Ebola Virus Disease Patients Research Articles

Development of a clinical prediction score for Ebola virus disease screening at triage centers in the Democratic Republic of the Congo.

The 2018-2020 Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) was the largest since the disease's discovery in 1976. Rapid identification and isolation of EVD patients are crucial during triage. This study aimed to develop a clinical prediction score for EVD using clinical and epidemiological predictors. We conducted a retrospective cross-sectional study using surveillance data from EVD outbreak, collected during routine clinical care at the Ebola Transit Center (ETC) in Beni, DRC, from 2018 to 2020. The Spiegelhalter and Knill-Jones method was used for score development, including potential predictors with an adjusted likelihood ratio above 2 or below 0.50. Validation was performed using a dataset previously published in PLOSOne by Tshomba et al. Among 3725 patients screened, 3698 fulfilled the inclusion criteria, with 571 (15.4%) testing positive for EVD via RT-PCR Test. Seven predictive factors were identified: asthenia, sore throat, conjunctivitis, bleeding gums, hematemesis, contact with a sick person, and contact with a traditional healer. The prediction score achieved an Area under the receiver operating characteristic (AUROC) of 0.764, with 81.4% sensitivity and 53.6% specificity at a -1 cutoff. External validation demonstrated an AUROC of 0.766, with 80.8% sensitivity and 41.4% specificity at the -1 cutoff. Our study developed a screening tool to assess the risk of suspected patients developing EVD and being admitted to ETUs for RT-PCR testing and treatment. External validation results affirmed the model's reliability and generalizability in similar settings, suggesting its potential integration into clinical practice. Given the severity and urgency of EVD as well as the risk nosocomial EVD transmission, it is essential to continuously update these models with real-time data on symptoms, disease progression, patient outcomes and validated RDT during EVD outbreaks. This approach will enhance model accuracy, enabling more precise risk assessments and more effective outbreak management.

Ebola virus-induced eye sequelae: a murine model for evaluating glycoprotein-targeting therapeutics

Ebola virus disease (EVD) survivors experience ocular sequelae including retinal lesions, cataracts, and vision loss. While monoclonal antibodies targeting the Ebola virus glycoprotein (EBOV-GP) have shown promise in improving prognosis, their effectiveness in mitigating ocular sequelae remains uncertain. We developed and characterized a BSL-2-compatible immunocompetent mouse model to evaluate therapeutics targeting EBOV-GP by inoculating neonatal mice with vesicular stomatitis virus expressing EBOV-GP (VSV-EBOV). To examine the impact of anti-EBOV-GP antibody treatment on acute retinitis and ocular sequelae, VSV-EBOV-infected mice were treated with polyclonal antibodies or monoclonal antibody preparations with antibody-dependent cellular cytotoxicity (ADCC-mAb) or neutralizing activity (NEUT-mAb). Treatment with all anti-EBOV-GP antibodies tested dramatically reduced viremia and improved survival. Further, all treatments reduced the incidence of cataracts. However, NEUT-mAb alone or in combination with ADCC-mAb reduced viral load in the eyes, downregulated the ocular immune and inflammatory responses, and minimized retinal damage more effectively. Anti-EBOV-GP antibodies can improve survival among EVD patients, but improved therapeutics are needed to reduce life altering sequelae. This animal model offers a new platform to examine the acute and long-term effect of the virus in the eye and the relative impact of therapeutic candidates targeting EBOV-GP. Results indicate that even antibodies that improve systemic viral clearance and survival can differ in their capacity to reduce acute ocular inflammation, and long-term retinal pathology and corneal degeneration. This study was partly supported by Postgraduate Research Fellowship Awards from ORISE through an interagency agreement between the US DOE and the US FDA.

Derivation and Internal Validation of a Mortality Prognostication Machine Learning Model in Ebola Virus Disease Based on Iterative Point-of-Care Biomarkers.

