Search Results (18)

This paper studies the effects of resource limitations, immunity decay, and delays on an Ebola epidemic model and an optimal control strategy. The model includes two types of delays: a delay in the incubation period of infected individuals and a delay in treatment. Conditions for a Hopf bifurcation at the endemic equilibrium are verified, with its direction and stability analyzed via normal form theory and the center manifold theorem. We also studied the optimal control problem for the SIRD delay model using educational campaigns and Ebola survivors’ immunity as control variables. Furthermore, we formulate an optimization problem based on Pontryagin’s maximum principle. This problem uses a modified Runge-Kutta approach with delays to discover the best control strategy to reduce infections and intervention costs. Finally, simulation results confirm analytical conclusions and show the practical implications of the optimum Ebola control plan using the dde23 MATLAB R2024a built-in solver and DDE-Biftool. Full article

Ebola virus (EBOV) is one of three filovirus members of the Orthoebolavirus genus that can cause severe Ebola disease (EBOD) in humans. Transmission predominantly occurs from spillover events from wildlife but has also happened between humans with infected bodily fluids. Specifically, the sexual route through infectious male survivors could be the origin of flare up events leading to the deaths of multiple women. More studies are needed to comprehend this route of infection which has recently received more focus. The use of microbicides prior to intercourse is of interest if neither of the Ebola vaccines are an option. These experimental products have been used against sexually transmitted diseases, and recently polyphenylene carboxymethylene (PPCM) showed efficacy against EBOV in vitro. Shortly after, the first animal model of EBOV sexual transmission was established using type I interferon receptors (IFNAR^−/−) knockout female mice in which mortality endpoint could be achieved. Here, we investigated PPCM efficacy against a mouse-adapted (ma)EBOV isolate in IFNAR^−/− mice and demonstrated that 4% PPCM gel caused a 20% reduction in mortality in two distinct groups compared to control groups when inoculated prior to virus challenge. Among animals that succumbed to disease despite PPCM treatment, we report an increase in median survival time as well as a less infectious virus, and fewer virus positive vaginal swabs compared to those from vehicle-treated animals, altogether indicating the beneficial effect of using PPCM prior to exposure. A post-study analysis of the different gel formulations tested indicated that buffering the gels would have prevented an increase in acidity seen only in vehicles, suggesting that PPCM antiviral efficacy against EBOV was suboptimal in our experimental set-up. These results are encouraging and warrant further studies using optimized stable formulations with the goal of providing additional safe protective countermeasures from sexual transmission of EBOV in humans. Full article

Background: As the number of large-scale outbreaks continues to rise worldwide, clinical trials are increasingly engaging disease-affected peoples within the Minority World (nations with over 80% poverty rates). Yet global health research inadequately addresses potential ethical issues of including impoverished, disease-affected populations and their contextual vulnerabilities in medical research. Objective: This paper presents a mixed-method analysis from our 2022 semi-structured survey capturing the experiences of Liberian Ebola Virus Disease (EVD) survivors serving as study participants in the Partnership for Research on Ebola Virus in Liberia (PREVAIL) clinical trials. Methods: Firstly, we conducted an extensive literature review of the scholarship related to biomedical research and ethical standards protecting study participants to inform our survey method and design. Applying a theoretical framework on vulnerability, we then qualitatively explored the survey responses of 19 EVD survivors’ perceptions and experiences taking part in PREVAIL, including their expectations, treatment, delivered benefits, and quality of care. We further quantitatively codified their statements for underlying themes of reported negative experiences against standard ethical regulations in biomedical research, conducting a statistical analysis to inform generalizability. Most of the 19 survivors reported facing extreme ongoing vulnerabilities related to their disease status, including physical impairments, psychosocial stress, and socio-economic inequity. Results: Initially, the survivors tended to experience a sense of hope and pride in volunteering for PREVAIL. One in five participants reported benefiting from PREVAIL’s regular medical diagnoses. However, most of their survey responses indicated prevalent negative shared experiences, including continually being confused or misinformed of their study participant rights, roles, and benefits; being burdened by heavy participation transaction costs; and repeated incidents of poor treatment and discrimination by PREVAIL staff after initial recruitment. PREVAIL participant satisfaction ranking is negatively correlated with receiving insufficient financial compensation (r = −0.51), extensive time requirements for each medical visit (−0.40), and being poorly treated by clinical staff (−0.67). Full article

