Ebola-infected Patients Research Articles

Effective countermeasure for Filovirus infections: focusing monoclonal antibodies as passive prophylaxis shield against Ebola Virus disease.

In 2020 the pandemic of COVID 19 by SARS-COV 2 infected more than 27 million with more than 875,000 deaths. Present day world is more compact with quick mode of transport between far locations, this makes spread of new viral infections at alarming rates. Similarly, Filovirus is a family of extremely dangerous Marburgvirus and Ebolavirus with up to 90% mortality rate. Since first Filovirus was discovered in 1967, many outbreaks were reported from African countries. Increased number of infected human population in other outbreaks in 2014 – 2017 poses a question of our understanding of Filovirus reservoirs. We are beginning to understand the relation between virus and ecological agents and their role in the spread of disease, but it is still a long road ahead. To counteract and containment of Filovirus infection, it is utmost requirement to understand the viral life cycle patterns, agents involved and type of circulating strains in different geographical locations. This information will provide the basis to develop viable therapies to counteract future outbreaks. In these outbreaks’ magnitude of population and geographical area affected creates the urgency to generate effective vaccines and prophylactic agents so that mortalities can be controlled during future outbreaks. Therapies are required for pre-infection acute phase and post-infection. Here, we summarize recent advances in immunotherapy strategies that can be used as passive prophylaxis. We focused on development of recent monoclonal antibodies and cocktails that can be used as neutralizing agents or immunotherapy for Ebola infected patients During the pre-outbreak period it is required to vaccinate susceptible populations that will allow limiting the infection and mortalities. Furthermore, during the acute phase to neutralize virus and limiting disease symptoms, passive prophylaxis mean neutralizing antibodies are required. In the recent past few promising therapies are developed, some of these are on the clinical trial phase. Here we will review these therapies with their advantages in protecting against Filovirus.

The 500 years story of hydroxychloroquine and its implication on our medical knowledge: From Malaria to COVID-19

Quinine is a famous class of drugs over the last 500 years of the history of medicine. It does not treat disease symptoms, but rather modifies the underlying mechanism of the disproportionate effect of inflammation and immunity. Thus, it is described under the rubric of DMARD (Disease-Modifying Anti-Rheumatic Drugs). The mutation of SARS-CoV-1 to SARS-CoV-2  has given the virus the advantage  of bypassing many defenses, allowing the virus to spread widely, causing the current pandemic. During this progressive global crisis, the medical community began to repurpose many of the available drugs  to treat SARS-CoV-2  infection. Many antiviral drugs have been proposed. Using hydroxychloroquine   for the prevention and treatment of COVID-19 has received significant attention in 2020. The idea of using hydroxychloroquine came from previous experience during the initial outbreak of MERS in 2012 when physicians and other scientists conducted random observations on various approved medication to identify potential treatment for HIV, ZIKA virus-infected Ebola infected patients and MERS infection. Despite earlier encouraging findings from in vitro and early observational studies, randomised clinical trials showed the opposite. Thus, a need to reflect our interpretation of all the scientific findings at differ stages and settings.

Multi-professional simulation and risk perception of health care workers caring for Ebola-infected patients.

Treatment of infections that require high-level isolation can cause anxiety and fear among health care workers. Adequate and complete multi-professional simulation-based training could reduce those feelings and improve patient care. The purpose of this study was to assess the impact of multi-professional simulation-based training on the risk perception and preparedness of health care workers (registered nurses, doctors and ancillary staff) who care for patients assessed to be at risk or confirmed to have Ebola, level 3-4 biohazard. A prospective before-after study was designed. Health care workers who participated in a multi-professional simulation training course to improve the care of patients potentially infected with Level 3 and 4 biohazards were evaluated about their risk perception. The training was based on clinical scenarios. The evaluation was conducted using questionnaire based on Likert scale. After the training, a satisfaction survey about the most important aspects of the course was also conducted. Fifty-eight health care workers participated in the training course, 22 of whom were registered nurses. Participants presented positive changes after the training, increasing their sense of security, predisposition and confidence (p < 0.000001 for all). Multi-professional simulation-based training significantly improves the perception of safety and preparedness of health care workers regarding the care of patients potentially infected with Ebola virus and other Level 3-4 biohazards. The implementation of educational training strategies-such as simulations-is beneficial in improving the capacity of response and coping, as well as in reducing feelings of fear and insecurity.

