Ebola virus disease treatment research

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This article is about current experimental treatments to fight the Ebola virus. For vaccine information, see Ebola vaccine.

Researcher working with the Ebola virus while wearing a BSL-4 positive pressure suit

Ebola virus disease (research) or simply Ebola, is a disease that affects humans and other primates caused by ebolaviruses; there is no cure or specific treatment that is currently approved,[1] treatment is primarily supportive in nature.[2]

Contents

  • 1 Overview
  • 2 Experimental treatments being researched
    • 2.1 Antibodies
    • 2.2 Antivirals and other drugs
  • 3 Blood products
  • 4 Existing drugs without anti-Ebola activity
  • 5 Potential diagnostic tests
  • 6 Hemopurifier
  • 7 See also
  • 8 References
  • 9 Further reading

Overview[edit]

In March 2014, the World Health Organization (WHO) reported a major Ebola outbreak in Guinea, a western African nation.[3] The disease then rapidly spread to the neighboring countries of Liberia and Sierra Leone. The 2014 West African Ebola outbreak is the largest Ebola outbreak ever documented, and the first recorded in the region.[3]

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.[4] The unavailability of treatments in the most-affected regions has spurred controversy, with some calling for experimental drugs to be made more widely available in Africa on a humanitarian basis, and others warning that making unproven drugs widely available would be unethical, especially in light of past experimentation conducted in developing countries by Western drug companies.[5][6] As a result of the controversy, on 12 August an expert panel of the WHO endorsed the use of interventions with as-yet-unknown effects for both treatment and prevention of Ebola, and also said that deciding which treatments should be used and how to distribute them equitably were matters that needed further discussion.[7]

Conventional trials to study efficacy by exposure of humans to the pathogen are obviously not feasible in this case. For such situations, the FDA has established the “Animal Efficacy Rule” allowing limited licensure to be approved on the basis of animal model studies that replicate human disease, combined with evidence of safety. A number of experimental treatments are being considered for use in the context of this outbreak, and are currently or will soon undergo clinical trials.[8] A distributed computing project, Outsmart Ebola Together, has been launched by World Community Grid in collaboration with the Scripps Research Institute to help find chemical compounds to fight the disease. It uses the idle processing capacity of volunteers’ computers and tablets.[9]

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

Experimental treatments being researched[edit]

Antibodies[edit]

  • ZMapp is a combination of three chimeric antibodies effective in Ebola-infected monkeys.[11] The limited supply of the antibody preparation was used to treat a small number of individuals infected with the Ebola virus early in the 2014-5 West Africa outbreak; although some individuals recovered, the outcome is not considered statistically significant.[12][13] A Phase 1/2 trial started in Liberia and the United States on 27 February 2015.[14][15]
  • Monoclonal antibodies derived from blood samples of infected patients, under development by Theraclone Sciences in Seattle.[16]
  • MIL 77 is an experimental drug used for the first time in a medical evacuated case in the United Kingdom, who survived the virus after receiving this drug. The doctors who used this treatment did confirm it is too early to speculate if this drug was instrumental in her recovery.[17] The drug was tested in 18 monkeys infected with the deadly virus, and all the primates survived according to the researchers. MIL 77 closely resembles ZMapp.[18]
  • The mAb114 monoclonal antibody has been developed by Jean-Jacques Muyembe at the National Institute for Biomedical Research in the Democratic Republic of the Congo (DRC), and is derived from an EVD survivor of the 1995 DRC outbreak in Kikwit who still had circulating anti-Ebola antibodies 11 years later; it has been tested in macaques but not in humans.[19][20][21]

Antivirals and other drugs[edit]

