Ebola Virus Disease Outcome Research Articles

Macrophage infection, activation, and histopathological findings in ebolavirus infection.

Macrophages contribute to Ebola virus disease through their susceptibility to direct infection, their multi-faceted response to ebolaviruses, and their association with pathological findings in tissues throughout the body. Viral attachment and entry factors, as well as the more recently described influence of cell polarization, shape macrophage susceptibility to direct infection. Moreover, the study of Toll-like receptor 4 and the RIG-I-like receptor pathway in the macrophage response to ebolaviruses highlight important immune signaling pathways contributing to the breadth of macrophage responses. Lastly, the deep histopathological catalogue of macrophage involvement across numerous tissues during infection has been enriched by descriptions of tissues involved in sequelae following acute infection, including: the eye, joints, and the nervous system. Building upon this knowledge base, future opportunities include characterization of macrophage phenotypes beneficial or deleterious to survival, delineation of the specific roles macrophages play in pathological lesion development in affected tissues, and the creation of macrophage-specific therapeutics enhancing the beneficial activities and reducing the deleterious contributions of macrophages to the outcome of Ebola virus disease.

Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes

We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus–infected patients. We studied the relationship between KIR–human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4–003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4–003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD.

Plasma lipidome reveals critical illness and recovery from human Ebola virus disease.

Ebola virus disease (EVD) often leads to severe and fatal outcomes in humans with early supportive care increasing the chances of survival. Profiling the human plasma lipidome provides insight into critical illness as well as diseased states, as lipids have essential roles as membrane structural components, signaling molecules, and energy sources. Here we show that the plasma lipidomes of EVD survivors and fatalities from Sierra Leone, infected during the 2014-2016 Ebola virus outbreak, were profoundly altered. Focusing on how lipids are associated in human plasma, while factoring in the state of critical illness, we found that lipidome changes were related to EVD outcome and could identify states of disease and recovery. Specific changes in the lipidome suggested contributions from extracellular vesicles, viremia, liver dysfunction, apoptosis, autophagy, and general critical illness, and we identified possible targets for therapies enhancing EVD survival.

Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea.

BACKGROUND. The pathogenesis of Ebola virus (EBOV) disease (EVD) is poorly characterized. The establishment of well-equipped diagnostic laboratories close to Ebola treatment centers (ETCs) has made it possible to obtain relevant virological and biological data during the course of EVD and to assess their association with the clinical course and different outcomes of the disease. METHODS. We were responsible for diagnosing EBOV infection in patients admitted to two ETCs in forested areas of Guinea. The pattern of clinical signs was recorded, and an etiological diagnosis was established by RT-PCR for EBOV infection or a rapid test for malaria and typhoid fever. Biochemical analyses were also performed. RESULTS. We handled samples from 168 patients between November 29, 2014, and January 31, 2015; 97 patients were found to be infected with EBOV, with Plasmodium falciparum coinfection in 18%. Overall mortality for EVD cases was 58%, rising to 86% if P. falciparum was also present. Viral load was higher in fatal cases of EVD than in survivors, and fatal cases were associated with higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT), C-reactive protein (CRP), and IL-6 levels. Furthermore, regardless of outcome, EVD was characterized by higher creatine kinase (CPK), amylase, and creatinine levels than in febrile patients without EVD, with higher blood urea nitrogen (BUN) levels in fatal cases of EVD only. CONCLUSION. These findings suggest that a high viral load at admission is a marker of poor EVD prognosis. In addition, high AST, ALT, CRP, and IL-6 levels are associated with a fatal outcome of EVD. Damage to the liver and other tissues, with massive rhabdomyolysis and, probably, acute pancreatitis, is associated with EVD and correlated with disease severity. Finally, biochemical analyses provide substantial added value at ETCs, making it possible to improve supportive rehydration and symptomatic care for patients. FUNDING. The French Ministry of Foreign Affairs, the Agence Française de Développement, and Institut Pasteur.

