Materiały źródłowe

• #1 Recent advances in the treatment of Ebola disease: A brief overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10942026/

  Ebola disease (EBOD) remains a significant and ongoing threat to African countries, characterized by a mortality rate of 25% to 90% in patients with high viral load and significant transmissibility. […] Since its discovery in 1976, the management of EBOD has primarily relied on supportive care. […] Following the devastating outbreak in West Africa from 2014 to 2016 secondary to the Zaire Ebola virus (EBOV), where over 28,000 lives were lost, dedicated efforts to find effective therapeutic agents have resulted in considerable progress in treating and preventing disease secondary to EBOV. Notably, 2 monoclonal antibodies Ebanga and a cocktail of monoclonal antibodies, called Inmazeb received Food and Drug Administration (FDA) approval in 2020. […] This review covers the key signs and symptoms of EBOD, its modes of transmission, and the principles guiding supportive care. Furthermore, it explores recent advancements in treating and preventing EBOD, highlighting the unique properties of each therapeutic agent and the ongoing progress in discovering new treatments.

• #1 Clinical Guidance for Ebola Disease | Ebola | CDC

  https://www.cdc.gov/ebola/hcp/clinical-guidance/index.html

  Clinical management of patients with Ebola disease should focus on supportive care for complications, such as hypovolemia, electrolyte abnormalities, hematologic abnormalities, refractory shock, hypoxia, hemorrhage, septic shock, multiorgan failure, and disseminated intravascular coagulation (DIC). […] Recommended care includes volume repletion, maintenance of blood pressure (with vasopressors if needed), and maintenance of oxygenation, pain control, nutritional support, and treatment of secondary bacterial infections and pre-existing comorbidities. […] Large volumes of intravenous fluids are often required to correct dehydration due to diarrhea and vomiting. Some patients may develop profound third-spacing of fluids due to vascular leak.

• #1 Ebola disease – Management Approach | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1210/management-approach

  It is now clear that full supportive care can reduce mortality, with a reported survival rate of 81.5% in patients managed outside the West African setting, and that it should be provided whenever possible. […] Individualized and optimized supportive care is recommended for all patients. […] Systematic assessment and reassessment of patients. […] Fluid resuscitation. […] Electrolyte monitoring and correction. […] Glucose monitoring and management. […] Management of potential co-infections. […] Nutrition. […] Symptomatic care. […] Prevention and management of complications. […] The high frequency of vomiting and diarrhea means that patients are often dehydrated and hypovolemic, particularly if they present late. […] Oral rehydration solutions can be used for patients who can tolerate oral administration and who are not severely dehydrated, but the majority of patients require intravenous fluid replacement with either normal saline or lactated Ringer solution.

• #1

  https://link.springer.com/article/10.1007/s00134-020-05949-z

  With specific anti-Ebola medications, most patients can survive Ebola virus infection. […] Treatment has shifted from a focus upon isolation and oral rehydration (minimal-touch) to one of optimized care involving rapid diagnostic testing, frequent or continuous monitoring of vital signs, individualized enteral and intravenous fluid treatment, intravenous vasoactive medications, supplemental oxygen, occasional mechanical ventilation, renal replacement therapy and now, specific and effective antiviral therapies. […] In this review, we highlight the need for clinicians to be able to recognize and manage Ebola-related organ dysfunction, and highlight that advanced supportive care is necessary of treatment for severely ill patients with EVD. […] Basic supportive care recommendations include: systematic monitoring and documentation of clinical signs and symptoms; a clinician to patient ratio of 1:4 but with emphasis placed on maximizing patient contact time; patient-family audio-visual communication; psychosocial care; provision of oral rehydration therapy to correct or prevent hypovolemia; parenteral fluids for patients unable to achieve sufficient enteral hydration; measurement of serum biochemistry with correction of identified electrolyte abnormalities; oxygen administration to achieve normal oxygen saturation; intravenous vasoactive medications for patients with fluid-resistant hypotension and organ hypoperfusion; pain management, antiemetics, and anxiolytics; nutritional support customized to patient assessment including treatment of hypoglycemia with intravenous glucose when necessary; and microbiological analysis to guide antimicrobial use, and in absence of such capacity, a low threshold for empirical use of broad-spectrum antibiotics and antimalarials, depending on the geographical context and symptoms.

• #1 Clinical Guidance for Ebola Disease | Ebola | CDC

  https://www.cdc.gov/ebola/hcp/clinical-guidance/index.html

  FDA-approved treatments for Ebola infection are available. […] Two treatments are approved by the U.S. Food and Drug Administration (FDA) to treat Ebola disease caused by Ebola virus (species Zaire orthoebolavirus). Inmazeb is a combination of three monoclonal antibodies and Ebanga is a single monoclonal antibody. Monoclonal antibodies, or mAbs, are artificially produced antibodies that act like natural antibodies to stop the virus from replicating in a person’s body. These mAbs bind to a portion of the virus called the glycoprotein and prevent the virus from entering the person’s cells. […] Both treatments were evaluated, along with two others, in a randomized controlled trial in the Democratic Republic of the Congo. Overall survival was higher for patients who received either Inmazeb or Ebanga. The efficacy of these treatments has not been established for viruses other than Ebola virus (species Zaire orthoebolavirus).