Although multiple prognostic models exist for Ebola virus disease mortality, few incorporate biomarkers, and none has used longitudinal point-of-care serum testing throughout Ebola treatment center care. This retrospective study evaluated adult patients with Ebola virus disease during the 10th outbreak in the Democratic Republic of Congo. Ebola virus cycle threshold (Ct; based on reverse transcriptase polymerase chain reaction) and point-of-care serum biomarker values were collected throughout Ebola treatment center care. Four iterative machine learning models were created for prognosis of mortality. The base model used age and admission Ct as predictors. Ct and biomarkers from treatment days 1 and 2, days 3 and 4, and days 5 and 6 associated with mortality were iteratively added to the model to yield mortality risk estimates. Receiver operating characteristic curves for each iteration provided period-specific areas under curve with 95% CIs. Of 310 cases positive for Ebola virus disease, mortality occurred in 46.5%. Biomarkers predictive of mortality were elevated creatinine kinase, aspartate aminotransferase, blood urea nitrogen (BUN), alanine aminotransferase, and potassium; low albumin during days 1 and 2; elevated C-reactive protein, BUN, and potassium during days 3 and 4; and elevated C-reactive protein and BUN during days 5 and 6. The area under curve substantially improved with each iteration: base model, 0.74 (95% CI, .69-.80); days 1 and 2, 0.84 (95% CI, .73-.94); days 3 and 4, 0.94 (95% CI, .88-1.0); and days 5 and 6, 0.96 (95% CI, .90-1.0). This is the first study to utilize iterative point-of-care biomarkers to derive dynamic prognostic mortality models. This novel approach demonstrates that utilizing biomarkers drastically improved prognostication up to 6 days into patient care.

Comparison of the performance of linear discriminant analysis and binary logistic regression applied to risk factors for mortality in Ebola virus disease patients

Our study aimed to identify risk factors associated with mortality in Ebola patients using binary logistic regression analysis and linear discriminant analysis, and to assess the predictive power of these two methods. Our study was a randomized, double-blind, controlled (observational) clinical trial conducted in 2018 during the 10th Ebola outbreak in eastern DRC. The study included 363 patients divided into two treatment arms, including 182 patients treated with MAB114 (Ebang) and 181 patients treated with REGENERON (REGN-EB3 ). After a thorough analysis of the data, both statistical analysis methods selected the same set of variables (risk factors) for the binary logistic regression we obtained: viral load 0.58 (0.5-0.67), creatinine 1.98 (1.58-0.67) and aspartate aminotransferase 0.99 (0.9-1); as for the linear discriminant analysis we have viral load (0.88), creatinine (0.94) and aspartate aminotransferase (0.78). We also see almost the same results when different prediction probabilities are evaluated. Logistic regression predicted a mortality rate of 36.5% and linear discriminant analysis predicted a mortality rate of 38.8%. Using the AUC (area under the curve) score, we were able to evaluate two methods and obtain a score of 0.935 for the binary logistic regression and 0.932 for the linear discriminant analysis. According to the evaluation hypothesis, both methods give the same risk factors (viral load (Ctnp), creatinine and alanine aminotransferase (ALT)) with a probability of 93%.

A review on ebola virus

The Ebola virus of the Filoviridae family is the cause of Ebola virus disease (EVD), a deadly viral hemorrhagic sickness. Due to the prevalence of immigrants, the disease has become a global public health threat. The victims initially exhibit vague influenza-like symptoms before succumbing to shock and multiorgan failure. There is no established procedure for treating EVD; instead, only supportive and symptomatic therapy is used. The Ebola virus, including its clinical and oral symptoms, diagnostic tools, differential diagnoses, preventive measures, and management protocol, are thoroughly discussed in this review paper. Since then, the Ebola virus has occasionally started to infect humans, causing multiple epidemics. The expansion of the Ebola virus has resulted in the deadliest diseases for both animals and humans because of the growth of urbanization, invasion of forested areas, and intimate contact with wildlife creatures. The Ebola virus disease (EVD) has so far claimed the lives of numerous people, with an increased number of cases being seen throughout the African continent. Thus, a study was conducted to evaluate the efficacy and safety of medications approved for the treatment of EVD, trends in EVD outbreaks, morbidity and mortality among EVD patients, and other factors.

Ebola outbreak in Guinea, 2021: Clinical care of patients with Ebola virus disease.

