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

Background: 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). Objectives: This series describes 13 EVD patients and 276 patients with suspected EVD treated during a Zaire Ebolavirus outbreak in Guinea in 2021. Method: 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. Results: 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. Conclusion: 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. Contribution: 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.

Virus kinetics and biochemical derangements among children with Ebolavirus disease.

Background: A paucity of data is available on virologic and biochemical characteristics of paediatric Ebolavirus disease (EVD), compared to adults. Methods: We 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). Findings: We 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. Interpretation: Paediatric 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. Funding: This study was not funded.

Perceptions of ebola virus disease among the bambuti hunter group: a mixed-methods study.

The second largest Ebola virus disease (EVD) epidemic occurred in the Democratic Republic of the Congo (DRC) from 2018-20. The Bambuti, a hunter population in the Ituri Forest of the DRC, may be vulnerable to the zoonotic spread of EVD due to their frequent handling of forest animals. We conducted five focus group discussions and surveyed 113 Bambuti and 91 Bantu (control group), to discern how the Bambuti perceived and responded to EVD. Thematic analysis of focus group discussions revealed three major themes: (1) deprivation and discrimination; (2) mistrust; and (3) epistemic dissonance with public health messages emphasizing risks posed by forest animals. In surveys, 98% of Bambuti were deprived using the multidimensional poverty index (versus 78% of Bantu controls, p < 0.0001) and 77% had no formal education (versus 29% of controls, p < 0.0001). Bambuti were more dependent on wild meat for survival (51% versus 32% of controls, p = 0.008) and more frequently opposed the implementation of a bushmeat ban (48% versus 19% of controls, p < 0.0001). Trust in government was similar among Bambuti and Bantu. Comprehensive EVD knowledge was poor overall, and lower among the Bambuti (2% versus 8% of controls, p = 0.041). Compliance with public health measures was associated with higher levels of education and trust in government but did not differ between Bambuti and Bantu survey respondents. Together, our findings point to a particular vulnerability of the Bambuti to the effects of EVD, attributable at least in part to multidimensional poverty.

Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine.

Ebolavirus Disease (EVD) is a severe haemorrhagic fever that occurs in epidemic outbreaks, with a high fatality rate and no specific therapies available. rVSVΔG-ZEBOV-GP (Ervebo®), a live-attenuated recombinant vesicular stomatitis virus vector expressing the glycoprotein G of Zaire Ebolavirus, is the first vaccine approved for prevention of EVD. Both innate and adaptive responses are deemed to be involved in vaccine-induced protection, yet the mechanisms are not fully elucidated. A global transcriptomic approach was used to profile the blood host-response in 51 healthy volunteers enrolled in a phase 1/2 clinical trial. Signatures of the host responses were investigated assessing the enrichment in differentially expressed genes (DEGs) of specific "blood transcription modules" (BTM). Comparison of gene-expression levels showed that vaccination produces a peak of 5469 DEGs at day one, representing 38.6% of the expressed genes. Out of 346 BTMs, 144 were significantly affected by vaccination. Innate immunity pathways were induced from day 1 to day 14. At days 2 and 3, neutrophil modules were downregulated and complement-related modules upregulated. T-cell and cell-cycle associated modules were upregulated at days 7 and 14, while at day 28, no modules remained activated. At day 14, a direct correlation was observed between ZEBOV glycoprotein-specific antibody titres and activation of seven BTMs, including two related to B-cell activation and B cell receptor signalling. Transcriptomic analysis identified an rVSVΔG-ZEBOV-GP-induced signature and demonstrated a direct correlation of blood transcriptomic changes with ZEBOV glycoprotein-specific antibody titres.

Ebola: A review and focus on neurologic manifestations.