Ebola virus disease and pregnancy outcome: A review of the literature

Introduction: Ebola virus disease (EVD) is a disease of humans and other primates caused by Ebola viruses. The most widespread epidemic of EVD in history occurred recently in several West African countries. The burden and outcome of EVD in pregnant women remains uncertain. There are few reports to date on maternal and fetal outcomes among pregnant women with EVD, hence the justification for this comprehensive review of these published studies. Materials and Methods: Published literature in Englishthat reported on maternal and or fetal outcome among pregnant women with EVD up to May 2016 were searched in electronic databases (Google Scholar, Medline, Embase, PubMed, AJOL, and Scopus). Studies that did not meet the inclusion criteria were excluded. We extracted the following variables from each study: Geographical location, year of the study, settings of the study, participants, maternal and fetal outcome. Results: A total of 12 studies reported on 108 pregnant women and 110 fetal outcomes. Six of the studies were case reports, three retrospective studies, two cross-sectional studies, and one was a technical report. There were 91 (84.3%) deaths out of the 108 pregnant women, while only one (0.9%) fetal survival was reported out of 110. The survival rate among the 15 patients that had spontaneous abortion/stillbirth or induced delivery was 100%. Conclusion: There was a poor maternal and fetal outcome among pregnant women with EVD, and fetal evacuation significantly improves maternal survival.

Intensive Education of Health Care Workers Improves the Outcome of Ebola Virus Disease: Lessons Learned from the 2014 Outbreak in Sierra Leone.

The rare and deadly Ebola virus disease (EVD) is caused by Ebola virus (EBOV) infection. The 2014-2015 EVD outbreak in West Africa was unprecedented. Person-to-person transmission of EBOV by direct contact with the body or bodily fluids of an infected person through broken skin or unprotected mucous membrane caused rapid outbreak in communities. Nosocomial infection was the cause of death of many health care workers (HCWs). This paper aims to reveal the importance and effect of intensive education of HCWs when combating an outbreak such as EVD. We compared the curricula of two educational programs and analyzed their effects by the trend of weekly new patients. In September 2014, a three-day training program on infection, prevention and control (IPC) was organized for nurses, but it was not sufficient to achieve good outcome. In December 2014, a newly established National Ebola Training Academy was set up to offer a platform of clinical training modules for frontline Ebola response workers. This academy addressed the training needs of clinicians and hygienists who were working or will work at Ebola treatment centers that were established after the onset of the 2014 outbreak. Increased intensive contents and simulated training at the academy improved HCWs' understanding of EVD, IPC and patient care, which subsequently contributed to the survival of patients. The rapid settlement of the outbreak after introducing the Academy indicates that appropriate intensive education of HCWs is the key activity carried out to control the outbreak of EVD in Sierra Leone.

The predictor of mortality outcome in adult patients with Ebola virus disease during the 2014-2015 outbreak in Guinea.

The purpose of this study was to examine the association of any demographic and clinical factors with mortality outcome among adult patients with Ebola virus disease (EVD) in Guinea. This retrospective observational study analyzed medical records of laboratory confirmed EVD adult patients during the 2014-2015 EVD outbreak in Guinea. The associations between any demographic or clinical variables and mortality outcome of EVD were assessed using univariate and multivariate logistic regression analyses. Of 2,310 EVD adult patients included for analysis, the overall case fatality rate was 68.1%. Univariate analyses identified factors possibly associated with mortality outcome, including patient age (p < 0.001), history of visiting or close contact with a suspected or confirmed EVD patient (p = 0.035), and seven clinical symptoms on admission, i.e., fever (p = 0.003), hiccups (p < 0.001), vomiting (p = 0.003), diarrhea (p < 0.001), cough (p = 0.001), sore throat (p = 0.016), and unexplained bleeding (p = 0.021). The multivariate analysis showed that patient age was independently associated with mortality outcome of EVD (OR = 1.06; 95%CI = 1.03-1.09; p < 0.001), while none the of clinical symptoms on admission were significantly associated with the mortality outcome. Our analysis indicates that older age was the only independent factor associated with death among EVD adult patients in Guinea. This suggests that older EVD patients should receive intensive medical care and be carefully monitored.