• #1 FDA Approves First Treatment for Ebola Virus | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-ebola-virus

  Today, the U.S. Food and Drug Administration approved Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn), a mixture of three monoclonal antibodies, as the first FDA-approved treatment for Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients. […] Inmazeb targets the glycoprotein that is on the surface of Ebola virus. Glycoprotein attaches to the cell receptor and fuses the viral and host cell membranes allowing the virus to enter the cell. The three antibodies that make up Inmazeb can bind to this glycoprotein simultaneously and block attachment and entry of the virus. […] In the PALM trial, the safety and efficacy of Inmazeb was evaluated in a multi-center, open-label, randomized controlled trial, in which 154 patients received Inmazeb (50 mg of each monoclonal antibody) intravenously as a single infusion, and 168 patients received an investigational control. The primary efficacy endpoint was 28-day mortality. The primary analysis population was all patients who were randomized and concurrently eligible to receive either Inmazeb or the investigational control during the same time period of the trial. Of the 154 patients who received Inmazeb, 33.8% died after 28 days, compared to 51% of the 153 patients who received a control. In the expanded access program, an additional 228 patients received Inmazeb.

• #1 Ebola | FDA

  https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/ebola

  Ebola virus disease (EVD) is a rare and deadly disease in people and nonhuman primates. […] The FDA is working to help expedite the development and availability of medical products such as treatments, vaccines, diagnostic tests, and personal protective equipment with the potential to help bring Ebola outbreaks under control as quickly as possible. […] There are currently two treatments approved by the FDA to treat EVD caused by Zaire ebolavirus in adults and children. […] On December 21, 2020, the FDA approved Ebanga (Ansuvimab-zykl), a human monoclonal antibody, for the treatment for Zaire ebolavirus (Ebola virus) infection in adults and children. […] On October 14, 2020, the FDA announced the approval of Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn), a mixture of three monoclonal antibodies, as the first FDA-approved treatment for Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients. […] Learn more about Ebola treatment from CDC, including information for clinicians.

• #1 Ebola explained: Symptoms, treatment and vaccines – DW – 02/06/2025

  https://www.dw.com/en/ebola-symptoms-treatment-vaccines-sudan-virus/a-71524627

  Ebola virus disease (EVD) — named after the river — is the deadliest form of the virus. It has a survival rate of 10% of cases. […] If caught early, hospital treatment, with oral and intravenous fluids and medicines, can help and reduce the risk of fatality. […] One such medicine is Ebanga — an antibody-based drug that prevents the virus from entering cells, thus slowing its spread through the body. […] A second drug is Inmazeb — a cocktail of three antibodies. […] The World Health Organization (WHO) advises against treating people at home, especially without the help of professional health care. The virus is highly contagious and other people in the home will likely get sick. […] Other treatments include blood transfusions, medicines to treat the symptoms — pain, nausea, vomiting and diarrhea — or coexisting illnesses, such as malaria.

• #1 Recent advances in the treatment of Ebola disease: A brief overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10942026/

  Supportive care and treatment of complications are the cornerstones of the treatment of EBOD. […] Intensive care unit admission may be required in up to 50% of admitted patients with EBOD for close monitoring, respiratory support, and management of severe complications. […] Most expert opinions recommend empirical broad-spectrum antibiotics in critically ill EBOD patients since reports have indicated a higher susceptibility to bacterial infection. […] Currently, there are 2 Food and Drug Administration (FDA)-approved agents for the treatment of EVD: atoltivimab-maftivimab-odesivimab (Inmazeb) and ansuvimab (Ebanga), both receiving FDA approval in October and December 2020, respectively. […] The efficacy of Ebanga and Inmazeb has been demonstrated in the PALM trial, conducted during the 2018 to 2020 North-Kivu and Ituri epidemics. […] Significant progress has been made in EVD treatment and prevention, but many questions remain unanswered.

• #1 Marburg and Ebola Virus Infections – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/arboviruses-arenaviridae-and-filoviridae/marburg-and-ebola-virus-infections

  Treatment of Marburg and Ebola Virus Infections includes supportive care and antiviral therapy. Supportive care includes the following: Maintenance of blood volume and electrolyte balance, Replacement of depleted coagulation factors, Minimization of invasive procedures, Treatment of symptoms, including use of analgesics. Two monoclonal antibody treatments are currently available to treat Ebola virus infection caused by the Zaire ebolavirus. These are REGN-EB3 and mAb114. REGN-EB3 was approved by the US Food and Drug Administration (FDA) in October 2020 and is a combination of three monoclonal antibodies (atoltivimab/maftivimab/odesivimab). The second medication, mAb114, is a single monoclonal antibody (ansuvimab) that was approved in December 2020. Both of these treatments were proven effective during the 2018 to 2020 Ebola outbreak in the DRC demonstrating cure rates of about 90% in patients with low viral loads (which suggests treatment was begun within the first few days after infection). This is compared to a death rate that is thought to be over 70% in untreated and unvaccinated patients and is a significant improvement over previous experimental medications for Ebola (ZMapp, remdesivir). […] Until the two monoclonal antibodies or others are shown to neutralize Marburg virus, there is still no effective treatment for that virus infection.