We sought to summarize knowledge, misconceptions, beliefs, and practices about Ebola that might impede the control of Ebola outbreaks in Africa. We searched Medline, EMBASE, CINAHL, and Google Scholar (through May 2019) for publications reporting on knowledge, attitudes, and practices (KAP) related to Ebola in Africa. In total, 14 of 433 articles were included. Knowledge was evaluated in all 14 articles, and they all highlighted that there are misconceptions and risk behaviors during an Ebola outbreak. Some communities believed that Ebola spreads through the air, mosquito bites, malice from foreign doctors, witchcraft, and houseflies. Because patients believe that Ebola was caused by witchcraft, they sought help from traditional healers. Some people believed that Ebola could be prevented by bathing with salt or hot water. Burial practices where people touch Ebola-infected corpses were common, especially among Muslims. Discriminatory attitudes towards Ebola survivors or their families were also prevalent. Some Ebola survivors were not accepted back in their communities; the possibility of being ostracized from their neighborhoods was high and Ebola survivors had to lead a difficult social life. Most communities affected by Ebola need more comprehensive knowledge on Ebola. Efforts are needed to address misconceptions and risk behaviors surrounding Ebola for future outbreak preparedness in Africa. Full article

Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone. Full article

Filoviruses, especially Ebola virus, cause sporadic outbreaks of viral haemorrhagic fever with very high case fatality rates in Africa. The 2013–2016 Ebola epidemic in West Africa provided large survivor cohorts spurring a large number of human studies which showed that specific neutralising antibodies played a key role in protection following a natural Ebola virus infection, as part of the overall humoral response and in conjunction with the cellular adaptive response. This review will discuss the studies in survivors and animal models which described protective neutralising antibody response. Their mechanisms of action will be detailed. Furthermore, the importance of neutralising antibodies in antibody-based therapeutics and in vaccine-induced responses will be explained, as well as the strategies to avoid immune escape from neutralising antibodies. Understanding the neutralising antibody response in the context of filoviruses is crucial to furthering our understanding of virus structure and function, in addition to improving current vaccines & antibody-based therapeutics. Full article

Recent Ebola epidemics, the ongoing COVID-19 pandemic, and emerging infectious disease threats have highlighted the importance of global infectious diseases and responses to public health emergencies. Ophthalmologists are essential health care workers who provide urgent and emergent vision care services during outbreaks and address the ocular consequences of epidemic and pandemic infectious diseases. In 2017, the World Health Organization (WHO) identified high priority pathogens likely to cause a future epidemic with the goal of guiding research and development to improve diagnostic tests, vaccines, and medicines. These measures were necessary to better inform and respond to public health emergencies. Given the ocular complications associated with emerging infectious diseases, there is a need to recognize the ophthalmic sequelae for future vision health preparedness for potential future outbreaks. The WHO High Priority pathogens list provides a roadmap for ophthalmologists and subspecialty providers that will guide strategic areas of research for clinical care and preparedness for future pandemic threats. This review summarizes these key viral pathogens, summarizes major systemic disease findings, and delineates relevant ocular complications of the WHO High Priority pathogens list, including Crimean-Congo hemorrhagic fever, Filovirus diseases (Ebola virus disease and Marburg hemorrhagic fever), human Coronaviruses, Lassa Fever, Nipah virus infection, Zika, and Rift Valley fever. Full article

The 2014–15 Ebola Virus Disease (EVD) outbreaks in Western Africa became widespread in primarily three countries, Guinea, Liberia, and Sierra Leone. Unlike all previous outbreaks in Central and East Africa, which were confined to rural areas, the virus spread rapidly through West Africa as a result of transmission through high-density urban centres coupled with the effects of public distrust in outbreak response teams and local government officials. Objective: In this study, we examine the EVD epidemic in Liberia, the first country to implement a community-based response that led to changes in the trajectory of the epidemic. The focus on the role of community-based initiatives in outbreak response is often neglected in conventional epidemiological accounts. In this light, we consider the manner in which community-based strategies enabled a more effective response based on the establishment of better trust relations and an enhanced understanding of the risks that EVD posed for the community. Methodology: We conducted qualitative research in five distinct communities in Liberia three years after the outbreaks subsided. Data collection procedures consisted of semi-structured interviews and focus group discussions with residents. Results: We found that the implementation of a community-based response, which included the participation of Ebola survivors and local leaders, helped curb and ultimately end the EVD epidemic in Liberia. As community members became more directly involved in the EVD response, the level of trust between citizens, local officials, and non-governmental organization response teams increased. In turn, this led to greater acceptance in abiding to safety protocols, greater receptiveness to risk information, and changes in mobility patterns—all of which played a significant role in turning the tide of the epidemic. Full article