Ebolavirus disease (EVD) is a severe, highly contagious, and often fatal systemic disease in human and non-human primates. Zoonotic and human-to-human transmission have been well documented. Ebolaviruses are endemic to Equatorial and West Africa and there have been over 20 outbreaks in sub-Saharan Africa since 1976. The largest known outbreak of EVD occurred between 2013 and 2016 across several West African countries. It resulted in 28,646 suspected and confirmed cases and 11,323 deaths. There are 5 species within the genus Ebolavirus with 4 of them being clinically significant. In patients with EVD, neurologic manifestations range from mild symptoms such as confusion to severe neurologic diseases such as meningitis and encephalitis. Altered mental status, from mild confusion to delirium with hallucinations, may also occur. Rare neuropsychiatric manifestations of EVD include psychological or cognitive symptoms, including short-term memory loss, insomnia, and depression or anxiety. Although Ebolavirus RNA has been detected in cerebrospinal fluid, the body of knowledge around the pathogenic mechanisms of neurological disease is not yet fully understood. Studies are needed to understand the acute and chronic neuronal pathologic as well as biochemical cerebrospinal fluid changes in Ebolavirus infection.

Factores pronósticos clínicos determinantes en la supervivencia de pacientes con el virus Ébola / Clinical prognostic factors determining the survival of patients with the Ebola virus

Introducción: La enfermedad por el virus del Ébola presenta una elevada letalidad, por lo cual resulta de gran interés la realización de investigaciones que aborden las manifestaciones clínicas que pudieran ser factores pronósticos de supervivencia. Objetivo: Evaluar factores pronósticos de los pacientes enfermos de ébola. Métodos: El universo lo constituyó la totalidad (n = 350) de pacientes ingresados. Se emplearon medidas de resumen para variables cualitativas, estimaciones puntuales y por intervalos para las cuantitativas, así como las pruebas de significación Kaplan-Meier, regresión de Cox y Odds Ratio. Se trabajó con un nivel de confiabilidad del 95 por ciento. Resultados: La supervivencia global fue del 42,5 por ciento. La media de supervivencia, de aproximadamente 10 días (IC: 9 - 11 días). Los pacientes que ingresaron en estado grave (OR = 3,76), que tuvieron dolor lumbar (OR = 2,24), que refirieron cefalea (OR = 2,22), que presentaron fiebre (OR=2,16), que aquejaron de dolor abdominal (OR=1,95) y a quienes se les constató inyección conjuntival (OR = 1,86), tuvieron mayor probabilidad de fallecer, que quienes ingresaron sin estos síntomas y signos. Conclusiones: La supervivencia fue elevada, pese a las complicaciones presentadas. Los síntomas y signos predictores de muerte en los pacientes fueron: la gravedad del paciente al momento del ingreso, la presencia de dolor lumbar, cefalea, fiebre, dolor abdominal e inyección conjuntival(AU)

Introduction: Ebola virus disease has a high lethality, which is why it is of great interest to carry out research that addresses clinical manifestations that could be prognostic factors for survival. Objective: To evaluate prognostic factors of Ebola patients. Methods: the universe was constituted by the totality (n = 350) of admitted patients. Summary measures were used for qualitative variables, point and interval estimates for quantitative variables, as well as Kaplan-Meier significance tests, Cox regression and Odds Ratio. We worked with a 95% level of reliability. Results: The overall survival was 42.5 por ciento. The average survival, approximately 10 days (CI: 9-11 days). Patients who were admitted in serious condition (OR = 3.76), who had low back pain (OR = 2.24), who reported headache (OR = 2.22), who presented fever (OR = 2.16), who they suffered from abdominal pain (OR = 1.95) and who were found to have conjunctival injection (OR = 1.86), were more likely to die than those who entered without these symptoms and signs. Conclusions: Survival was high, despite the complications presented. The symptoms and predictive signs of death in the patients were: the severity of the patient at admission, the presence of low back pain, headache, fever, abdominal pain and conjunctival injection(AU)

Examination of the effect of agitation on the potency of the Ebola Zaire vaccine rVSVΔG-ZEBOV-GP.