• #1

  https://www.who.int/news/item/19-08-2022-who-makes-new-recommendations-for-ebola-treatments—–calls-for-improved-access

  The World Health Organization (WHO) has published its first guideline for Ebola virus disease therapeutics, with new strong recommendations for the use of two monoclonal antibodies. […] WHO has made strong recommendations for two monoclonal antibody treatments: mAb114 (Ansuvimab; Ebanga) and REGN-EB3 (Inmazeb). […] The two recommended therapeutics have demonstrated clear benefits and therefore can be used for all patients confirmed positive for Ebola virus disease, including older people, pregnant and breastfeeding women, children and newborns born to mothers with confirmed Ebola within the first 7 days after birth. Patients should receive recommended neutralizing monoclonal antibodies as soon as possible after laboratory confirmation of diagnosis. […] There is also a recommendation on therapeutics that should not be used to treat patients: these include ZMapp and remdesivir.

• #1 Ebola Virus Infection Treatment & Management: Approach Considerations, Supportive Care, Pharmacologic Therapy

  https://emedicine.medscape.com/article/216288-treatment

  The focus of mAb research is now shifting toward treatment of established infection. […] The recombinant monoclonal antibody combination atoltivimab/maftivimab/odesivimab (Inmazeb; REGN-EB3) is the first treatment for Zaire ebolavirus and was approved by the US Food and Drug Administration (FDA) in October 2020. […] Another recombinant human monoclonal antibody, ansuvimab (Ebanga) was FDA-approved in December 2020. It also is indicated for treatment of Orthoebolavirus zairense (formerly Zaire ebolavirus) infection in adults and children, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection. […] Limitations of use for atoltivimab/maftivimab/odesivimab and ansuvimab include the following: The effectiveness of the treatment has not been confirmed for other species within the Orthoebolavirus and Orthomarburgvirus genera. […] Both approvals were based on results from the PALM trial (n = 681).

• #1 FDA Approves First Treatment for Ebola Virus | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-ebola-virus

  Patients who receive Inmazeb should avoid the concurrent administration of a live vaccine due to the treatments potential to inhibit replication of a live vaccine virus indicated for prevention of Ebola virus infection and possibly reduce the vaccines efficacy. […] Inmazeb received an Orphan Drug designation for the treatment of Ebola virus infection. The Orphan Drug designation provides incentives to assist and encourage drug development for rare diseases. Additionally, the agency granted Inmazeb a Breakthrough Therapy designation for the treatment of Zaire ebolavirus infection.

• #1

  https://www.who.int/news/item/19-08-2022-who-makes-new-recommendations-for-ebola-treatments—–calls-for-improved-access

  Advances in supportive care and therapeutics over the past decade have revolutionized the treatment of Ebola. […] Provision of best supportive medical care to patients, combined with monoclonal antibody treatment MAb114 or REGN-EB3 now leads to recovery for the vast majority of people. […] Although WHO was able to make strong recommendations for the use of two therapeutics, there is a need for further research and evaluation of clinical interventions, as many uncertainties remain.

• #1 Updates on Treatment of Ebola Virus Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5295760/

  Michelow et al. proposed that recombinant human Mannose Binding Lectin (rhMBL) therapy can be used as a novel broad spectrum antiviral approach for treating Ebola patients. Some experimental strategies that have shown promising results in treating EBOV-challenged non-human primates (NHPs) after Ebola infection are: i) recombinant human activated protein C (rhAPC); ii) recombinant nematode anticoagulant protein c2 (rNAPc2); iii) small interfering RNA (siRNA); iv) positively-charged phosphorodiamidatemorpholino oligomers (PMOplus); and v) ZMAb (consisting of murine mAbs m1H3, m2G4, and m4G7). Follow-up studies found that ZMAb combined with an adenovirus-based adjuvant may help provide full protection in rhesus macaques when treatment was administered up to 72 h after infection. […] ZMapp is a humanised monoclonal antibody that targets the EBOV glycoprotein. This drug was first used in the 2014 West Africa Ebola virus outbreak and is currently in phase II clinical trials. To date, the safety and efficacy of ZMapp has not yet been fully demonstrated and thus the drug is not yet licensed. Drugs such as Zmapp can have several side effects, including fever, nausea, vomiting, diarrhoea, rashes, and in rare cases, life-threatening shock. The nucleotide analogue favipiravir and siRNA TKM 100802 are two other antiviral drugs that were approved for emergency use during EBOV outbreaks. These drugs are currently in phase II and III clinical trials. Favipiravir is proposed to be safe when taken orally and shows rapid distribution and uptake in cases arising during inhalational EBOV outbreaks. The peptide FX06 and monoclonal antibody mixture ZMab as well as several other drugs are currently being administered on a compassionate basis as the safety and efficacy of these drugs in patients is still undergoing evaluation.

• #1 Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea | PLOS Medicine

  https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001967

  Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. […] Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. […] Favipiravir was well tolerated. […] The trial could not answer definitively whether favipiravir treatment was safe or reduced mortality in patients with EVD. The results suggest that the drug is unlikely to be beneficial for patients with very high viral loads, at least when given by itself. They also suggest that favipiravir is safe in patients with lower viral loads, and that in such patients additional efficacy studies are warranted.