  • Favipiravir (Avigan) is a broad-spectrum antiviral drug, which appears to be useful in a mouse model of Ebola disease.[22][23] A Phase 2 clinical trial started in Guinea during December 2014,[24][25] with early reports indicating that it has some benefit.[26]
  • BCX4430 is a broad-spectrum nucleoside analog antiviral drug developed by BioCryst Pharmaceuticals.[27] A Phase 1 trial started in December 2014.[28][29] The drug was effective in Ebola-infected monkeys.[30]
  • Brincidofovir, an antiviral drug, has been granted an emergency FDA approval as an investigational new drug for the treatment of Ebola after it was found to be effective against Ebola virus in in vitro tests.[31] A Phase 2 trial started during January 2015 in Liberia, but was subsequently discontinued due to a lack of suitable subjects.[32][33][34]
  • TKM-Ebola is an RNA interference drug candidate; a Phase II trial started on 11 March 2015 and stopped enrolling new subjects on 19 June 2015 after it appeared not to work; statistical analysis was ongoing at the time.[35][36]
  • AVI-7537 is an antiviral drug developed by Sarepta Therapeutics, which was effective in Ebola-infected monkeys.[37][38] A Phase 1 trial May 2010 to November 2011 showed that the drug was safe in healthy adults;[39][40] however, a later Phase 1 trial was withdrawn due to funding constraints.[41]
  • JK-05 is an antiviral drug developed by Sihuan Pharmaceutical along with Academy of Military Medical Sciences. In tests on mice, JK-05 shows efficacy against a range of viruses, including Ebola. It is claimed to have a simple molecular structure, which should be readily amenable to synthesis scale-up for mass production. The drug has been given preliminary approval by the Chinese authorities to be available for Chinese health workers involved in combating the outbreak, and Sihuan are preparing to conduct clinical trials in West Africa.[42][43]

Blood products[edit]

The 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.[44] A study in Sierra Leone started in November 2014, and preliminary results show an 80 percent survival rate.[45] Trials in Liberia and Guinea started in January 2015, with funding from the Gates Foundation.[46] Blood transfusions were also used in a 1995 outbreak in the Democratic Republic of the Congo, and 7 out of 8 patients survived.[47]

Existing drugs without anti-Ebola activity[edit]

Ribavirin is also known to be ineffective against ebolaviruses despite its effectiveness against other viral hemorrhagic fevers such as Lassa fever.[48] Interferon therapies have been tried as a form of treatment for EVD, but were found to be ineffective.[49]

Potential diagnostic tests[edit]

One issue which hinders control of Ebola is that diagnostic tests which are currently available require specialised equipment and highly trained personnel. Since there are few suitable testing centres in West Africa, this leads to delay in diagnosis. In December, a conference in Geneva will aim to work out which diagnostic tools could identify Ebola reliably and more quickly. The meeting, convened by the WHO and the non-profit Foundation for Innovative New Diagnostics, seeks to identify tests that can be used by untrained staff, do not require electricity or can run on batteries or solar power and use reagents that can withstand temperatures of 40 °C.[50]

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

  • Diagnostics-in-a-Suitcase, based on recombinase polymerase amplification (RPA). The new equipment, about the size of a laptop and solar-powered, allows testing to be done in remote areas; testing commenced in Guinea during January 2015.[51]
  • In December 2014, the FDA approved LightMix (R) Ebola Zaire rRT-PCR Test for emergency use on patients with symptoms of Ebola.[52]
  • Massachusetts Institute of Technology has developed a 10-minute Ebola test using Matrix Multiplexed Diagnostic (MMDx) technology. This still has to complete testing to gain FDA approval.[53]
  • Corgenix Medical Corp announced on 26 February that health regulators had approved its rapid Ebola test for emergency use. The ReEBOV Antigen Rapid Test involves putting a drop of blood on a paper strip and waiting for at least 15 minutes for a reaction.[54]
  • On 29 March, a new rapid Ebola virus diagnostic kit/test was developed by British military scientists and NHS in Sierra Leone.[55]

Hemopurifier[edit]

The Hemopurifier is a single-use disposable cartridge designed for use with dialysis machines and other blood circulatory pumps. It functions to selectively remove harmful substances from the blood, giving a potential method of addressing diseases.[citation needed] During October 2014 the Hemopurifier was used as an adjunct in the treatment of a patient who was suffering from Ebola, who subsequently recovered.[56] The FDA has subsequently approved the device for testing in up to 20 infected Ebola cases in the United States.[57]

See also[edit]

  • Ebola vaccine
  • Ebola virus epidemic in West Africa

References[edit]