The Ebolavirus vaccine (rVSVΔG-ZEBOV-GP) is stored at -80 to -60 °C and should be kept frozen for transport. Due to significant logistical challenges, frozen transport is not feasible for some remote locations. To determine if local distribution at 2-8 °C is a potential option for these locations, a study was conducted to evaluate the impact of agitation on the thawed vaccine. After up to 7 days of constant agitation, no impact on vaccine potency was evident for the agitated vaccine versus the corresponding vaccine kept stationary at 2-8 °C. In conclusion, in-country transport of the Ebolavirus vaccine, rVSVΔG-ZEBOV-GP, at 2-8 °C appears to be a feasible option for those remote locations where significant logistical challenges prohibit transporting the vaccine at -80 to -60 °C.

A Brief History of Ebolavirus Disease: Paving the Way Forward by Learning from the Previous Outbreaks.

In this review, Ebolavirus Disease (EVD) outbreaks have been comprehensively reviewed from their beginning until now. It chronologically discusses how each outbreak was tackled, national and international actions taken, diagnostic methods applied, the infection control procedures put in place, and the lessons learnt from each epidemic for the control of subsequent epidemics. Data for this review were obtained from literature published between 1967 and 2016 in key medical databases, the official websites of various governmental organisations, international public health agencies, and regulatory bodies. Despite major developments in the field of EVD, there has been little progress in its specific therapy or prevention. Historically, individuals who recovered from EVD acted as a source of fresh frozen plasma (containing IgG) that has been used to treat other acutely ill patients, however this therapeutic modality has limitations due to the risk of transmission of blood-borne infections. With the use of advanced and efficient purification methods the incidence of unwanted side effects following immune serum therapy has currently been greatly reduced. Creation of a safe plasma pool that covers immunoglobulins against all strains of EVD is now a research priority. Recommendations on how future EVD outbreaks can be better managed have been discussed.

Correlates of vaccine-induced protective immunity against Ebola virus disease.

Ebola virus disease is a deadly infection which occurs in sporadic outbreaks. Several vaccine candidates have been developed. The most advanced candidate is the recombinant VSVΔG-ZEBOV-GP vaccine, in which the Vesicular Stomatitis Virus (VSV) envelope glycoprotein is replaced by the Zaire strain Ebola virus (ZEBOV) glycoprotein (GP). This vaccine demonstrated 100% protection in a ring vaccination trial performed in Guinea in 2015, was granted "Breakthrough Therapy Designation" by the FDA and PRIority Medicines (PRIME), and is currently (June 2018) used to support outbreak control in Democratic Republic of Congo. rVSVΔG-ZEBOV-GP elicits a strong and durable antibody response in most vaccinees. This sustained Ebola GP-specific antibody response correlates with an early activation of innate immunity, especially of monocytes and of type-I interferon induced genes. Despite significant progress in the characterization of vaccine-induced immunity, human correlates of protection against Ebolavirus infection have not yet been fully established. A systems biology approach, integrating clinical, immunological, transcriptomic and metabolomic data from pre-clinical and clinical vaccine studies, together with data from disease survivors, will be instrumental to identify Ebola vaccine correlates of protection. The information generated for the rVSVΔG-ZEBOV-GP vaccine may also help identify the correlates of protection of the other Ebola vaccine candidates.

Epidemiology of ebolavirus disease (EVD) and occupational EVD in health care workers in Sub-Saharan Africa: Need for strengthened public health preparedness.