• #1

  https://link.springer.com/article/10.1007/s40121-023-00913-y

  There is a strong recommendation for treatment with either mAb114 or REGN-EB3 for patients with RT-qPCR-confirmed EVD and neonates of unconfirmed EVD status, 7 days or younger, born to mothers with confirmed EVD. […] The use of these medicines does not replace optimized supportive care, and they should be administered as soon as possible after diagnosis. […] There are conditional recommendations against treatment with remdesivir or Zmapp for patients with RT-qPCR-confirmed EVD because of considerable uncertainty of mortality reduction compared with the standard of care. […] Despite the improvements in EVD therapy over the previous few years, deaths in the PALM study were nevertheless accounted for by 35.1% (61/174) and 33.5% (52/155) of people receiving the mAb114 and REGN-EB3 therapies, respectively.

• #1 Immunological Perspective for Ebola Virus Infection and Various Treatment Measures Taken to Fight the Disease

  https://www.mdpi.com/2076-0817/9/10/850

  Currently, despite the encouraging news on the vaccine approval, there is a long way to complete, global protection against future EBOV outbreaks. […] The therapeutic efficacy of the small RNA (sRNA) molecules was also tested using NHP model of EBOV infection. TKM-100802, a small RNA-interfering (siRNA) molecule targeting VP35 and L genes, was administered to NHP 30 min prior EBOV infection. […] Remdesivir or GS-5734 had 100% protection in NHP when administered 72 h post EBOV infection. […] Monoclonal antibodies (mAb) are IgG antibodies produced by a single B cell clone that could help to control virus spread by targeting EBOV GP. […] ZMapp, an antibody cocktail, is product of collaboration between US Mapp Biopharmaceutical, Inc. and Defyrus, Inc. This cocktail consists of the best mAb amongst the individual monoclonal antibodies which are present in Mab-003 and ZMAb.

• #1 Updates on Treatment of Ebola Virus Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5295760/

  Ebola viral disease is one of the major threats world wide. But the treatment option is merely supportive and symptomatic therapy. Vaccination and drug therapies are still under trial. This article throws light into the various emerging treatment options for the Ebola viral disease. […] Unfortunately, management of Ebola outbreaks is limited to palliative care and preventive measures. Supportive treatments include fluid resuscitation, correcting electrolyte imbalances, and treating secondary infections. Blood transfusion therapy, immunological therapy, drug therapies, and vaccines are all currently under development. This article discusses several approaches to treat Ebola virus (EBOV) infections that are currently being explored. […] Some animal model data suggest that hyperimmune intravenous immunoglobulin preparations fractionated from reconvalescent plasma could be used as an Ebola treatment because this blood contains antibodies against EBOV. Treatment strategies using reconvalescent plasma are currently undergoing Phase II and III clinical trials. Comparisons of the efficacy of whole blood and plasma transfusions suggest that plasma transfusion is the preferable approach.

• #1 Research in management of Ebola – Wikipedia

  https://en.wikipedia.org/wiki/Research_in_management_of_Ebola

  There is a cure for the Ebola virus disease that is currently approved for market the US government has inventory in the Strategic National Stockpile. […] As of August 2023, treatment known as atoltivimab/maftivimab/odesivimab and experimental ansuvimab were found to be 90% effective. […] In October 2020, the U.S. Food and Drug Administration (FDA) approved atoltivimab/maftivimab/odesivimab with an indication for the treatment of infection caused by Zaire ebolavirus. […] The World Health Organization (WHO) has stated that transfusion of whole blood or purified serum from Ebola survivors has the greatest potential to be implemented immediately, and has issued an interim guideline for this therapy. […] A study in Sierra Leone started in November 2014, and preliminary results show an 80 percent survival rate.

• #1 Research in management of Ebola – Wikipedia

  https://en.wikipedia.org/wiki/Research_in_management_of_Ebola

  Trials in Liberia and Guinea started in January 2015, with funding from the Gates Foundation. […] Ribavirin is also known to be ineffective against ebolaviruses despite its effectiveness against other viral hemorrhagic fevers such as Lassa fever. […] Interferon therapies have been tried as a form of treatment for EVD, but were found to be ineffective. […] The Hemopurifier is a single-use disposable biological cartridge designed for use with dialysis machines and other blood circulatory pumps. It is a method for removal of viruses from blood by lectin affinity hemodialysis which embodies reducing viral loads in the blood of individuals infected with a virus. […] During October 2014, the Hemopurifier was used as an adjunct in the treatment of a patient with Ebola, who then recovered.

• #1 Ebola disease – Management Approach | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1210/management-approach

  Close supervision and frequent monitoring are required as it is important to assess response and prevent fluid overload. […] WHO guidelines should be consulted for specific recommendations on fluid and electrolyte management as well as on maintaining adequate nutrition during acute illness and the convalescent phase. […] Therapeutic antiviral monoclonal antibodies are available. The WHO strongly recommends either atoltivimab/maftivimab/odesivimab (also known as REGN-EB3) or ansuvimab (also known as mAb114) for patients with confirmed infection with Ebola virus. […] Malaria should be tested for and treated with appropriate antimalarial therapy if present while keeping in mind the patient’s risk for Ebola disease and the possibility of a dual infection. […] The WHO recommends the following key management principles: Use both standard precautions and Ebola-specific infection prevention and control measures. Include optimized supportive care in the clinical management of all pregnant women.