Experience from the Zaire Ebolavirus epidemic in the eastern Democratic Republic of the Congo (2018-2020) demonstrates that early initiation of essential critical care and administration of Zaire Ebolavirus specific monoclonal antibodies may be associated with improved outcomes among patients with Ebola virus disease (EVD). This series describes 13 EVD patients and 276 patients with suspected EVD treated during a Zaire Ebolavirus outbreak in Guinea in 2021. Patients with confirmed or suspected EVD were treated in two Ebola treatment centres (ETC) in the region of N'zérékoré. Data were reviewed from all patients with suspected or confirmed EVD hospitalised in these two ETCs during the outbreak (14 February 2021 - 19 June 2021). Ebola-specific monoclonal antibodies, were available 2 weeks after onset of the outbreak. Nine of the 13 EVD patients (age range: 22-70 years) survived. The four EVD patients who died, including one pregnant woman, presented with multi-organ dysfunction and died within 48 h of admission. All eight patients who received Ebola-specific monoclonal antibodies survived. Four of the 13 EVD patients were health workers. Improvement of ETC design facilitated implementation of WHO-recommended 'optimized supportive care for EVD'. In this context, pragmatic clinical training was integrated in routine ETC activities. Initial clinical manifestations of 13 confirmed EVD patients were similar to those of 276 patients with suspected, but subsequently non confirmed EVD. These patients suffered from other acute infections (e.g. malaria in 183 of 276 patients; 66%). Five of the 276 patients with suspected EVD died. One of these five patients had Lassa virus disease and a coronavirus disease 2019 (COVID-19) co-infection. Multidisciplinary outbreak response teams can rapidly optimise ETC design. Trained clinical teams can provide WHO-recommended optimised supportive care, including safe administration of Ebola-specific monoclonal antibodies. Pragmatic training in essential critical care can be integrated in routine ETC activities. This article describes clinical realities associated with implementation of WHO-recommended standards of 'optimized supportive care' and administration of Ebola virus specific treatments. In this context, the importance of essential design principles of ETCs is underlined, which allow continuous visual contact and verbal interaction of health workers and families with their patients. Elements that may contribute to further quality of care improvements for patients with confirmed or suspected EVD are discussed.

Development and Clinical Evaluation of a Rapid Point of Care Test for Ebola Virus Infection in Humans.

The genus Ebolavirus contains multiple species of viruses that are highly contagious and lethal, often causing severe hemorrhagic fever. To minimize the global threat from Ebola virus disease (EVD), sustainable, field-appropriate tools are needed to quickly screen and triage symptomatic patients and conduct rapid screening of cadavers to ensure proper handling of human remains. The OraQuick® Ebola Rapid Antigen Test is an in vitro diagnostic single-use immunoassay for the qualitative detection of Ebola virus antigens that detects all known species within the genus Ebolavirus. Here, we report the performance of the OraQuick® Ebola Rapid Antigen Test and provide a comparison of its performance with other rapid diagnostic tests (RDTs) for EVD. OraQuick® Ebola demonstrated clinical sensitivity of 84.0% in archived EVD patient venous whole-blood (WB) samples, 90.9% in Ebola virus-infected monkey fingerstick samples, and 97.1% in EVD patient cadaver buccal swabs, as well as clinical specificity of 98.0-100% in venous WB samples and 99.1-100% in contrived saliva samples. It is the only 510(k)-cleared Ebola rapid test, has analytical sensitivity as good as or better than all RDT comparators for EVD, and can detect the Sudan virus. Our data demonstrate that the OraQuick® Ebola Rapid Antigen Test is a sensitive and specific assay that can be used for rapid detection of EBOV in humans and could support efforts for EVD-specific interventions and control over outbreaks.

Development of the PREDS score to predict in-hospital mortality of patients with Ebola virus disease under advanced supportive care: Results from the EVISTA cohort in the Democratic Republic of the Congo.

SummaryBackgroundAs mortality remains high for patients with Ebola virus disease (EVD) despite new treatment options, the ability to level up the provided supportive care and to predict the risk of death is of major importance. This analysis of the EVISTA cohort aims to describe advanced supportive care provided to EVD patients in the Democratic Republic of the Congo (DRC) and to develop a simple risk score for predicting in-hospital death, called PREDS.MethodsIn this prospective cohort (NCT04815175), patients were recruited during the 10th EVD outbreak in the DRC across three Ebola Treatment Centers (ETCs). Demographic, clinical, biological, virological and treatment data were collected. We evaluated factors known to affect the risk of in-hospital death and applied univariate and multivariate Cox proportional-hazards analyses to derive the risk score in a training dataset. We validated the score in an internal-validation dataset, applying C-statistics as a measure of discrimination.FindingsBetween August 1st 2018 and December 31th 2019, 711 patients were enrolled in the study. Regarding supportive care, patients received vasopressive drug (n = 111), blood transfusion (n = 101), oxygen therapy (n = 250) and cardio-pulmonary ultrasound (n = 15). Overall, 323 (45%) patients died before day 28. Six independent prognostic factors were identified (ALT, creatinine, modified NEWS2 score, viral load, age and symptom duration). The final score range from 0 to 13 points, with a good concordance (C = 86.24%) and calibration with the Hosmer-Lemeshow test (p = 0.12).InterpretationThe implementation of advanced supportive care is possible for EVD patients in emergency settings. PREDS is a simple, accurate tool that could help in orienting early advanced care for at-risk patients after external validation.FundingThis study was funded by ALIMA.