  • ^ Choi JH, Croyle MA; Croyle (December 2013). “Emerging targets and novel approaches to Ebola virus prophylaxis and treatment”. BioDrugs. 27 (6): 565–83. doi:10.1007/s40259-013-0046-1. PMC 3833964 . PMID 23813435. 
  • ^ Clark DV, Jahrling PB, Lawler JV; Jahrling; Lawler (September 2012). “Clinical management of filovirus-infected patients”. Viruses. 4 (9): 1668–86. doi:10.3390/v4091668. PMC 3499825 . PMID 23170178. CS1 maint: Multiple names: authors list (link)
  • ^ a b “Guidelines for Evaluation of US Patients Suspected of Having Ebola Virus Disease”. CDC. 1 August 2014. Retrieved 5 August 2014. 
  • ^ Roberts, Dan. News World news “Ebola CDC director warns Ebola like ‘forest fire’ as Congress readies for hearing” – Ebola crisis live updates – The Guardian. Retrieved 16 October 2014.
  • ^ “Three leading Ebola experts call for release of experimental drug”. Los Angeles Times. 6 August 2014. 
  • ^ “In Ebola Outbreak, Who Should Get Experimental Drug?”. The New York Times. 8 August 2014. 
  • ^ “Ethical considerations for use of unregistered interventions for Ebola viral disease (EVD)”. World Health Organization. 12 August 2014. 
  • ^ Briggs, Helen (7 August 2014) “Ebola: Experimental drugs and vaccines”, BBC News, Health, Retrieved 8 August 2014
  • ^ Park, Alice (19 December 2014). “How Your Tablet Can Help Find an Ebola Cure”. Retrieved 19 December 2014. 
  • ^ “Ebola 2.0 – Lessons Learned in 2014 May Not Suffice”. Africa Times. 2017-05-22. Retrieved 2017-05-25. 
  • ^ Nathan Seppa (29 August 2014). “ZMapp drug fully protects monkeys against Ebola virus”. Science News. Society for Science & the Public. Retrieved 1 October 2014. 
  • ^ Tosh PK, Sampathkumar P; Sampathkumar (December 2014). “What Clinicians Should Know About the 2014 Ebola Outbreak”. Mayo Clin Proc. 89 (12): 1710–17. doi:10.1016/j.mayocp.2014.10.010. PMID 25467644. 
  • ^ Kroll, David (26 August 2014). “How will we know if the Ebola drugs worked?”. Forbes. Retrieved 1 October 2014. 
  • ^ “Liberia-U.S. clinical research partnership opens trial to test Ebola treatments”. National Institutes of Health (NIH). Retrieved 27 February 2015. 
  • ^ “Putative Investigational Therapeutics in the Treatment of Patients With Known Ebola Infection”. ClinicalTrials.gov. U.S. National Institutes of Health. Retrieved 1 August 2015. 
  • ^ “Theraclone Sciences’ I-STAR™ Technology Chosen by Wellcome Trust to Identify Therapeutic Antibodies Against Ebola Virus” (PDF). Theraclone Sciences. Retrieved 1 August 2015. 
  • ^ “British medic declared free of Ebola”. BBC News. 27 March 2015. Retrieved 27 March 2015. 
  • ^ “hIs MIL-77 The New Ebola-Fighting Wonder Drug?”. Sky News. 27 March 2015. Retrieved 27 March 2015. 
  • ^ “ProMED-mail post”. www.promedmail.org. Retrieved 25 May 2018. 
  • ^ Erika Check Hayden (25 February 2016). “Ebola survivor’s blood holds promise of new treatment”. Nature. doi:10.1038/nature.2016.19440. 
  • ^ Davide Corti et al. (2016). “Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody”. Science. 351: 1339–42. doi:10.1126/science.aad5224. CS1 maint: Uses authors parameter (link) CS1 maint: Explicit use of et al. (link)
  • ^ Gatherer D (2014). “The 2014 Ebola virus disease outbreak in West Africa”. J. Gen. Virol. 95 (Pt 8): 1619–24. doi:10.1099/vir.0.067199-0. PMID 24795448. 
  • ^ Oestereich, L.; Lüdtke, A.; Wurr, S.; Rieger, T.; Muñoz-Fontela, C.; Günther, S. “Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model”. Antiviral Research. 105: 17–21 year = 2014. doi:10.1016/j.antiviral.2014.02.014. PMID 24583123. CS1 maint: Missing pipe (link)
  • ^ “Guinea: Clinical Trial for Potential Ebola Treatment Started in MSF Clinic in Guinea”. AllAfrica – All the Time. Retrieved 28 December 2014. 
  • ^ “Efficacy of Favipiravir Against Ebola (JIKI)”. ClinicalTrials.gov. U.S. National Institutes of Health. Retrieved 1 August 2015. 
  • ^ “Fujifilm’s Toyama unit set to publish promising early clinical results in treating Ebola”. Retrieved 7 February 2015. 
  • ^ David Kroll (29 August 2014). “BioCryst to Launch NHP Ebola Drug Safety, Efficacy Studies ‘Within Weeks'”. Forbes. Retrieved 5 October 2014. 
  • ^ “DURHAM: BioCryst receives additional funding for Ebola drug”. WNCN. 18 September 2014. Retrieved 5 October 2014. 