Modelling Ebola virus dynamics: Implications for therapy

Ebola virus (EBOV) causes a severe, often fatal Ebola virus disease (EVD), for which no approved antivirals exist. Recently, some promising anti-EBOV drugs, which are experimentally potent in animal models, have been developed. However, because the quantitative dynamics of EBOV replication in humans is uncertain, it remains unclear how much antiviral suppression of viral replication affects EVD outcome in patients. Here, we developed a novel mathematical model to quantitatively analyse human viral load data obtained during the 2000/01 Uganda EBOV outbreak and evaluated the effects of different antivirals. We found that nucleoside analogue- and siRNA-based therapies are effective if a therapy with a >50% inhibition rate is initiated within a few days post-symptom-onset. In contrast, antibody-based therapy requires not only a higher inhibition rate but also an earlier administration, especially for otherwise fatal cases. Our results demonstrate that an appropriate choice of EBOV-specific drugs is required for effective EVD treatment.

Analysis of Diagnostic Findings From the European Mobile Laboratory in Guéckédou, Guinea, March 2014 Through March 2015.

Background. A unit of the European Mobile Laboratory (EMLab) consortium was deployed to the Ebola virus disease (EVD) treatment unit in Guéckédou, Guinea, from March 2014 through March 2015.Methods. The unit diagnosed EVD and malaria, using the RealStar Filovirus Screen reverse transcription–polymerase chain reaction (RT-PCR) kit and a malaria rapid diagnostic test, respectively.Results. The cleaned EMLab database comprised 4719 samples from 2741 cases of suspected EVD from Guinea. EVD was diagnosed in 1231 of 2178 hospitalized patients (57%) and in 281 of 563 who died in the community (50%). Children aged <15 years had the highest proportion of Ebola virus–malaria parasite coinfections. The case-fatality ratio was high in patients aged <5 years (80%) and those aged >74 years (90%) and low in patients aged 10–19 years (40%). On admission, RT-PCR analysis of blood specimens from patients who died in the hospital yielded a lower median cycle threshold (Ct) than analysis of blood specimens from survivors (18.1 vs 23.2). Individuals who died in the community had a median Ct of 21.5 for throat swabs. Multivariate logistic regression on 1047 data sets revealed that low Ct values, ages of <5 and ≥45 years, and, among children aged 5–14 years, malaria parasite coinfection were independent determinants of a poor EVD outcome.Conclusions. Virus load, age, and malaria parasite coinfection play a role in the outcome of EVD.

Transforming Clinical Data into Actionable Prognosis Models: Machine-Learning Framework and Field-Deployable App to Predict Outcome of Ebola Patients.

BackgroundAssessment of the response to the 2014–15 Ebola outbreak indicates the need for innovations in data collection, sharing, and use to improve case detection and treatment. Here we introduce a Machine Learning pipeline for Ebola Virus Disease (EVD) prognosis prediction, which packages the best models into a mobile app to be available in clinical care settings. The pipeline was trained on a public EVD clinical dataset, from 106 patients in Sierra Leone.Methods/Principal FindingsWe used a new tool for exploratory analysis, Mirador, to identify the most informative clinical factors that correlate with EVD outcome. The small sample size and high prevalence of missing records were significant challenges. We applied multiple imputation and bootstrap sampling to address missing data and quantify overfitting. We trained several predictors over all combinations of covariates, which resulted in an ensemble of predictors, with and without viral load information, with an area under the receiver operator characteristic curve of 0.8 or more, after correcting for optimistic bias. We ranked the predictors by their F1-score, and those above a set threshold were compiled into a mobile app, Ebola CARE (Computational Assignment of Risk Estimates).Conclusions/SignificanceThis method demonstrates how to address small sample sizes and missing data, while creating predictive models that can be readily deployed to assist treatment in future outbreaks of EVD and other infectious diseases. By generating an ensemble of predictors instead of relying on a single model, we are able to handle situations where patient data is partially available. The prognosis app can be updated as new data become available, and we made all the computational protocols fully documented and open-sourced to encourage timely data sharing, independent validation, and development of better prediction models in outbreak response.

Rhabdomyolysis in Ebola Virus Disease. Results of an Observational Study in a Treatment Center in Guinea.