• #1 Ebola Virus Disease – PAHO/WHO | Pan American Health Organization

  https://www.paho.org/en/topics/ebola-virus-disease

  Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever, is a rare but severe, often fatal illness in humans. […] Good outbreak control relies on applying a package of interventions, namely case management, infection prevention and control practices, surveillance and contact tracing, a good laboratory service, safe and dignified burials and social mobilization. […] Vaccines to protect against Ebola have been developed and have been used to help control the spread of Ebola outbreaks in Guinea and in the Democratic Republic of the Congo (DRC). […] Early supportive care with rehydration, symptomatic treatment improves survival. Two monoclonal antibodies (Inmazeb and Ebanga) were approved for the treatment of Zaire ebolavirus (Ebolavirus) infection in adults and children by the US Food and Drug Administration in late 2020. […] Pregnant and breastfeeding women with Ebola should be offered early supportive care. Likewise vaccine prevention and experimental treatment should be offered under the same conditions as for non-pregnant population.

• #1

  https://link.springer.com/article/10.1007/s40121-023-00913-y

  In 2022, the first evidence-based clinical practice guideline dedicated to specific therapies for EVD was published. […] Currently, two antibody-based therapeutics have received approval for treating Ebola virus disease (EVD). […] To further improve the outcomes of the disease it is crucial to focus on emerging therapeutics that may shift the grim course of the disease. […] Repurposing already approved drugs for non-EVD indications to treat EVD is a promising strategy to bypass some of the disadvantages associated with conventional drug discovery. […] The year 2022 was a breakthrough for EVD therapeutics. […] The WHO published an international guideline on 19 August 2022 with the most up-to-date recommendations for the clinical management of people with EVD. […] Following the PALM trial results, the two therapeutic mAbs were used for the treatment of EVD in the subsequent EBOV outbreaks under Expanded Access Programs (EAP), which corresponds to the emergency use of unapproved, investigational products outside of a clinical trial.

• #1 The Ebola virus can ‘hide out’ in the brain after treatment and cause recurrent infections

  https://theconversation.com/the-ebola-virus-can-hide-out-in-the-brain-after-treatment-and-cause-recurrent-infections-177721

  The Ebola virus can hide in the brains of monkeys that have recovered after medical treatment without causing symptoms and lead to recurrent infections, according to a study by a team I led that was published in the journal Science Translational Medicine. […] Treatment with monoclonal antibodies is the current standard of care for Ebola. But recurrent infections can occur even after apparently successful treatment, and patients can inadvertently transmit the virus and cause new outbreaks. […] Our work highlights the need to more deeply investigate why the Ebola virus persists in the brain. Because the brain is less accessible to monoclonal antibodies, treatments combining both monoclonal antibodies and antiviral drugs may help prevent and clear persistent Ebola infection and related disease in the brain.

• #1

  https://link.springer.com/article/10.1007/s00134-020-05949-z

  Supportive care remains the cornerstone of patient treatment. […] A number of direct acting anti-Ebola agents were proposed and evaluated during the West African Ebola outbreak. […] Health authorities and the WHO RD blueprint under the ethical framework of monitored emergency use of unregistered and investigational interventions (MEURI) recommended expanded access to investigational therapies, including three monoclonal antibodies (MAb114, ZMapp, and REGN-EB3) and one antiviral agent (remdesivir) in the 2018-2019 DRC Ebola outbreak. […] Management of patients with Ebola has evolved substantially over the past decade, from a clinical perspective of isolation and provision of oral rehydration therapy to one of treating the syndromic illness, specific patterns of organ dysfunction with oral and intravenous volume repletion, management of life-threatening electrolyte disturbances, support of renal dysfunction with dialysis, cardiovascular dysfunction with intravenous vasoactive medications, and oxygen and mechanical ventilation for respiratory failure.

• #2 Recent advances in the treatment of Ebola disease: A brief overview | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012038

  Ebola disease (EBOD) remains a significant and ongoing threat to African countries, characterized by a mortality rate of 25% to 90% in patients with high viral load and significant transmissibility. […] Since its discovery in 1976, the management of EBOD has primarily relied on supportive care. Following the devastating outbreak in West Africa from 2014 to 2016 secondary to the Zaire Ebola virus (EBOV), where over 28,000 lives were lost, dedicated efforts to find effective therapeutic agents have resulted in considerable progress in treating and preventing disease secondary to EBOV. Notably, 2 monoclonal antibodies Ebanga and a cocktail of monoclonal antibodies, called Inmazeb received Food and Drug Administration (FDA) approval in 2020. […] This review covers the key signs and symptoms of EBOD, its modes of transmission, and the principles guiding supportive care. Furthermore, it explores recent advancements in treating and preventing EBOD, highlighting the unique properties of each therapeutic agent and the ongoing progress in discovering new treatments.