  • ^ “A Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BCX4430”. ClinicalTrials.gov. U.S. National Institutes of Health. Retrieved 1 August 2015. 
  • ^ “BioCryst’s Ebola drug shows promise in animal study”. Reuters. Retrieved 27 December 2014. 
  • ^ Staff (3 September 2014). “Chimerix experimental drug shows promise in fighting Ebola virus”. WNCN. Retrieved 7 October 2014. 
  • ^ “Trials of untested Ebola drugs begin in West Africa”. Reuters. Retrieved 6 January 2015. 
  • ^ “Chimerix’s Brincidofovir Selected for Use in Ebola Clinical Trial in West Africa by International Consortium”. Chimerix, Inc. Retrieved 1 August 2015. 
  • ^ “Chimerix Ends Brincidofovir Ebola Trials To Focus On Adenovirus And CMV”. Forbes. Retrieved 31 January 2015. 
  • ^ Kupferschmidt, Kai (11 March 2015). “New Ebola drug trial starts in Sierra Leone”. Science Magazine. AAAS. Retrieved 1 August 2015. 
  • ^ Vogel, Gretchen; Kupferschmidt, Kai (19 June 2015). “In setback for potential Ebola drug, company halts trial”. news.sciencemag.org. Retrieved 24 June 2015. 
  • ^ Blum, Karen. “Drug Targeting Ebola Virus Protein VP24 Shows Promise in Monkeys”. mBiosphere. American Society for Microbiology. Retrieved 1 August 2015. 
  • ^ “AVI 6002 (AVI-7537) Drug Therapy (Sarepta Therapeutics) for Treating Ebola Virus Disease”. ECRI Institute. Retrieved 1 August 2015. 
  • ^ Heald, A. E.; Iversen, P. L.; Saoud, J. B.; Sazani, P.; Charleston, J. S.; Axtelle, T.; Wong, M.; Smith, W. B.; Vutikullird, A.; Kaye, E. (25 August 2014). “Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single-Ascending-Dose Studies”. Antimicrobial Agents and Chemotherapy. 58 (11): 6639–47. doi:10.1128/AAC.03442-14. PMC 4249403 . PMID 25155593. 
  • ^ “Safety Study of Single Administration Post-Exposure Prophylaxis Treatment for Ebola Virus”. ClinicalTrials.gov. U.S. National Institutes of Health. Retrieved 1 August 2015. 
  • ^ “A Study to Assess the Safety, Tolerability and Pharmacokinetics of AVI-7537 in Healthy Adult Volunteers”. ClinicalTrials.gov. U.S. National Institutes of Health. Retrieved 1 August 2015. 
  • ^ “China approves Ebola drug for emergency use. Kristine Yang, Bioworld.com”. BioWorld. 
  • ^ “China sends Ebola drug to Africa, eyes clinical trials”. Reuters. Retrieved 31 October 2014. 
  • ^ “Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease Empirical treatment during outbreaks”. WHO. Retrieved 4 October 2014. 
  • ^ Maxmen, Amy (16 February 2015). “Blood transfusions show early promise as possible Ebola cure”. Al Jazeera America. Retrieved 1 August 2015. 
  • ^ Butler, Declan (15 December 2014). “First trials of blood-based Ebola therapy kick off”. Nature News. Retrieved 1 August 2015. 
  • ^ Mupapa, K.; Massamba, M.; Kibadi, K.; Kuvula, K.; Bwaka, A.; Kipasa, M.; Colebunders, R.; Muyembe‐Tamfum, J. J. (February 1999). “Treatment of Ebola Hemorrhagic Fever with Blood Transfusions from Convalescent Patients”. The Journal of Infectious Diseases. 179 (s1): S18–S23. doi:10.1086/514298. PMID 9988160. 
  • ^ Goeijenbier M, van Kampen JJ, Reusken CB, Koopmans MP, van Gorp EC (November 2014). “Ebola virus disease: a review on epidemiology, symptoms, treatment and pathogenesis”. Neth J Med. 72 (9): 442–48. PMID 25387613. 
  • ^ Chippaux JP (October 2014). “Outbreaks of Ebola virus disease in Africa: the beginnings of a tragic saga”. J Venom Anim Toxins Incl Trop Dis. 20 (1): 44. doi:10.1186/1678-9199-20-44. PMC 4197285 . PMID 25320574. 
  • ^ “Ebola Experts Seek to Expand Testing”. Scientific American. Retrieved 11 December 2014. 
  • ^ Paddock PhD, Catharine (9 January 2015). “‘Lab in a suitcase’ set to improve Ebola virus control”. Medical News Today. Retrieved 11 April 2015. 
  • ^ Marta Falconi (29 December 2014). “Roche Secures Emergency Approval by U.S. Regulators for Ebola Test”. WSJ. Retrieved 29 December 2014. 
  • ^ “MIT designs 10-minute ebola test”. gizmag.com. Retrieved 26 February 2015. 
  • ^ “FDA approves Corgenix’s Ebola test for emergency use”. Reuters. Retrieved 27 February 2015. 
  • ^ Lisa O’Carroll. “Ebola rapid diagnostic kit developed by UK scientists in Sierra Leone”. the Guardian. Retrieved 10 April 2015. 
  • ^ “New Ebola Treatment Filters Virus Out of the Blood”. Time. Retrieved 3 January 2015. 
  • ^ “FDA allows testing of Aethlon device in Ebola patients”. Reuters. 2 January 2015. Retrieved 2 January 2015. 
  • Further reading[edit]