The last seven years have seen the greatest surge of Ebola virus disease (EVD) cases in equatorial Africa, including the 2013–2016 epidemic in West Africa and the recent epidemics in the Democratic Republic of Congo (DRC). The vaccine clinical trials that took place in West Africa and the DRC, as well as follow-up studies in collaboration with EVD survivor communities, have for the first time allowed researchers to compare immune memory induced by natural infection and vaccination. These comparisons may be relevant to evaluate the putative effectiveness of vaccines and candidate medical countermeasures such as convalescent plasma transfer. In this study, we compared the long-term functionality of anti-EBOV glycoprotein (GP) antibodies from EVD survivors with that from volunteers who received the recombinant vesicular stomatitis virus vectored vaccine (rVSV-ZEBOV) during the Phase I clinical trial in Hamburg. Our study highlights important differences between EBOV vaccination and natural infection and provides a framework for comparison with other vaccine candidates. Full article

Ebola virus disease (EVD) and emerging infectious disease threats continue to threaten life, prosperity and global health security. To properly counteract EVD, an improved understanding of the long-term impact of recent EVD outbreaks in West Africa and the Democratic Republic of Congo are needed. In the wake of recent outbreaks, numerous health sequelae were identified in EVD survivors. These findings include joint pains, headaches, myalgias, and uveitis, a vision-threatening inflammatory condition of the eye. Retrospective and more recent prospective studies of EVD survivors from West Africa have demonstrated that uveitis may occur in 13–34% of patients with an increase in prevalence from baseline to 12-month follow-up. The clinical spectrum of disease ranges from mild, anterior uveitis to severe, sight-threatening panuveitis. Untreated inflammation may ultimately lead to secondary complications of cataract and posterior synechiae, with resultant vision impairment. The identification of Ebola virus persistence in immune privileged organs, such as the eye, with subsequent tissue inflammation and edema may lead to vision loss. Non-human primate models of EVD have demonstrated tissue localization to the eye including macrophage reservoirs within the vitreous matter. Moreover, in vitro models of Ebola virus have shown permissiveness in retinal pigment epithelial cells, potentially contributing to viral persistence. Broad perspectives from epidemiologic studies of the outbreak, animal modeling, and immunologic studies of EVD survivors have demonstrated the spectrum of the eye disease, tissue specificity of Ebola virus infection, and antigen-specific immunologic response. Further studies in these areas will elucidate the mechanisms of this highly prevalent disease with the potential for improved therapeutics for Ebola virus in immune-privileged sites. Full article

Background and objectives: In addition to conventional healthcare, Ebola survivors are known to seek traditional and complementary healthcare (T&CM) options to meet their healthcare needs. However, little is known about the general beliefs of Ebola survivors regarding T&CM and the impact of these beliefs in influencing their decisions around T&CM use. This study examines Ebola survivors’ attitudes towards T&CM use in Sierra Leone. Materials and Methods: We conducted a nationwide quantitative cross-sectional study of 358 Ebola survivors in Sierra Leone between January and August 2018. We used descriptive analysis, chi-square tests and backward stepwise binary logistic regression for data analysis. Results: Close to half of the survivors (n = 163, 45.5%) had used T&CM since their discharge from an Ebola treatment centre. Survivors who viewed T&CM as boosting their immune system/resistance were 3.89 times (95%CI: 1.57–9.63, p = 0.003) more likely to use T&CM than those who did not view T&CM as boosting their immune system/resistance. Additionally, survivors who viewed T&CM as having fewer side effects than conventional medicine were more likely to use T&CM [OR = 5.03 (95%CI: 1.92–13.19, p = 0.001)]. Ebola survivors were more influenced to use T&CM based on their personal experience of the effectiveness of T&CM than by clinical evidence [OR = 13.72 (95%CI: 6.10–30.84, P < 0.001)]. Ebola survivors who perceived T&CM as providing them with more control than conventional medicine over their health/body were more likely to use T&CM [OR = 4.15 (95%CI: 1.74–9.89, p = 0.001)] as opposed to those who did not perceive T&CM in this way. Conclusions: Considering the widespread use of T&CM, an understanding of Ebola survivors’ attitudes/beliefs towards T&CM is useful to healthcare providers and policymakers with regard to public education and practitioner–survivors communication, T&CM regulation and research in Sierra Leone. Ebola survivors appear to turn to T&CM not only for treatment, but also to fill gaps in conventional health care services. Full article