Ebola virus infection induces a delayed type I IFN response in bystander cells and the shutdown of key liver genes in human iPSC-derived hepatocytes.

SummaryLiver damage and an exacerbated inflammatory response are hallmarks of Ebola virus (EBOV) infection. Little is known about the intrinsic response to infection in human hepatocytes and their contribution to inflammation. Here, we present an induced pluripotent stem cell (iPSC)-derived hepatocyte-like cell (HLC) platform to define the hepato-intrinsic response to EBOV infection. We used this platform to show robust EBOV infection, with characteristic ultrastructural changes and evidence for viral replication. Transcriptomics analysis revealed a delayed response with minimal early transcriptomic changes, followed by a general downregulation of hepatic function and upregulation of interferon signaling, providing a potential mechanism by which hepatocytes participate in disease severity and liver damage. Using RNA-fluorescence in situ hybridization (FISH), we showed that IFNB1 and CXCL10 were mainly expressed in non-infected bystander cells. We did not observe an inflammatory signature during infection. In conclusion, iPSC-HLCs are an immune competent platform to study responses to EBOV infection.

Virus kinetics and biochemical derangements among children with Ebolavirus disease.

SummaryBackgroundA paucity of data is available on virologic and biochemical characteristics of paediatric Ebolavirus disease (EVD), compared to adults.MethodsWe conducted a retrospective chart review of children (<16 years old) and a comparator group of young adults (16–44 years) from two treatment centres during the 2018–2020 EVD epidemic in Eastern Democratic Republic of the Congo. Statistical methods included chi-squared and Fisher's exact tests (dichotomous and categorical variables), Mann-Whitney U-test (continuous variables), multivariable linear regression (for determinants of admission viral load), linear mixed-effects models (for analysis of longitudinal viral load), and Cox proportional hazard models (to examine risk factors for mortality).FindingsWe included 73 children and 234 adults admitted from April to October 2019. Paediatric patients commonly had electrolytes imbalances: hypokalaemia in 26/73 (36%), hyperkalaemia in 38/73 (52%), and hyponatraemia in 54/73 (74%). Hypoglycaemia occurred in 20/73 (27%), acute kidney injury in 43/73 (59%), and rhabdomyolysis in 35/73 (48%). Biochemical abnormalities were detected in a similar proportion of children and adults. The viral load (VL, log10 copies/mL) at admission (7.2 versus 6.5, p=0.0001), the peak viral load (7.5 versus 6.7, p=<0.0001), and the time for viraemia clearance (16 days versus 12 days, p=<0.0001) were significantly different in children. The duration of hospital stay was prolonged in children (20 versus 16 days, p=<0.0001). Risk factors for mortality in children were: VL >7.6 log10copies/mL, alanine transaminase >525 U/L, C-reactive protein >100 mg/L, blood urea nitrogen >7.5 mmol/L, rhabdomyolysis, and.acute kidney injury.InterpretationPaediatric EVD patients, like adults, experience multiorgan dysfunction with life-threatening electrolyte imbalances, hypoglycaemia, kidney injury, liver injury, and rhabdomyolysis. Paediatric patients have significantly higher VLs throughout the course of EVD than adults.FundingThis study was not funded.

Added Value of an Anti-Ebola Serology for the Management of Clinically Suspected Ebola Virus Disease Patients Discharged as Negative in an Epidemic Context.

BackgroundSurvivors from Ebola virus disease (EVD) may be at the origin of EVD resurgence.MethodsSimultaneous reactivity to at least 2 Ebola virus or Zaire ebolavirus (EBOV) antigens was detected in 11 of 488 (2.3%; 95% confidence interval [CI], 1.1–4.0) suspected EVD patients who were discharged as negative after 2 consecutive negative tests during the 10th Ebola outbreak in the Democratic Republic of the Congo.ResultsAfter extrapolating the total number of individuals discharged as negative during the entire outbreak, we estimated a total of 1314 additional missed Ebola cases.ConclusionsThese findings emphasize the usefulness of an EBOV serology analysis and the importance of extending epidemic surveillance to clinically suspected cases who were discharged as negative.