• #2 Recent advances in the treatment of Ebola disease: A brief overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10942026/

  Supportive care and treatment of complications are the cornerstones of the treatment of EBOD. […] Intensive care unit admission may be required in up to 50% of admitted patients with EBOD for close monitoring, respiratory support, and management of severe complications. […] Most expert opinions recommend empirical broad-spectrum antibiotics in critically ill EBOD patients since reports have indicated a higher susceptibility to bacterial infection. […] Currently, there are 2 Food and Drug Administration (FDA)-approved agents for the treatment of EVD: atoltivimab-maftivimab-odesivimab (Inmazeb) and ansuvimab (Ebanga), both receiving FDA approval in October and December 2020, respectively. […] The efficacy of Ebanga and Inmazeb has been demonstrated in the PALM trial, conducted during the 2018 to 2020 North-Kivu and Ituri epidemics. […] Significant progress has been made in EVD treatment and prevention, but many questions remain unanswered.

• #2

  https://link.springer.com/article/10.1007/s00134-020-05949-z

  With specific anti-Ebola medications, most patients can survive Ebola virus infection. […] Treatment has shifted from a focus upon isolation and oral rehydration (minimal-touch) to one of optimized care involving rapid diagnostic testing, frequent or continuous monitoring of vital signs, individualized enteral and intravenous fluid treatment, intravenous vasoactive medications, supplemental oxygen, occasional mechanical ventilation, renal replacement therapy and now, specific and effective antiviral therapies. […] In this review, we highlight the need for clinicians to be able to recognize and manage Ebola-related organ dysfunction, and highlight that advanced supportive care is necessary of treatment for severely ill patients with EVD. […] Basic supportive care recommendations include: systematic monitoring and documentation of clinical signs and symptoms; a clinician to patient ratio of 1:4 but with emphasis placed on maximizing patient contact time; patient-family audio-visual communication; psychosocial care; provision of oral rehydration therapy to correct or prevent hypovolemia; parenteral fluids for patients unable to achieve sufficient enteral hydration; measurement of serum biochemistry with correction of identified electrolyte abnormalities; oxygen administration to achieve normal oxygen saturation; intravenous vasoactive medications for patients with fluid-resistant hypotension and organ hypoperfusion; pain management, antiemetics, and anxiolytics; nutritional support customized to patient assessment including treatment of hypoglycemia with intravenous glucose when necessary; and microbiological analysis to guide antimicrobial use, and in absence of such capacity, a low threshold for empirical use of broad-spectrum antibiotics and antimalarials, depending on the geographical context and symptoms.

• #2 Ebola virus disease Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/ebola-virus-disease

  There is no known cure for Ebola. Experimental treatments have been used, but none have been fully tested to see if they work well and are safe. […] People with Ebola must be treated in a hospital. There, they can be isolated so the disease cannot spread. Health care providers will treat the symptoms of the disease. […] Treatment for Ebola is supportive and includes: Fluids given through a vein (IV), Oxygen, Blood pressure management, Treatment for other infections, Blood transfusions. […] Survival depends on how a person’s immune system responds to the virus. A person also may be more likely to survive if they receive good medical care. […] People who survive Ebola are immune from the virus for 10 years or more. They can no longer spread Ebola. It is not known whether they can be infected with a different species of Ebola. However, men who survive can carry the Ebola virus in their sperm for as long as 3 months. They should abstain from sex or use condoms until their semen has tested negative for the virus. […] Long-term complications can include joint and vision problems.

• #2 Ebola disease – Management Approach | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1210/management-approach

  Close supervision and frequent monitoring are required as it is important to assess response and prevent fluid overload. […] WHO guidelines should be consulted for specific recommendations on fluid and electrolyte management as well as on maintaining adequate nutrition during acute illness and the convalescent phase. […] Therapeutic antiviral monoclonal antibodies are available. The WHO strongly recommends either atoltivimab/maftivimab/odesivimab (also known as REGN-EB3) or ansuvimab (also known as mAb114) for patients with confirmed infection with Ebola virus. […] Malaria should be tested for and treated with appropriate antimalarial therapy if present while keeping in mind the patient’s risk for Ebola disease and the possibility of a dual infection. […] The WHO recommends the following key management principles: Use both standard precautions and Ebola-specific infection prevention and control measures. Include optimized supportive care in the clinical management of all pregnant women.

• #2 Ebola | FDA

  https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/ebola

  Ebola virus disease (EVD) is a rare and deadly disease in people and nonhuman primates. […] The FDA is working to help expedite the development and availability of medical products such as treatments, vaccines, diagnostic tests, and personal protective equipment with the potential to help bring Ebola outbreaks under control as quickly as possible. […] There are currently two treatments approved by the FDA to treat EVD caused by Zaire ebolavirus in adults and children. […] On December 21, 2020, the FDA approved Ebanga (Ansuvimab-zykl), a human monoclonal antibody, for the treatment for Zaire ebolavirus (Ebola virus) infection in adults and children. […] On October 14, 2020, the FDA announced the approval of Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn), a mixture of three monoclonal antibodies, as the first FDA-approved treatment for Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients. […] Learn more about Ebola treatment from CDC, including information for clinicians.