Ebola virus (EBOV) disease can result in a range of symptoms anywhere from virtually asymptomatic to severe hemorrhagic fever during acute infection. Additionally, spans of asymptomatic persistence in recovering survivors is possible, during which transmission of the virus may occur. In acute infection, substantial cytokine storm and bystander lymphocyte apoptosis take place, resulting in uncontrolled, systemic inflammation in affected individuals. Recently, studies have demonstrated the presence of EBOV proteins VP40, glycoprotein (GP), and nucleoprotein (NP) packaged into extracellular vesicles (EVs) during infection. EVs containing EBOV proteins have been shown to induce apoptosis in recipient immune cells, as well as contain pro-inflammatory cytokines. In this manuscript, we review the current field of knowledge on EBOV EVs including the mechanisms of their biogenesis, their cargo and their effects in recipient cells. Furthermore, we discuss some of the effects that may be induced by EBOV EVs that have not yet been characterized and highlight the remaining questions and future directions. Full article

Ebola virus (EBOV) infection is characterized by an excessive inflammatory response, a loss of lymphocytes and a general paralysis of the immune system, however pathophysiological mechanisms are not fully understood. In a cohort of 23 fatal and 21 survivors of ebola virus disease (EVD) cases admitted to the Emergency Ebola-Treatment-Center in Goderich (Freetown, Sierra Leone) during the 2014 to 2016 EBOV epidemic in Western Africa, we analyzed the pathway-focused gene expression profile of secreted proteins involved in the immune response and the levels of specific anti-EBOV IgM and IgG from the time of admission till discharge or death. We observed a dysregulated inflammatory response in fatal patients as compared to survivors, mainly consisting of the upregulation of inflammatory mediators, whose extent directly correlated with viremia levels. The upregulation persisted and intensified during the late phase of infection. Relevant differences were also found in humoral immunity, as an earlier and more robust EBOV antibody response was observed in survivor patients. Full article

Following the largest Ebola virus disease outbreak from 2013 to 2016, viral RNA has been detected in survivors from semen and breast milk long after disease recovery. However, as there have been few cases of sexual transmission, it is unclear whether every RNA positive fluid sample contains infectious virus. Virus isolation, typically using cell culture or animal models, can serve as a tool to determine the infectivity of patient samples. However, the sensitivity of these methods has not been assessed for the Ebola virus isolate, Makona. Described here is an efficiency comparison of Ebola virus Makona isolation using Vero E6, Huh-7, monocyte-derived macrophage cells, and suckling laboratory mice. Isolation sensitivity was similar in all methods tested. Laboratory mice and Huh-7 cells were less affected by toxicity from breast milk than Vero E6 and MDM cells. However, the advantages associated with isolation in Huh-7 cells over laboratory mice, including cost effectiveness, sample volume preservation, and a reduction in animal use, make Huh-7 cells the preferred substrate tested for Ebola virus Makona isolation. Full article

There is an increasing frequency of reports regarding the persistence of the Ebola virus (EBOV) in Ebola virus disease (EVD) survivors. During the 2014–2016 West African EVD epidemic, sporadic transmission events resulted in the initiation of new chains of human-to-human transmission. Multiple reports strongly suggest that these re-emergences were linked to persistent EBOV infections and included sexual transmission from EVD survivors. Asymptomatic infection and long-term viral persistence in EVD survivors could result in incidental introductions of the Ebola virus in new geographic regions and raise important national and local public health concerns. Alarmingly, although the persistence of filoviruses and their potential for sexual transmission have been documented since the emergence of such viruses in 1967, there is limited knowledge regarding the events that result in filovirus transmission to, and persistence within, the male reproductive tract. Asymptomatic infection and long-term viral persistence in male EVD survivors could lead to incidental transfer of EBOV to new geographic regions, thereby generating widespread outbreaks that constitute a significant threat to national and global public health. Here, we review filovirus testicular persistence and discuss the current state of knowledge regarding the rates of persistence in male survivors, and mechanisms underlying reproductive tract localization and sexual transmission. Full article