Ebolavirus disease (EVD) is a severe contagious disease in humans, and health care workers (HCW) are at risk of infection when caring for EVD patients. This paper highlights the epidemiologic profile of EVD and its impact on the health care workforce in Africa. A documentary study was conducted which consisted of a review of available literature regarding the epidemiology of EVD, occupational EVD (OEVD), and work safety issues in Sub-Saharan Africa; the literature findings are enriched by field experiences from the authors. EVD outbreaks have already caused 30,500 cases in humans of whom 12,933 died (as of September 9, 2015), and the number of infected HCW has dramatically increased. All eight HCW infected during the 2014 outbreak in Democratic Republic of the Congo died, whereas during the recent West African EVD epidemic more than 890 HCW were infected, with a case fatality rate of 57%. Occupational exposure to blood and other body fluids due to inadequate use of personal protective equipment and needle stick or sharp injuries are among factors that contribute to the occurrence of OEVD. Prevention of OEVD should be one of the top priorities in EVD outbreak preparedness and management, and research should be conducted to elucidate occupational and other factors that expose HCW to EVD. In addition to regularly training HCW to be adequately prepared to care for patients with EVD, it is critical to strengthen the general health care system and improve occupational safety in medical settings of countries at risk.

Monoclonal antibodies for the treatment of Ebola virus disease.

INTRODUCTION: To date, the management of patients with suspected or confirmed Ebolavirus disease (EVD) depends on quarantine, symptomatic management and supportive care, as there are no approved vaccines or treatments available for human use. However, accelerated by the recent large outbreak in West Africa, significant progress has been made towards vaccine development but also towards specific treatment with convalescent plasma and monoclonal antibodies. Areas covered: We describe recent developments in monoclonal antibody treatment for EVD, encompassing mAb114 and the MB-003, ZMAb, ZMapp™ and MIL-77E cocktails. Expert opinion: Preventive measures, are, and will remain essential to curb EVD outbreaks; even more so with vaccine development progressing. However, research for treatment options must not be neglected. Small-scale animal and individual human case studies show that monoclonal antibodies (mAbs) can be effective for EVD treatment; thus justifying exploration in clinical trials. Potential limitations are that high doses may be needed to yield clinical efficacy; epitope mutations might reduce efficacy; and constant evolution of (outbreak-specific) mAb mixtures might be required. Interim advice based on the clinical experience to date is that treatment of patients with mAbs is sensible, provided those could be made available in the necessary amounts in time.

Post-Ebolavirus disease syndrome: what do we know?

As the current Zaire ebolavirus disease outbreak in West Africa fades, the health problems of the more than 16,500 survivors have come to light. A wide range of mental and physical symptoms may occur during the convalescence stage. Reported symptoms of "post-Ebolavirus disease syndrome" (PEVDS) include chronic joint and muscle pain, fatigue, anorexia, hearing loss, blurred vision, headache, sleep disturbances, low mood and short-term memory problems. PEVDS has been associated with a decrease in functionality and difficulties to return to work. Further studies are needed to fully categorize the clinical spectrum of PEVDS. Diagnostic criteria and surrogate markers for the early diagnosis of PEVDS, and implementation of specialized health services to treat and follow-up survivors are also needed.

Post-Ebolavirus disease syndrome: What do we know?

As the current Zaire ebolavirus disease outbreak in West Africa fades, the health problems of the more than 16,500 survivors have come to light. A wide range of mental and physical symptoms may occur during the convalescence stage. Reported symptoms of "post-Ebolavirus disease syndrome" (PEVDS) include chronic joint and muscle pain, fatigue, anorexia, hearing loss, blurred vision, headache, sleep disturbances, low mood and short-term memory problems. PEVDS has been associated with a decrease in functionality and difficulties to return to work. Further studies are needed to fully categorize the clinical spectrum of PEVDS. Diagnostic criteria and surrogate markers for the early diagnosis of PEVDS, and implementation of specialized health services to treat and follow-up survivors are also needed.

Global lessons from Nigeria's ebolavirus control strategy.

The current Ebola virus disease outbreak challenged medical and public health systems in West Africa. In Nigeria, the existing infrastructure of the polio surveillance system was leveraged rapidly to contain the spread of Ebola virus. We highlight important lessons learnt from the successful implementation of Ebola virus disease surveillance strategies, which should be amplified further to prepare the ground for successful vaccination programs. Close collaboration between national and international stakeholders as well as public/private partnerships will be instrumental in future Ebola virus immunization strategies.