Blood transfusion in sub-Saharan Africa: understanding the missing gap and responding to present and future challenges.

Blood transfusion in sub-Saharan Africa (SSA) is at a crossroad. Significant recent developments may help meet local needs in safe blood products and fulfil a global health target, as highlighted by the World Health Organization (WHO) Millennium and Sustainable Development Goals, in improving supply and safety, and ensuring the gradual implementation of selective haemotherapy. When WHO recommended the evaluation of convalescent blood or plasma to treat Ebola-infected patients during the recent epidemics, substantial gaps in local blood collection, testing and technology infrastructure and safety, as compared to best accepted quality standards, became evident. This evidence should now serve as an 'electro-shock'/awakening call used to highlight the needs for local governments to support National Blood Transfusion Services and establish robust national regulatory authorities that are mandated to bear regulatory responsibilities of blood establishments. A nationally co-ordinated blood programme is the best tool to gather reliable epidemiological data, address local needs in blood and blood products and serve public health. A literature review using WHO website and PubMed was conducted in this article to outline the current clinical use of blood products and plasma derivatives in SSA. This text also intends to highlight the gaps to be filled in the coming years with respect to quality, safety, supply and efficacy of blood and plasma products, in line with WHO guidelines for transfusion.

Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections.

BackgroundHuman Ebola infection is characterized by a paralysis of the immune system. A signature of αβ T cells in fatal Ebola infection has been recently proposed, while the involvement of innate immune cells in the protection/pathogenesis of Ebola infection is unknown. Aim of this study was to analyze γδ T and NK cells in patients from the Ebola outbreak of 2014–2015 occurred in West Africa, and to assess their association with the clinical outcome.Methodology/Principal findingsNineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Centre in Guinea. Patients were divided in two groups on the basis of the clinical outcome. The analysis was performed by using multiparametric flow cytometry established by the European Mobile Laboratory in the field. A low frequency of Vδ2 T-cells was observed during Ebola infection, independently from the clinical outcome. Moreover, Vδ2 T-cells from Ebola patients massively expressed CD95 apoptotic marker, suggesting the involvement of apoptotic mechanisms in Vδ2 T-cell loss. Interestingly, Vδ2 T-cells from survivors expressed an effector phenotype and presented a lower expression of the CTLA-4 exhaustion marker than fatalities, suggesting a role of effector Vδ2 T-cells in the protection. Furthermore, patients with fatal Ebola infection were characterized by a lower NK cell frequency than patients with non fatal infection. In particular, both CD56bright and CD56dim NK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56neg NK cells was associated to non-fatal infections. Finally, NK activation and expression of NKp46 and CD158a were independent from clinical outcome.Conclusions/SignificancesAltogether, the data suggest that both effector Vδ2 T-cells and NK cells may play a role in the complex network of protective response to EBOV infection. Further studies are required to characterize the protective effector functions of Vδ2 and NK cells.

Do ABO and Rhesus Blood Groups Affect Susceptibility to, and Prognosis of Ebola Virus Infection?

In 2014, the largest Ebola outbreak known to man, thundered through West Africa. It infected close to 30,000 people, and killed over 11,000. Yet, though we have known about Ebola for almost forty years, little data is available on survival and infection patterns of this viral hemorrhagic disease. Examining parallels between blood groups and human disease susceptibility is a valid, and increasingly used method of finding such patterns. This study permitted the observation of the different blood groups in Ebola infected patients and survivors. This was compared against the blood group distribution of the general population as well as those within the study, who succumbed to the disease. Blood group A in particular rose to 36.36% of the survivor population in our study, when it only forms 21.1% of the normal population. It formed 9% of the deceased group. The results show that the disparities in the blood group profiles of the general population, infected patients, survivors and deceased are marked enough to infer that ABO and Rhesus blood groups could be a factor in the infection and survival of Ebola Virus Disease (EVD)

Healthcare Professionals' Awareness, Knowledge, Attitudes, Perceptions and Beliefs about Ebola at Gondar University Hospital, Northwest Ethiopia: A Cross-sectional Study.

