound related to the use of untested interventions, quarantines, special care, and other issues Conclusion There is no evidence that travel bans have been effective in limiting the spread of infectious disease in any previous infectious disease outbreak and it is unlikely that any such ban on Ebola-infected countries will limit the spread of Ebola • Post-Arrival in the US 21 Day self-quarantine • • • • • Attention should be on how best to help Ebola-infected countries where the outbreak is raging rather than spending any human or financial resources required to enforce a travel ban Is not only be ethically permissible, but even ethically obligatory Ethically, 'right conditions' are key; the well-being of the quarantined person must be guaranteed People in quarantine need to be provided the resources to maintain as decent a quality of life as possible Above all they need to be treated with respect They need to feel secure that their needs and the needs of their family will be met and that they will have reliable and regular access to appropriate information about any ill loved ones, as well as their own risks Airlift foreign health workers • Yes, this should be ethically acceptable • We must make special commitments to the healthcare providers who are willing to serve • In this outbreak, these people agreed to help out in an epidemic that has a very high mortality rate. These doctors and nurses, must be promised not only high quality training and protective equipment going forward, but also that if something happens, we must take care of them • Someone must take care of the heroes who are volunteering to take care of people in West Africa, and within a very challenging context; they absolutely must be guaranteed first-rate treatment should they become sick. Although there are signs that the epidemic is slowing down in some areas, if not met with an effective and sustainable international response it will case much more devastation in West Africa A safe & efficacious vaccine is the only hope of containing the outbreak but characterized the U.S. investment in vaccine research is "a drop in the bucket” A non-patrician effort in the US is needed to increase funding support to NIH and DOD for R&D and Advanced Development of Vaccines, Therapeutics and Diagnostics as well as Manufacturing Facilities for diseases such as Ebola and other infectious diseases Countries, NGO’s and Funding Agencies (Private or Public) need to fulfill their pledges as soon as possible. !!!!Remember diseases do not observe boundaries!!!!