The pathogenesis of Ebola virus disease (EVD) remains unclear. The sporadic nature of Ebola outbreaks and their occurrence in resource-limited settings have precluded the acquisition of extensive clinical and laboratory data. Rhabdomyolysis during EVD has been suggested to occur in previous studies showing increased aspartate aminotransferase-alanine aminotransferase ratios, but, to date, has not been confirmed with creatine kinase (CK) assays. We performed an observational study of 38 patients admitted to an Ebola treatment center from January to April 2015. CK values from patients with confirmed EVD were compared with those in patients without confirmed EVD. A panel of other analyses were also performed. In patients with EVD, characteristics were compared between survivors and nonsurvivors. High levels of CK were more frequent in patients with EVD than in those without (P = .002), and rhabdomyolysis was more frequent (59% vs 19%, respectively; P = .03). CK levels >5000 U/L were observed in 36% of patients with EVD. Also in patients with EVD, fatal outcome was significantly associated with higher creatinine and bilirubin levels, international normalized ratio, and viral load. Rhabdomyolysis is a frequent disorder in EVD and seems to be more common than in other viral infections. It may contribute to the renal failure observed in nonsurviving patients. More studies are needed to determine the impact of rhabdomyolysis on EVD outcome.

Five cases report of Ebola virus disease

Objective To analyze the clinical characteristics, treatment and outcome of Ebola virus disease so as to provide early clinical recognition and treatment for this disease. Methods The clinical manifestations and treatment of 5 cases of Ebola virus disease in Ebola Holding Center of Sierra-Leone China Friendship Hospital from 15 March 2015 to 15 May 2015 were retrospectively analyzed. And the clinical characteristics and possible effective treatment were discussed combined with related literature. Results Five patients were diagnosed with Ebola virus disease by polymerase chain reaction and 4 cases of 5 patients had confirmed contact history, while 1 case had no clear contact history.All the 5 cases presented with low fever, headache and joint pain. Three cases then progressed into severe gastrointestinal symptoms such as nausea, vomiting, diarrhea and hypovolemic shock. The patients presented with fast heart rate and shortness of breath and other inflammatory response syndrome in acute phase. One patient rapidly progressed to liver pain, jaundice and anuria, then died. Three severe cases recovered after treated with fluid resuscitation, circulation maintenance and electrolyte balance in acute phase. Conclusions The early symptoms of Ebola virus disease are low fever, joint pain and nausea.Frequent vomiting, diarrhea, low blood pressure and electrolyte disorder indicate severe conditions. Shock and electrolyte disorder are deadly complications. Early recognition, diagnosis and treatment are the key to improve the prognosis. Key words: Ebolavirus; Hemorrhagic fever, Ebola; Shock; Water-electrolyte imbalance; Fluid therapy

Clinical characteristic analysis of 5 patients with confirmed Ebola virus disease

Objective To analyze the clinical characteristics and prognoses of patients with confirmed Ebola virus disease(EVD)and to summarize the clinical treatment experience.Methods The epidemiologic history,symptoms,signs,treatment,and prognoses of 5confirmed EVD cases were summarized.And the relationship between clinical features and clinical outcomes was analyzed.Results The 5patients,2 men and 3women,ranged in age from 32-58 years old,with a median age of 46.Three were severe cases when they were admitted while the others were relatively mild.All the patients admitted the exposure history within 21 days before onset of the symptoms,with two patients(one medical staff)from the same transmission chain.The main symptoms included fever,weakness or fatigue,lack of appetite,diarrhea and red eyes,with one patient having gastrointestinal bleeding.The first test of PCR Ebola virus(EBOV)RNA was positive in all the 5cases.They were promptly isolated and treated with antipyretic and fluid replacement therapy.Meanwhile,prevention of complications and treatment of basic diseases were also conducted.Three patients survived at last and the other two died.Conclusion Prompt isolation of the infection source and tracing the contacts can effectively prevent the transmission of EVD.PCR assay is an effective,rapid and simple method to diagnose EVD.Early supporting treatment-centered multimodality therapy can improve the treatment outcome of EVD.