Intensive care support and clinical outcomes of patients with Ebola virus disease (EVD) in West Africa

Langer, Martin; Portella, Gina; Finazzi, Stefano; Chatenoud, Liliane; Lanini, Simone; Vairo, Francesco; Fowler, Robert; Miccio, Rossella; Ippolito, Giuseppe; Bertolini, Guido; Strada, Gino

doi:10.1007/s00134-018-5308-4

Cited by 21 publications

(16 citation statements)

References 32 publications

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“…The observations of temporary fluid and vasoactive medication responsiveness may shed light on a recent report that demonstrated that while generally ineffective during the West African outbreak, a subset of patients, with a moderate viral load, benefited from ICU-type supportive care [27]. We hypothesize that responsiveness to supportive care may enable patients with moderate disease to survive long enough for immune responses to control the infection.…”

Section: Discussionmentioning

confidence: 81%

Impact of intensive care unit supportive care on the physiology of Ebola virus disease in a universally lethal non-human primate model

Poliquin¹,

Funk²,

Jones³

et al. 2019

ICMx

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Background There are currently limited data for the use of specific antiviral therapies for the treatment of Ebola virus disease (EVD). While there is anecdotal evidence that supportive care may be effective, there is a paucity of direct experimental data to demonstrate a role for supportive care in EVD. We studied the impact of ICU-level supportive care interventions including fluid resuscitation, vasoactive medications, blood transfusion, hydrocortisone, and ventilator support on the pathophysiology of EVD in rhesus macaques infected with a universally lethal dose of Ebola virus strain Makona C07. Methods Four NHPs were infected with a universally lethal dose Ebola virus strain Makona, in accordance with the gold standard lethal Ebola NHP challenge model. Following infection, the following therapeutic interventions were employed: continuous bedside supportive care, ventilator support, judicious fluid resuscitation, vasoactive medications, blood transfusion, and hydrocortisone as needed to treat cardiovascular compromise. A range of physiological parameters were continuously monitored to gage any response to the interventions. Results All four NHPs developed EVD and demonstrated a similar clinical course. All animals reached a terminal endpoint, which occurred at an average time of 166.5 ± 14.8 h post-infection. Fluid administration may have temporarily blunted a rise in lactate, but the effect was short lived. Vasoactive medications resulted in short-lived improvements in mean arterial pressure. Blood transfusion and hydrocortisone did not appear to have a significant positive impact on the course of the disease. Conclusions The model employed for this study is reflective of an intramuscular infection in humans (e.g., needle stick) and is highly lethal to NHPs. Using this model, we found that the animals developed progressive severe organ dysfunction and profound shock preceding death. While the overall impact of supportive care on the observed pathophysiology was limited, we did observe some time-dependent positive responses. Since this model is highly lethal, it does not reflect the full spectrum of human EVD. Our findings support the need for continued development of animal models that replicate the spectrum of human disease as well as ongoing development of anti-Ebola therapies to complement supportive care.

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Section: Discussionmentioning

confidence: 81%

Impact of intensive care unit supportive care on the physiology of Ebola virus disease in a universally lethal non-human primate model

Poliquin¹,

Funk²,

Jones³

et al. 2019

ICMx

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“…However, given the resource constraints typical of most outbreak areas, the capacity to deliver critical care is limited by gaps at the personnel, equipment and facility levels. The knowledge of modern critical care of patients with EVD stems from the care of several patients who acquired EBOV infection in Western Africa but were managed in the USA and Europe 140,175,[199][200][201][202] , and limited experience in an ETU in Sierra Leone that was equipped with intensive care unit (ICU) capabilities 203 . Substantial pre-planning was necessary to provide treatment for critically ill patients, to ensure the availability of physicians with experience in airway management and dialysis, for example, and the necessary equipment and appropriate PPE for potentially aerosol-generating procedures.…”