Association between oral antimalarial medication administration and mortality among patients with Ebola virus disease: a multisite cohort study

BackgroundEmpiric antimalarial treatment is a component of protocol-based management of Ebola virus disease (EVD), yet this approach has limited clinical evidence for patient-centered benefits.MethodsThis retrospective cohort study evaluated the association between antimalarial treatment and mortality among patients with confirmed EVD. The data was collected from five International Medical Corps operated Ebola Treatment Units (ETUs) in Sierra Leone and Liberia from 2014 through 2015. The standardized protocol used for patient care included empiric oral treatment with combination artemether and lumefantrine, twice daily for three days; however, only a subset of patients received treatment due to resource variability. The outcome of interest was mortality, comparing patients treated with oral antimalarials within 48-h of admission to those not treated. Analysis was conducted with logistic regression to generate adjusted odds ratios (aORs). Multivariable analyses controlled for ETU country, malaria rapid diagnostic test result, age, EVD cycle threshold value, symptoms of bleeding, diarrhea, dysphagia and dyspnea, and additional standard clinical treatments.ResultsAmong the 424 cases analyzed, 376 (88.7%) received early oral antimalarials. Across all cases, mortality occurred in 57.5% (244). In comparing unadjusted mortality prevalence, early antimalarial treated cases yielded 55.1% mortality versus 77.1% mortality for those untreated (p = 0.005). Multivariable analysis demonstrated evidence of reduced aOR for mortality with early oral antimalarial treatment versus non-treatment (aOR = 0.34, 95% Confidence Interval: 0.12, 0.92, p = 0.039).ConclusionEarly oral antimalarial treatment in an EVD outbreak was associated with reduced mortality. Further study is warranted to investigate this association between early oral antimalarial treatment and mortality in EVD patients.

Expanded Histopathology and Tropism of Ebola Virus in the Rhesus Macaque Model: Potential for Sexual Transmission, Altered Adrenomedullary Hormone Production, and Early Viral Replication in Liver

The pathogenesis of Ebola virus disease (EVD) is still incomplete, in spite of the availability of a nonhuman primate modelfor more than 4 decades. To further investigate EVD pathogenesis, a natural history study was conducted using 27 Chinese-origin rhesus macaques. Of these, 24 macaques were exposed intramuscularly to Kikwit Ebola virus and euthanized at predetermined time points or when end-stage clinical disease criteria were met, and 3 sham-exposed macaques were euthanized on study day 0. This study showed for the first time that Ebola virus causes uterine cervicitis, vaginitis, posthitis, and medullary adrenalitis. Not only was Ebola virus detected in the interstitial stromal cells of the genital tract, but it was also present in the epididymal and seminal vesicular tubular epithelial cells, ectocervical and vaginal squamous epithelial cells, and seminal fluid. Furthermore, as early as day 3 after exposure, Ebola virus replicative intermediate RNA was detected in Kupffer cells and hepatocytes. These findings in the nonhuman model provide additional insight into potential sexual transmission, possible disruption of sympathetic hormone production, and early virus replication sites in human EVD patients.

Post-exposure prophylaxis following high-risk contact with Ebola virus, using immunotherapies with monoclonal antibodies, in the eastern Democratic Republic of the Congo: an emergency use program

IntroductionWith the development of therapeutics and vaccine against Ebola virus disease (EVD), the question of post-exposure prophylaxis for high-risk contact has emerged. Immunotherapies (monoclonal antibodies [mAbs]) recently validated for treating infected patients appear to be a good candidate for protecting contacts. DesignDuring the tenth EVD outbreak in the Democratic Republic of the Congo, we have administrated mAbs (Mab114 or REGN-EB3) to high and intermediate-risk contacts of EVD patients. Results: Overall, 23 non-vaccinated contacts received mAbs after a median delay between contact and post-exposure prophylaxis of 1 day (interquartile range 1–2). All contacts were free of symptoms, and all had negative reverse transcriptase-polymerase chain reaction 14 days after the contact. ConclusionImmunotherapies appear to be promising candidates to protect EVD contacts. Interaction with vaccine needs to be analyzed and a larger study on efficacy conducted.

Review: Insights on Current FDA-Approved Monoclonal Antibodies Against Ebola Virus Infection.