A poor understanding of Ebola Virus Disease (EVD) among Health Care Professionals (HCPs) may put our lives at risk. We aimed to assess the awareness, knowledge, attitudes, perceptions, beliefs of HCPs towards Ebola at Gondar University Hospital (GUH) in Northwest Ethiopia. We conducted a hospital based, cross-sectional survey among 245 randomly selected HCPs working at GUH from August-October, 2015. A validated, self-administered questionnaire was used to collect the data. We calculated descriptive statistics with P<0.05 being statistically significant. Of the 245 participants, 211 (86.1%) completed the study. The majority had heard about EVD and used news media (62%) as a source of information. Still, many were afraid of getting EVD (56.4%; P=0.001). A significant number of HCPs thought EVD can cause paralysis like polio (45%) and can be treated with antibiotics (28.4%). In addition, 46.4% of the HCPs felt anger or fear towards Ebola infected patients (P=0.006). We identified poor knowledge and negative incorrect beliefs among doctors and allied health professionals. There is a need for intensive training for all HCPs reduce EVD risk.

Ocular Complications in Survivors of the Ebola Outbreak in Guinea

The Ebola outbreak of 2013-2016 severely affected West Africa and resulted in 2544 deaths and 1270 survivors in Guinea, the country where it began. This Ebola virus was the Zaire strain of the virus family Filoviridae. In this outbreak the case fatality rate was about 67%. The survivors, declared cured after 2 negative blood polymerase chain reaction (PCR) results, face psychosocial disorders and rheumatic, ear-nose-throat, neurocognitive, and ophthalmologic complications. The goal of this study was to detect and describe ocular complications afflicting these survivors and to observe their occurrence and recurrences. Prospective observational cohort study. This prospective observational multicenter cohort study was initiated in March 2015. The cohort study included 341 survivors followed up in the infectious disease ward of Conakry, Forecariah, and Nzérékoré as of May 2016. The patients received multidisciplinary medical follow-up expected to last at least 1 year that included an eye examination as part of complete, free treatment. Systematic examination of 341 patients revealed 46 cases of uveitis (13.5%), 6 cases of episcleritis (1.8%), and 3 cases of interstitial keratitis (0.9%). Uveitis was most frequently unilateral (78.3%) and anterior (47.8%) and occurred within the 2months after discharge from the Ebola treatment center. Moreover, uveitis relapses were found up to 13months after the negative PCR result for Ebola in the blood. Nearly 1 out of 6 survivors presented ocular disorders after discharge from the Ebola treatment center. An ophthalmologic follow-up for Ebola-infected patients should start, if possible, during the acute phaseof the disease and last more than 1 year. Treatment guidelines need to be urgently developed and implemented.

IoT-based cloud framework to control Ebola virus outbreak.

Ebola is a deadly infectious virus that spreads very quickly through human-to-human transmission and sometimes death. The continuous detection and remote monitoring of infected patients are required in order to prevent the spread of Ebola virus disease (EVD). Healthcare services based on Internet of Things (IoT) and cloud computing technologies are emerging as a more effective and proactive solution which provides remote continuous monitoring of patients. A novel architecture based on Radio Frequency Identification Device (RFID), wearable sensor technology, and cloud computing infrastructure is proposed for the detection and monitoring of Ebola infected patients. The aim of this work is to prevent the spreading of the infection at the early stage of the outbreak. The J48 decision tree is used to evaluate the level of infection in a user depending on his symptoms. RFID is used to automatically sense the close proximity interactions (CPIs) between users. Temporal Network Analysis (TNA) is applied to describe and monitor the current state of the outbreak using the CPI data. The performance and accuracy of our proposed model are evaluated on Amazon EC2 cloud using synthetic data of two million users. Our proposed model provided 94 % accuracy for the classification and 92 % of the resource utilization.