Section: Critical Carementioning

confidence: 99%

Ebola virus disease

Jacob

Crozier

Fischer

et al. 2020

Nat Rev Dis Primers

456

345

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To date, 12 distinct filoviruses have been described 1. The seven filoviruses that have been found in humans belong either to the genus Ebolavirus (Bundibugyo virus (BDBV), Ebola virus (EBOV), Reston virus (RESTV), Sudan virus (SUDV) and Taï Forest virus (TAFV); Fig. 1) or to the genus Marburgvirus (Marburg virus (MARV) and Ravn virus (RAVV)) 2. The WHO International Classification of Diseases Revision 11 (ICD-11) of 2018 recognizes two major subcategories of filovirus disease (FVD): Ebola disease caused by BDBV, EBOV, SUDV or TAFV, and Marburg disease caused by MARV or RAVV. Ebola virus disease (EVD) is defined as a disease only caused by EBOV. This subcategorization of FVD is largely based on the increasing evidence of molecular differences between ebolaviruses and marburgviruses, differences that may influence virus-host reservoir tropism, pathogenesis and disease phenotype in accidental primate hosts 2. Since the discovery of filoviruses in 1967 (reF. 3), 43 FVD outbreaks (excluding at least five laboratoryacquired infections) have been recorded in or exported from Africa 4. The epidemiological definition of outbreak is one or more cases above the known endemic prevalence. For example, the single case of TAFV infection recorded in a setting in which FVD had never been reported before (Côte d'Ivoire) 5 is still considered an outbreak. All FVD outbreaks, with the exception of that caused by TAFV, were characterized by extremely high case-fatality rates (CFRs, also known as lethality). Until 2013, the most extensive outbreak, caused by SUDV, involved 425 cases and 224 deaths (CFR 52.7%) 6. The overall limited numbers of FVD cases (1967-2013: 2,886 cases including 1,982 deaths 4), the typical remote and rural locations of outbreaks and the often delayed announcement of new outbreaks to the international community 7 have prevented the systematic study of clinical FVD in humans. Thus, the commonly used description of FVD was derived either from observation of small groups of patients in care settings that were not well-equipped for diagnosis, treatment and disease characterization, or from observations of even smaller samples, such as individuals who were transferred from Equatorial Africa to Europe and the USA or who fell sick in Europe or the USA after contracting the virus elsewhere. Pathological characterization of FVD via autopsies has been rare 7,8. In the absence of extensive human clinical data, FVD could only be defined further via the use of experimental animal infections 9,10 .

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“…hospitals in high-income countries 2,[61][62] or settings in low and middle-income countries where high standard of care can be guaranteed). 63 At best this aRCT would be a part of an ongoing integrated intervention for infection control that also includes hospital-based surveillance of MDR bacteria and antimicrobial stewardship programmes. 64 The aRCT is expected to enroll complex patients potentially in need of multiple simultaneous empiric therapies.…”

Section: Ceftazidime/avibactam: An Overview Of Current Knowledge Frommentioning

confidence: 99%

Non-inferiority versus superiority trial design for new antibiotics in an era of high antimicrobial resistance: the case for post-marketing, adaptive randomised controlled trials

Lanini

Ioannidis

Vairo

et al. 2019

The Lancet Infectious Diseases

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Antimicrobial resistance (AMR) is one of the most important threats to global health security. A range of Gram-negative bacteria (GNB) associated with high morbidity and mortality rates are now resistant to virtually all available antibiotics. In this context of urgency to develop novel drugs, new antibiotics for multi drug resistant (MDR) GNB (namely, ceftazidime-avibactam, plazomicin and meropenem-varbobactam) have been approved by regulatory authorities on grounds of non-inferiority trials which provided no direct evidence of their efficacy against MDR such as Enterobacteriaceae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia cepacia and Acinetobacter baumannii. The use of noninferiority and superiority trials and selection of appropriate and optimal study designs remains a major challenge in the development, registration, and post-marketing implementation of new antibiotics. Using as an example, the development process of ceftazidime-avibactam, we propose a strategy for a new research framework based on adaptive randomized clinical trials (aRCTs). The operational research strategy has the aim of assessing the efficacy of new antibiotics in special groups of patients, such as those infected with MDR bacteria, who were not included in earlier phase studies, and for whom it is important to establish an appropriate standard of care. 82. Highlights of prescribing information Vabomere™ (meropenem and vaborbactam) Food and Drug

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Intensive care support and clinical outcomes of patients with Ebola virus disease (EVD) in West Africa

Cited by 21 publications

References 32 publications

Impact of intensive care unit supportive care on the physiology of Ebola virus disease in a universally lethal non-human primate model

Impact of intensive care unit supportive care on the physiology of Ebola virus disease in a universally lethal non-human primate model

Ebola virus disease

Non-inferiority versus superiority trial design for new antibiotics in an era of high antimicrobial resistance: the case for post-marketing, adaptive randomised controlled trials

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