The unprecedented 2013-2016 West Africa Ebola outbreak accelerated several medical countermeasures (MCMs) against Ebola virus disease (EVD). Several investigational products (IPs) were used throughout the outbreak but were not conclusive for efficacy results. Only the Randomized Controlled Trial (RCT) on ZMapp was promising but inconclusive. More recently, during the second-largest Ebola outbreak in North Kivu and Ituri provinces, Democratic Republic of the Congo (DRC), four IPs, including one small molecule (Remdesivir), two monoclonal antibody (mAb) cocktails (ZMapp and REGN-EB3) and a single mAb (mAb114), were evaluated in an RCT, the Pamoja Tulinde Maisha (PALM) study. Two products (REGN-EB3 and mAb114) demonstrated efficacy as compared to the control arm, ZMapp. There were remarkably few side effects recorded in the trial. The FDA approved both medications in this scientifically sound study, marking a watershed moment in the field of EVD therapy. These products can be produced relatively inexpensively and can be stockpiled. The administration of mAbs in EVD patients appears to be safe and effective, while several critical knowledge gaps remain; the impact of early administration of Ebola-specific mAbs on developing a robust immune response for future Ebola virus exposure is unknown. The viral mutation escape, leading to resistance, presents a potential limitation for single mAb therapy; further improvements need to be explored. Understanding the contribution of Fc-mediated antibody functions such as antibody-dependent cellular cytotoxicity (ADCC) of those approved mAbs is still critical. The potential merit of combination therapy and post-exposure prophylaxis (PEP) need to be demonstrated. Furthermore, the PALM trial has accounted for 30% of mortality despite the administration of specific treatments. The putative role of EBOV soluble Glycoprotein (sGP) as a decoy to the immune system, the virus persistence, and relapses might be investigated for treatment failure. The development of pan-filovirus or pan-species mAbs remains essential for protection. The interaction between FDA-approved mAbs and vaccines remains unclear and needs to be investigated. In this review, we summarize the efficacy and safety results of the PALM study and review current research questions for the further development of mAbs in pre-exposure or emergency post-exposure use.

Knowledge, Attitude and Practice of Sudanese Health Care Providers toward Ebola Virus Outbreak.

Ebola virus disease (EVD) is a highly contagious and fatal disease in humans. Healthcare providers (HCPs) are often at the frontline of epidemics and can thus be in jeopardy of contracting EVD. Sudan is at a great risk of an EVD outbreak, as it borders countries that experienced EVD outbreaks. It is therefore imperative in Sudan to assess the HCPs' awareness and knowledge, attitude, and practice (KAP) about EVD for its control and man-agement and for preparedness. A KAP survey was conducted among 387 HCPs (physicians, nurses and labora-tory technicians) in the three main tertiary hospitals in Khartoum, Sudan. The majority of the survey respon-dents (54.5%) were females, < 30 years old (76.3%), and single (77.4%). Most (94%) had heard about EVD, 62% from classical media. Only 14% had received education or training regarding EVD. About 40% reported being adherent to universal precautions and 72% were willing to deal with EVD patients under safety precau-tions. Only 10% knew of any available standard national guidelines for EVD. Nearly half of the HCPs (47%) rated the potential risk of an EVD outbreak in Sudan as high, and 52% rated health authorities' effort against it as weak. These findings revealed the HCPs' insufficient knowledge of EVD and the necessary universal precau-tions. This lack of knowledge would negatively affect the HCPs' preparedness toward any potential EVD out-break. There is a dire need to train HCPs in Sudan on the management of EVD, including preventive and con-trol measures.

Factors associated with length of stay and treatment outcome of Ebola patients treated at an Ebola treatment center in Sierra Leone during the peak period of the West African Ebola outbreak 2013\u20132016