    • “Ebola virus disease Information for Clinicians in U.S. Healthcare Settings | Ebola Hemorrhagic Fever | CDC”. www.cdc.gov. Centers for Disease Control and Prevention. Retrieved 19 July 2016. 
    • Nelson, Elizabeth A.; Barnes, Alyson B.; Wiehle, Ronald D.; Fontenot, Gregory K.; Hoenen, Thomas; White, Judith M. (2 August 2016). “Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications”. Viruses. 8 (8): 206. doi:10.3390/v8080206. Retrieved 14 August 2016. 
    • Morais, Victor (26 August 2016). “An Old Solution for a New Problem: Antiserum against Emerging Infectious Diseases”. Frontiers in Public Health. 4. doi:10.3389/fpubh.2016.00178. ISSN 2296-2565. PMC 5000394 . PMID 27617259. 
    • “Ebola/Marburg Research”. www.niaid.nih.gov. NIH: National Institute of Allergy and Infectious Diseases. Retrieved 29 August 2016. 
    • “Medscape: Ebola Virus RNA Evident in Semen for a year or longer”. www.medscape.com. Medscape. Retrieved 1 September 2016. 
    • Leligdowicz, Aleksandra; Fischer, William A.; Uyeki, Timothy M.; Fletcher, Thomas E.; Adhikari, Neill K. J.; Portella, Gina; Lamontagne, Francois; Clement, Christophe; Jacob, Shevin T.; Rubinson, Lewis; Vanderschuren, Abel; Hajek, Jan; Murthy, Srinivas; Ferri, Mauricio; Crozier, Ian; Ibrahima, Elhadj; Lamah, Marie-Claire; Schieffelin, John S.; Brett-Major, David; Bausch, Daniel G.; Shindo, Nikki; Chan, Adrienne K.; O’Dempsey, Tim; Mishra, Sharmistha; Jacobs, Michael; Dickson, Stuart; Lyon, G. Marshall; Fowler, Robert A. (1 January 2016). “Ebola virus disease and critical illness”. Critical Care. 20: 217. doi:10.1186/s13054-016-1325-2. ISSN 1364-8535. Retrieved 3 September 2016. 
    • Group, The PREVAIL II Writing (13 October 2016). “A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection”. New England Journal of Medicine. 375 (15): 1448–1456. doi:10.1056/NEJMoa1604330. ISSN 0028-4793. PMC 5086427 . PMID 27732819. Retrieved 14 October 2016. 
    • González, Víctor M.; Martín, M. Elena; Fernández, Gerónimo; García-Sacristán, Ana (16 December 2016). “Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses”. Pharmaceuticals. 9 (4): 78. doi:10.3390/ph9040078. Retrieved 22 December 2016. 

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