• #2

  https://link.springer.com/article/10.1007/s40121-023-00913-y

  There is a strong recommendation for treatment with either mAb114 or REGN-EB3 for patients with RT-qPCR-confirmed EVD and neonates of unconfirmed EVD status, 7 days or younger, born to mothers with confirmed EVD. […] The use of these medicines does not replace optimized supportive care, and they should be administered as soon as possible after diagnosis. […] There are conditional recommendations against treatment with remdesivir or Zmapp for patients with RT-qPCR-confirmed EVD because of considerable uncertainty of mortality reduction compared with the standard of care. […] Despite the improvements in EVD therapy over the previous few years, deaths in the PALM study were nevertheless accounted for by 35.1% (61/174) and 33.5% (52/155) of people receiving the mAb114 and REGN-EB3 therapies, respectively.

• #2 Ebola: Causes, Symptoms & Treatment | Live Science

  https://www.livescience.com/48311-ebola-causes-symptoms-treatment.html

  EVD is caused by viruses in the genus Ebolavirus within the family Filoviridae; these viruses most commonly cause disease in humans and nonhuman primates, including monkeys, gorillas and chimpanzees, according to the CDC. […] In 2020, the FDA approved two treatments for EVD caused by Zaire ebolavirus, according to the CDC. One, called Inmazeb, contains three monoclonal antibodies lab-made proteins that latch onto the virus and prevent it from infecting cells. The second treatment, Ebanga, contains a single monoclonal antibody that works the same way. […] Both treatments were tested during a clinical trial held during the 2018-2020 Ebola outbreak in the Democratic Republic of the Congo and were shown to increase patients’ chance of survival. (Neither treatment has been evaluated for efficacy against virus species other than Zaire ebolavirus.)

• #2

  https://www.gov.uk/government/publications/ebola-origins-reservoirs-transmission-and-guidelines/ebola-overview-history-origins-and-transmission

  EBOD patients require intensive supportive therapy, including intravenous fluids or oral rehydration with solutions including electrolytes as well as maintenance of oxygen status and blood pressure. […] Two monoclonal antibodies, REGN-EB3 (Inmazeb) and mAb114 (Ebanga) are available for the treatment of Ebola virus disease (EVD) caused by caused by the Ebola (Zaire) virus (EBOV). […] The WHOs Therapeutics for Ebola virus disease guidance recommends the use of REGN-EB3 and mAb114 for patients with laboratory confirmed EVD infection and for neonates 7 days old or younger with unconfirmed EVD status, who are born to mothers with confirmed EVD. […] There are currently no licensed therapeutics for the treatment of EBOD caused by orthoebolavirus sudanense (SUDV), or any of the other Ebolavirus species except EBOV.

• #2 Treatment for Ebola Virus Approved by FDA

  https://www.contagionlive.com/view/treatment-for-ebola-virus-approved-by-fda

  An Orphan Drug Designation was granted to Ridgeback Biotherapeutics, LP, creator the therapy. […] Ebanga, a human monoclonal antibody that treats Zaire ebolavirus (Ebolavirus), has been approved by the U.S. Food and Drug Administration for use in adults and children. The therapy blocks the binding of the virus to the cell receptor which prevents it from entering into the cell. […] Ebanga was evaluated in a clinical trial, called the PALM trial, that was led by the U.S. National Institutes of Health and the Institut National de Recherche Biomdicale, including many other international organizations and agencies during an Ebola outbreak in the Democratic Republic of the Congo in 2018-2019. […] During the multi-center, open-label, randomized controlled trial, Ebanga was evaluated for its levels of safety and efficacy. […] Those who plan on receiving Ebanga to treat an Ebolavirus infection should make sure to avoid a coinciding administration of a live virus vaccine, due to the potential for the therapy to impede on the replication of a live virus, which can potentially weaken the vaccines efficacy.

• #2 Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea | PLOS Medicine

  https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001967

  The results of the study indicate that monotherapy with favipiravir is unlikely to be effective in patients with very high viremia and merits further investigation in patients with intermediate to high viremia. […] Our study provided no evidence that favipiravir monotherapy at this dose might have a favorable benefit/risk ratio in patients with very high viral load. This does not prove that favipiravir could not provide a benefit in a person with very high viral load, but suggests that further studies in the same context will be very unlikely to show that monotherapy with favipiravir decreases mortality in patients with very high viral load. In contrast, in patients with a Ct 20 or a viral load below 108 genome copies/ml, future research on favipiravir monotherapy would be merited.

• #2 Immunological Perspective for Ebola Virus Infection and Various Treatment Measures Taken to Fight the Disease

  https://www.mdpi.com/2076-0817/9/10/850

  Currently, despite the encouraging news on the vaccine approval, there is a long way to complete, global protection against future EBOV outbreaks. […] The therapeutic efficacy of the small RNA (sRNA) molecules was also tested using NHP model of EBOV infection. TKM-100802, a small RNA-interfering (siRNA) molecule targeting VP35 and L genes, was administered to NHP 30 min prior EBOV infection. […] Remdesivir or GS-5734 had 100% protection in NHP when administered 72 h post EBOV infection. […] Monoclonal antibodies (mAb) are IgG antibodies produced by a single B cell clone that could help to control virus spread by targeting EBOV GP. […] ZMapp, an antibody cocktail, is product of collaboration between US Mapp Biopharmaceutical, Inc. and Defyrus, Inc. This cocktail consists of the best mAb amongst the individual monoclonal antibodies which are present in Mab-003 and ZMAb.