BackgroundThe World Health Organization (WHO) declared the West Africa Ebola epidemic as a Public Health Emergency of International Concern in August 2014. During the outbreak period, there were calls for the affected countries to construct Ebola treatment centres and reliable diagnostic laboratories closer to areas of transmission in order to improve the quality care of Ebola Virus Disease (EVD) patients. Delay in seeking treatment has been reported to have led to poor treatment outcome of EVD patients. Sierra Leone recorded more than 8000 probable and confirmed cases and more than 4000 EVD -related deaths nation-wide.MethodsIn this retrospective study, we investigated the effects of treatment delay, length of symptomatic period, EVD patients’ sex, age, occupation, region of residence, and clinical characteristics on the treatment outcome of 205 laboratory-confirmed EVD patients who were admitted at the Kenema Government Hospital Ebola Treatment Center (KGHETC) from 13/09/2014–26/11/2014; i.e. during the peak of 2013–2016 EVD outbreak in Sierra Leone. Specifically also, we determined the factors that were associated with the length of stay for EVD treatment for patients who were discharged alive.ResultsMajority (66.3%, n = 205/309) of the 309 suspected EVD patients with medical records at the KGHETC triage during the period under review were tested positive for EVD using reverse-transcriptase-polymerase chain reaction (RT-PCR) and had a definitive treatment outcome. Few (33.7%, n = 104/309) suspected EVD patients were not included in our analysis and were classified thus: 29.1% (n = 90/309) suspect EVD cases with negative RT-PCR results, 4.5% (n = 14/309) suspect cases with non-available RT-PCR result.Of the 205 patients, 99 (48.3%) had a fatal outcome. For EVD patients that survived, we recorded a significant association (− 0.06, 95% Confidence Interval (CI) = − 0.14 – - 0.02, p = 0.004) between the Length of Stay (LOS) and for each kilometer travelled to seek treatment at the KGHETC. However, the association between EVD patients that were low skilled workers (− 5.91, 95% CI = − 24.60 – 12.79, p = 0.73), EVD patients who were children and pupils in junior school (− 0.86, 95% CI = − 12.86 – 11.14, p = 0.73), health seeking delay for EVD patients who resided in Kenema District where the KGHETC was located (− 0.49, 95% CI = − 0.12 – 1.09, p = 0.24), sex (− 1.77, 95% CI = − 8.75 – 5.21, p = 0.50), age (0.21, 95% CI = − 0.36 – 0.77, p = 0.57), referral status (1.21, 95% CI = − 17.67 – 20.09, p = 0.89) and the LOS in surviving patients were not statistically significant.ConclusionThe high LOS for either treatment outcome for EVD patients that resided in the district in which the EVD treatment facility was located compared to those patients from other districts implies that health authorities should consider intensive health education with high priority given to seeking early EVD treatment, and the construction of strategic ETCs as important components in their response strategy.

Dying in honour: experiences of end-of-life palliative care during the 2013\u20132016 Ebola outbreak in Guinea

With no cure and a high mortality rate, Ebola virus disease (EVD) outbreaks require preparedness for the provision of end-of-life palliative care. This qualitative study is part of a larger project on palliative care in humanitarian contexts. Its goal was to document and deepen understanding of experiences and expectations related to end-of-life palliative care for patients infected with Ebola virus disease (EVD) in West African Ebola treatment centres (ETCs) during the 2013–2016 epidemic. It consisted of 15 in-depth semi-structured interviews with individuals impacted by EVD in a Guinean ETC: either as patients in an ETC, healthcare providers, healthcare providers who were also EVD patients at one point, family relations who visited patients who died in an ETC, or providers of spiritual support to patients and family. Analysis was team based and applied an interpretive descriptive approach. Healthcare delivery in humanitarian emergencies must remain respectful of patient preferences but also local and contextual values and norms. Of key importance in the Guinean context is the culturally valued experience of “dying in honour”. This involves accompaniment to facilitate a peaceful death, the possibility of passing on final messages to family members, prayer, and particular practices to enact respect for the bodies of the deceased. Participants emphasized several challenges to such death in Ebola treatment centres (ETCs), as well as practices they deemed helpful to alleviating dying patients’ suffering. An overarching message in participants’ accounts was that ideally more would have been done for the dying in ETCs. Building on participants’ accounts, we outline a number of considerations for optimizing end-of-life palliative care during current and future public health emergencies, including for COVID-19.

Viral Load in Non-Surviving Liberian Ebola Virus Disease Patients Is Underestimated by Diagnostic qRT-PCR: A Retrospective Observational Study