Fear factor: The unseen perils of the Ebola outbreak

ABSTRACTAs illustrated powerfully by the 2013–2016 Ebola outbreak in western Africa, infectious diseases create fear and psychological reactions. Frequently, fear transforms into action – or inaction – and manifests as “fear-related behaviors” capable of amplifying the spread of disease, impeding life-saving medical care for Ebola-infected persons and patients with other serious medical conditions, increasing psychological distress and disorder, and exacerbating social problems. And as the case of the US micro-outbreak shows, fear of an infectious-disease threat can spread explosively even when an epidemic has little chance of materializing. Authorities must take these realities into account if they hope to reduce the deadly effects of fear during future outbreaks.

Proactive Risk Assessment for Ebola-Infected Patients: A Systematic Approach to Identifying and Minimizing Risk to Healthcare Personnel.

Performing patient care while wearing high-level personal protective equipment presents risks to healthcare providers. Our failure mode effects analysis identified 81 overall risks associated with providing hygienic care and linen change to a patient with continuous watery stool. Implementation of checklists and scheduled pauses could potentially mitigate 76.5% of all risks. Infect Control Hosp Epidemiol 2016;37:867-871.

Ethnomedical and ethnobotanical investigations on the response capacities of Guinean traditional health practioners in the management of outbreaks of infectious diseases: The case of the Ebola virus epidemic

Ethnopharmacological relevanceThe recent outbreak of Ebola virus infections has mostly remained confined to the West African countries Guinea-Conakry, Sierra-Leone and Liberia. Due to intense national and international mobilizations, a significant reduction in Ebola virus transmission has been recorded. While international efforts focus on new vaccines, medicines and diagnostics, no coherent national or international approach exists to integrate the potential of the traditional health practitioners (THPs) in the management of infectious diseases epidemics. Nevertheless, the first contact of most of the Ebola infected patients is with the THPs since the symptoms are similar to those of common traditionally treated diseases or symptoms such as malaria, hemorrhagic syndrome, typhoid or other gastrointestinal diseases, fever and vomiting. Materials and methodsIn an ethnomedical survey conducted in the 4 main Guinean regions contacts were established with a total of 113 THPs. The socio-demographic characteristics, the professional status and the traditional perception of Ebola Virus Disease (EVD) were recorded. ResultsThe traditional treatment of the main symptoms was based on 47 vegetal recipes which were focused on the treatment of diarrhea (22 recipes), fever (22 recipes), vomiting (2 recipes), external antiseptic (2 recipes), hemorrhagic syndrome (2 recipes), convulsion and dysentery (one recipe each). An ethnobotanical survey led to the collection of 54 plant species from which 44 identified belonging to 26 families. The most represented families were Euphorbiaceae, Caesalpiniaceae and Rubiaceae. Literature data on the twelve most cited plant species tends to corroborate their traditional use and to highlight their pharmacological potential. ConclusionsIt is worth to document all available knowledge on the traditional management of EVD-like symptoms in order to evaluate systematically the anti-Ebola potential of Guinean plant species.

Using the Untested Ebola Drug in Ebola Affected Patients: An Ethical Dilemma

The 2014 Ebola outbreak is the largest Ebola outbreak in history and the first in West Africa [1]. No specific vaccine or medicine (e.g., antiviral drug) has been proven to be effective against Ebola [2]. The standard treatment for Ebola remains supportive therapy [3]. ZMapp, being developed by Mapp Biopharmaceutical Inc., is an experimental treatment, for the use of the individuals infected with Ebola virus [3]. The product is a combination of three different monoclonal antibodies that bind to the protein of the Ebola virus [3]. The use of the drug for the Ebola infection presents a huge dilemma since it could have harmful side-effects and it has not yet been tested in humans for its effectiveness [3]. The Ebola infected patients might survive the Ebola infection but may die from side-effects of the drug ZMapp which are not yet known. ZMapp may cause side-effects which may not occur immediately and may be seen much later. Moreover, at this time very few courses of this experimental treatment have been manufactured [3] which raises issues on whom to use this drug if infected with the Ebola virus. Since, ZMapp is an experimental drug, patients may not agree to take this drug. This may be easy if the relationship between the patient and the health care provider is good. It will be interesting to study whether or not the Ebola infected patients who have received ZMapp develop any side-effects in future which could be related to this drug. The Ebola infection has posed a great challenge to the anti-microbial world and has raised many questions on the readiness of health care providers to contain this infection.