• #2 Treatment of Ebola Virus Disease: From Serotherapy to the Use of Monoclonal Antibodies

  https://www.mdpi.com/2073-4468/14/1/22

  MB-003 was one of the first drugs based on monoclonal antibodies to treat EVD. […] The ZMAb drug is very similar to the above one in the history of its creation and ideology. […] The protective effect of ZMAb was also studied in combination with DEF201. […] In 2014, the drug named Zmapp was created based on MB-003 and ZMAb components. […] Ebanga (or Ansuvimab) is the EBOV-neutralizing monoclonal antibody mAb114. […] Inmazeb is a combination of three antibodies: REGN3470 (atoltivimab), REGN3479 (maftivimab), and REGN3471 (odesivimab) at a ratio of 1:1:1. […] Ebola virus, one of the members of the filovirus group, with a fatality rate of up to 90%, is possibly one of the deadliest viruses in human history. […] The next step in the development of immunotherapy for EVD was the creation of monoclonal antibodies. […] Given these limitations, can the situation be improved with existing capabilities? One approach could be the use of new antibody cocktails that interact with the maximum number of vulnerable regions in the virus, complementing each other without competition.

• #2 Ebola Virus Infection Treatment & Management: Approach Considerations, Supportive Care, Pharmacologic Therapy

  https://emedicine.medscape.com/article/216288-treatment

  Supportive therapy with attention to intravascular volume, electrolytes, nutrition, and comfort care is of benefit to the patient. […] Nucleoside analogue inhibitors of the cell-encoded enzyme S-adenosylhomocysteine hydrolase (SAH) have been shown to inhibit Zaire ebolavirus replication in adult BALB/c mice infected with mouse-adapted Ebola virus. […] Smith and colleagues found that in rhesus macaques infected with a lethal dose of Ebola virus, treatment with interferon beta early after exposure led to a significant increase in survival time, though it did not reduce mortality significantly. […] Passive immunity has been attempted by using equine-derived hyperimmune globulins and human-derived convalescent immune globulin preparations. […] Four laboratory workers in Russia who had possible Ebola exposure were treated with a combination of a goat-derived anti-Ebola immunoglobulin plus recombinant human interferon alfa-2.

• #2 Ebola disease – Management Approach | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1210/management-approach

  Ebola disease is a notifiable disease. The mainstay of treatment is early recognition of infection coupled with effective isolation and optimized supportive care in a hospital setting. […] High case fatality rates may be related to the supportive care available in resource-poor, rural settings where outbreaks have occurred, and reflect the difficulties patients in these settings have in accessing basic medical care in a healthcare structure that is overwhelmed. […] Cases imported to developed countries present a different scenario with comprehensive supportive care available in these settings, including organ support in intensive care units. Despite this, the lack of specific, proven therapies means that fatalities occur even in developed countries where best supportive care is available.

• #2

  https://link.springer.com/article/10.1007/s00134-020-05949-z

  Supportive care remains the cornerstone of patient treatment. […] A number of direct acting anti-Ebola agents were proposed and evaluated during the West African Ebola outbreak. […] Health authorities and the WHO RD blueprint under the ethical framework of monitored emergency use of unregistered and investigational interventions (MEURI) recommended expanded access to investigational therapies, including three monoclonal antibodies (MAb114, ZMapp, and REGN-EB3) and one antiviral agent (remdesivir) in the 2018-2019 DRC Ebola outbreak. […] Management of patients with Ebola has evolved substantially over the past decade, from a clinical perspective of isolation and provision of oral rehydration therapy to one of treating the syndromic illness, specific patterns of organ dysfunction with oral and intravenous volume repletion, management of life-threatening electrolyte disturbances, support of renal dysfunction with dialysis, cardiovascular dysfunction with intravenous vasoactive medications, and oxygen and mechanical ventilation for respiratory failure.

• #2

  https://link.springer.com/article/10.1007/s40121-023-00913-y

  Therefore, there exists a need to improve EVD outcomes by improving the arsenal of treatments against EBOV. […] This review highlights many different mechanisms of action that are being investigated to halt viral infection, with potential molecules acting on the virus, as direct-acting antivirals, or acting on the host, as host-directed antivirals. […] Repurposing already approved drugs for non-EVD indications to treat EVD is also a promising strategy to bypass some of the disadvantages associated with conventional drug discovery.

• #2

  https://www.who.int/news/item/19-08-2022-who-makes-new-recommendations-for-ebola-treatments—–calls-for-improved-access

  Advances in supportive care and therapeutics over the past decade have revolutionized the treatment of Ebola. […] Provision of best supportive medical care to patients, combined with monoclonal antibody treatment MAb114 or REGN-EB3 now leads to recovery for the vast majority of people. […] Although WHO was able to make strong recommendations for the use of two therapeutics, there is a need for further research and evaluation of clinical interventions, as many uncertainties remain.

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