Background: Viral load in Ebola virus disease (EVD) correlates with case fatality rate (CFR) and is an important parameter used for diagnostic cutoffs, stratification in randomized controlled trials, and epidemiologic investigation. However, it is currently only estimated using cycle threshold (Ct) values from diagnostic qRT-PCR tests that were not developed or validated for quantitative purposes. Furthermore, during the 2013-2016 EVD epidemic in west Africa, numerous different diagnostic platforms and protocols were used and yielded inconsistent, often conflicting data. Methods: 727 whole blood samples, both positive and negative for Ebola virus (EBOV), that were collected for diagnostic purposes in Monrovia, Liberia between August 28 and December 18, 2014 were reanalyzed under highly controlled biosafety level 4 laboratory conditions. An optimized TRIzol-based extraction protocol was utilized, followed by a novel semi-strand specific two-step droplet digital PCR assay to quantify viral load as log10 EBOV RNA copies/mL. These data were then compared to the cycle threshold (Ct) values from the original diagnostic qRT-PCR testing, and a subset of the samples was also reanalyzed following re-extraction with the same diagnostic one-step PCR and instruments employed at the Ebola treatment unit for further assessment. Finally, for EBOV-positive patients, correlations between viral load, outcome, time from symptom onset, and other epidemiological parameters were evaluated utilizing a deidentified database. Findings: Survivors had significantly lower mean viral loads at presentation than non-survivors in both the reanalyzed dataset (5.61 [95% CI 5.34 to 5.87] versus 7.19 [95% CI 6.99 to 7.38] log10 EBOV RNA copies/mL, respectively; p < 0.0001) and diagnostic dataset (Ctvalue 28.72 [95% CI 27.97 to 29.47] versus 26.26 [95% CI 25.72 to 26.81], respectively; p < 0.0001). However, receiver operating characteristic curve analysis demonstrated the reanalyzed dataset to be superior to the diagnostic dataset (area under curve 0.80 [95% CI 0.75 to 0.85] versus 0.66 [95% CI 0.59 to 0.72], respectively) in distinguishing between survivors and non-survivors and the prognostic capacity of viral load increased substantially upon reanalysis (odds ratio [OR] of death 8.06, 95% CI 4.81 to 13.53, p < 0.0001 for viral loads above 6.71 log10 EBOV RNA copies/mL versus OR of death 2.02, 95% CI 1.27 to 3.20, p = 0.0028 for Ct values below 27.37). Diagnostic Ct values underestimated viral load in non-survivors by nearly 100-fold on average (mean difference between diagnostic Ct value and reanalyzed Ct value of 5.15 [95% CI 4.43 to 5.87]); substantially less discrepancy was observed for survivors (mean difference between diagnostic Ct value and reanalyzed Ct value of 1.79 [95% CI 1.16 to 2.43]). Six samples that were reported negative by diagnostic testing were found to be positive upon reanalysis, and had high viral loads. Non-survivors presented to the ETU significantly earlier as the epidemic progressed, from 6.8 days following symptom onset (95% CI 5.7 to 7.9), on average, during the first three weeks to 3.7 days (95% CI 2.4 to 5.0) during the last three weeks (p = 0.0006) and had significantly lower viral loads (7.6 log10 EBOV RNA copies/mL [95% CI 7.3 to 7.9] to 6.5 log10 EBOV RNA copies/mL [95% CI 5.8 to 7.2] for the same intervals (p = 0.0046). However, the CFR remained steady at approximately 60% throughout. Interpretation: Inaccurate viral load estimation from diagnostic Ct values is likely multifactorial, but unaddressed PCR inhibition from tissue damage in patients with fulminant EVD may largely account for the discrepancies between the datasets in this study. In light of these findings, testing protocols for EVD require further standardization and validation to produce accurate viral load estimates, minimize false negatives, and allow for reliable epidemiological investigation. Funding Information: This research was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The deidentified samples and data utilized for this study received a determination of ‘not human subjects research’ by the NIH Office of Human Subjects Research Protection and has been approved by the University of Liberia-Pacific Institute for Research and Evaluation IRB.

Guidance materials from 2014 to 2019 on nutritional care for Ebola patients in Ebola Treatment Units: an analysis.

To evaluate the inclusion and exclusion of nutritional content in guidance materials related to nutritional care for hospitalised Ebola Virus Disease (EVD) patients of any age with the aim to provide recommendations for future revised nutritional care guidelines in Ebola Treatment Units (ETU). Qualitative and quantitative analyses of ETU protocols and other guidance materials were conducted. Materials were obtained from practitioners, their organisations and governments active in EVD outbreaks since 2014. Guinea, Liberia, Sierra Leone and Democratic Republic of Congo. Guidance materials showed a wide variety of topics. Most contained information on different feeding phases during illness, the use of specialised products, what and how to feed children aged 0-23 months, and meal and snack frequency for different age groups. Most materials lacked guidance on how to assess or accommodate patients' dietary preferences, how to obtain feedback on nutritional care from patients or how to assess whether patients need feeding support. These aspects are particularly relevant to prevent deterioration of the patients' nutritional status. There was limited guidance on operational aspects of food preparation and provision. Since 2014, numerous materials have been developed by organisations and governments on nutritional support in ETU. Although every EVD outbreak response must be contextualised because of the complexity of EVD and its case management, it is important to resolve technical differences and to provide comprehensive and more practical guidance. The findings of this study may inform future revised guidelines from normative UN organisations and governments of countries affected by EVD.