Tough challenges for testing Ebola therapeutics

At a briefing of United Nations officials on treating Ebola patients in western Africa with medicines and blood products in November last year, one question came up again and again: Why is it taking so long? Officials wanted to know why Ebola patients who have been evacuated to Europe or North America have had higher survival rates than those who remained in the outbreak countries, says scientist Martin Friede, who leads the technology transfer team at the World Health Organization (WHO) in Geneva. of these patients had received a whole range of drugs--everything and the kitchen sink--but I explained to them that we don't know what helped them to recover. Was it the clinical care? Was it the kitchen sink? he says. That's why we must do clinical trials to find out which drugs are safe and effective in these patients, says Friede, a former vice-president of development at California biotech company Apovia Inc., who joined WHO in 2003. Since WHO announced news of the Ebola outbreak in Guinea last March, the United Nations health agency has received more than 200 proposals of all kinds of therapies to treat Ebola virus disease suggestions. Some suggestions--such as ingesting vulture gastric juices and plant root extracts or wearing magnets--were rejected for their lack of scientific evidence. Others, including some drugs already licensed for other diseases, as well as novel drugs specifically aimed at Ebola that are under development, have been given to Ebola patients on compassionate grounds. far, however, there are no definitive data available to suggest that these interventions are either effective or safe in Ebola patients. Given the urgent need for additional therapies for Ebola--currently the only recommended management is replacement of fluids and electrolytes, and good control of symptoms--WHO is taking the lead in a major international drive to test potential therapies. Since August, the UN agency has organized a series of meetings of experts to review the pipeline of potential therapies for Ebola virus disease. As of 13 January, there were 21 373 cases and 8468 deaths in Guinea, Liberia and Sierra Leone, the three countries worst affected by the epidemic. Past Ebola outbreaks were often small, confined to one community, and halted quickly by detecting and isolating cases, identifying contacts and safely burying the deceased--reasons why drug development for Ebola stalled in the past. Clinical trials of potential therapies for Ebola can only be conducted during an outbreak, but there are enormous challenges with this. We identified only three products that work in the test tube and also give 100% protection in infected monkeys: ZMAPP (a cocktail of monoclonal antibodies), small inhibitory RNA, and anti-sense phosphorodiamidate morpholino oligomers, all targeting Ebola. [ILLUSTRATION OMITTED] But we don't know whether these are safe or effective in Ebola-infected patients and current supplies are nonexistent or limited to quantities that are sufficient only to conduct very small clinical trials, Friede says. So we drew up a short-list of repurposed drugs--i.e. ones developed for other conditions--including favipiravir, brincidofovir, toremefin and interferons, and we are continually reviewing this list as fresh data comes in on other drugs. With these repurposed drugs, there is less problem with supply, but a lack of clinical evidence of their effect against Ebola, Friede says, adding that testing these drugs in animals infected with Ebola is hampered by the fact that they must be done in participating biosafety-level 4 laboratories, of which there are only a handful in the world. Each of these facilities can only handle a small number of animals at a time. Favipiravir was developed by a Japanese company, Toyama Chemical, to treat influenza and some other viral infections and is being tested in Guinea for safety and efficacy in Ebola-infected humans by a team from the Institute of Health and Medical Research (INSERM) and Paris Diderot University in France. …

Ems and Ebola

This editorial questions the EMS readiness to deal with Ebola infected patients.