Outcomes of Collaborative US-European Treatment of Ebola Cases Reported

MedicalResearch.com Interview with:

Tim Uyeki MD, MPH, MPP Influenza Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention and Associate Clinical Professor of Pediatrics Department of Pediatrics San Francisco General Hospital

Dr. Tim Uyeki

Tim Uyeki MD, MPH, MPP
Influenza Division
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention and
Associate Clinical Professor of Pediatrics
Department of Pediatrics
San Francisco General Hospital

Medical Research: What is the background for this study?

Dr. Uyeki: During 2014-2015, 27 patients with Ebola virus disease (EVD) were hospitalized in the United States and Europe. Frequent international teleconferences were convened among U.S. and European clinicians caring for EVD patients, often on a weekly basis, to share detailed information and suggestions on clinical management of these patients. We collected clinical, epidemiologic, laboratory, and virologic data on all of these patients and performed descriptive data analyses. We summarized our findings in this article.

Medical Research: What are the main findings?

Dr. Uyeki: Of the 27 patients with Ebola virus disease cared for in 15 hospitals in nine countries, the median age was 36 years; 19 (70%) were male; 9 of 26 (35%) had underlying medical conditions; and 22 (81%) were healthcare personnel, including 17 of 22 (77%) who had worked in an Ebola treatment unit in West Africa. Of the 27 patients, 20 (74%) were medically evacuated from West Africa, 4 (15%) were imported cases, and 3 (11%) were healthcare personnel who acquired Ebola virus infection while caring for EVD patients in the U.S. or Europe. At illness onset, the signs and symptoms of EVD were non-specific; the most common symptom reported was fatigue. At admission to a hospital in the U.S. or Europe, most patients had fever, weakness, and gastrointestinal symptoms. The median time from illness onset to hospitalization was four days.

During hospitalization, all patients had diarrhea, often profuse watery diarrhea; and most experienced electrolyte abnormalities such as hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia, as well as hypoalbuminemia. One third of patients experienced renal abnormalities such as oliguria or anuria, nearly 60% were clinically diagnosed with systemic inflammatory response syndrome, and one third were clinically diagnosed with encephalopathy or encephalitis. Although minor bleeding abnormalities were reported in some patients, only two patients had any gross hemorrhage. Leukopenia was observed during the first week of illness, with increases in white blood cell count during the second week. Thrombocytopenia was common, and aminotransferase levels peaked in the second week of illness. Creatine kinase and lactate levels were elevated in most of the patients who were tested. Ebola virus levels in blood peaked on the seventh day of illness, and critical illness occurred at the end of the first week and during the second week after illness onset. All patients received intravenous fluids; most were treated empirically with antibiotics; and 85% received an investigational therapy, including 70% who received at least two experimental therapies. Eleven (41%) patients were critically ill, including seven who required invasive mechanical ventilation and five who received continuous renal replacement therapy. Five (18.5%) patients died (81.5% survival).

Medical Research: What should clinicians and patients take away from your report?

Dr. Uyeki: Patients with Ebola virus disease may present initially with mild, non-specific signs and symptoms and can deteriorate rapidly once profuse diarrhea begins. Early initiation of supportive care may be beneficial. Close monitoring and aggressive supportive care is needed, including intravenous fluid resuscitation and hydration and correction of electrolyte abnormalities. Critical care management and advanced organ support (invasive mechanical ventilation and continuous renal replacement therapy) is needed for critically ill patients who experience respiratory failure, septic shock, and renal failure. While mortality from EVD is high, some critically ill patients with both respiratory and renal failure can survive with excellent critical care nursing, clinical management, and advanced organ support.

To protect themselves and others, healthcare personnel caring for patients with EVD must implement and follow recommended infection prevention and control measures, including strict adherence to proper donning, doffing, and use of recommended personal protective equipment.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Uyeki: Clinical research is needed to optimize clinical management of  Ebola virus disease patients and to determine the effectiveness of interventions in low-resource and higher-resource settings. This includes retrospective and prospective observational studies of clinical management and randomized controlled trials (RCTs) of interventions. Standardized clinical data collection protocols must be approved in advance and be available to collect clinical data on EVD patients. Examples of possible interventions that could be studied include the benefit of early oral versus intravenous fluid hydration and the benefit of early anti-motility treatment once EVD-associated diarrhea has started. These studies would be helped by the availability of accurate, highly sensitive and specific rapid diagnostic tests currently in development for detection of Ebola virus in clinical specimens. It is not possible to assess the benefits or harms of the investigational therapies that were given to most EVD patients in the U.S. and Europe because the administration of the therapies was uncontrolled. RCTs, such as the trial conducted for ZMapp, are needed to determine the efficacy of investigational treatments for EVD patients. RCT protocols for investigational therapies need to be approved in advance of the next EVD outbreak and available therapeutic products need to be pre-positioned for rapid access at clinical sites. 

Medical Research: Is there anything else you would like to add?

Dr. Uyeki: This effort was the result of a wonderful international collaboration of clinicians in the U.S. and eight European countries who freely shared detailed information, experiences, and suggestions for clinical management of EVD patients on many teleconferences. The goal was to help each other as knowledge evolved on clinical management of patients with Ebola virus disease. As a result of the teleconferences, an international clinical network was formed and standardized clinical data collection was implemented that resulted in this article. It is important to note that patients who survived EVD in the U.S., Europe, and especially those many thousands of patients who have survived in West Africa, may experience challenges in fully recovering their normal health. A wide range of symptoms and complications of variable severity have been reported in EVD survivors, and the need for medical care in many survivors is ongoing.

Citation:

Clinical Management of Ebola Virus Disease in the United States and Europe

Timothy M. Uyeki, M.D., M.P.H., M.P.P., Aneesh K. Mehta, M.D., Richard T. Davey, Jr., M.D., Allison M. Liddell, M.D., Timo Wolf, M.D., Pauline Vetter, M.D., D.T.M.&H., Stefan Schmiedel, M.D., Thomas Grünewald, M.D., Ph.D., Michael Jacobs, M.B., B.S., Ph.D., D.T.M.&H., Jose R. Arribas, M.D., Laura Evans, M.D., Angela L. Hewlett, M.D., Arne B. Brantsaeter, M.D., Ph.D., M.P.H., Giuseppe Ippolito, M.D., Christophe Rapp, M.D., Ph.D., Andy I.M. Hoepelman, M.D., Ph.D., and Julie Gutman, M.D. for the Working Group of the U.S.–European Clinical Network on Clinical Management of Ebola Virus Disease Patients in the U.S. and Europe

N Engl J Med 2016; 374:636-646
February 18, 2016 DOI: 10.1056/NEJMoa1504874

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Dr. Tim Uyek (2016). Outcomes of Collaborative US-European Treatment of Ebola Cases Reported MedicalResearch.com

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