The outbreak of Ebola virus disease in 2022: A spotlight on a re-emerging global health menace

Ebola virus disease (EVD) is a rare but highly contagious and lethal disease that occurs predominantly in African countries, with a case-fatality rate of 30–90%. The causative viral pathogens of EVD are within the genus Ebolavirus in the family Filoviridae. The primary route of human-to-human transmission is through direct contact with blood, bodily fluids and secretions from infected individuals. Direct contact with virally contaminated objects and sexual transmission have also been reported. Management of EVD is aggressive supportive care with possibly new therapeutic options. On 20 September 2022, an EVD outbreak was declared in Uganda, caused by Sudan ebolavirus. As of 7 November 2022, a total of 136 confirmed cases, 53 confirmed deaths have been reported, including 18 cases with seven deaths among healthcare workers. In the Democratic Republic of Congo (DRC), an EVD outbreak was also declared on 22 August 2022 (which ended on 27 September 2022);with only one case, a middle-aged woman. At the time when most countries in the world have been occupied with the coronavirus disease 2019 (COVID-19) pandemic and the recent human monkeypox outbreak, these two outbreaks of EVD have the potential to significantly add to the burden on global health. Authorities need to augment their multi-faceted response, including stringent contact tracing and border control, to avoid the catastrophe of the 2014–2016 EVD epidemic. © 2022, School of Medicine, Universitas Syiah Kuala. All rights reserved.

Special Issue: Honor of Dr. Mike Bray on his retirement as the editor-in-chief of antiviral research. (Special Issue: Honor of Dr. Mike Bray on his retirement as the editor-in-chief of antiviral research.)

This special issue contains 23 articles that discuss various aspects of antiviral research, focusing on the contributions and legacy of Dr. Mike Bray, the retiring Editor-in-Chief of Antiviral Research. The articles cover a range of topics, including the underappreciated mouse model for Ebola virus disease, the history and impact of the mouse-adapted Ebola virus model, and the characterisation of CD-1 mice infected with different strains of Ebola virus. Other articles delve into transplacental vertical transmission of flaviviruses, the development of reverse genetic systems for SARS-CoV-2, and the mechanisms of action and drug resistance of nucleotide analogues against the virus. The special issue also explores therapeutics for flaviviral infections, alternative splicing in RNA virus infections, and targeted protein degradation as an antiviral approach.

Targeting virus-induced vulnerabilities using synthetic lethality as a new class of host-based antivirals

RNA viruses are the major class of human pathogens responsible for many global health crises, including the COVID-19 pandemic. However, the current repertoire of U.S. Food and Drug Administration (FDA)-approved antivirals is limited to only nine out of the known 214 human-infecting RNAviruses, and almost all these antivirals target viral proteins. Traditional antiviral development generally proceeds in a virus-centric fashion, and successful therapies tend to be only marginally effective as monotherapies, due to dose-limiting toxicity and the rapid emergence of drug resistance. Host-based antivirals have potential to alleviate these shortcomings, but do not typically discriminate between infected and uninfected cells, thus eliciting unintended effects. In infected cells where host proteins are repurposed by a virus, normal host protein functions are compromised;a situation analogous to a loss-of-function mutation, and cells harboring the hypomorph have unique vulnerabilities. As well-established in model systems and in cancer therapeutics, these uniquely vulnerable cells can be selectively killed by a drug that inhibits a functionally redundant protein. This is the foundation of synthetic lethality (SL). To test if viral induced vulnerabilities can be exploited for viral therapeutics, we selectively targeted synthetic lethal partners of GBF1, a Golgi membrane protein and a critical host factor for many RNA viruses including poliovirus, Coxsackievirus, Dengue, Hepatitis C and E virus, and Ebola virus. GBF1 becomes a hypomorph upon interaction with the poliovirus protein 3A. A genome-wide chemogenomic CRISPR screen identified synthetic lethal partners of GBF1 and revealed ARF1 as the top hit. Disruption of ARF1, selectively killed cells that synthesize poliovirus 3A alone or in the context of a poliovirus replicon. Combining 3A expression with sub-lethal amounts of GCA - a specific inhibitor of GBF1 further exacerbated the GBF1-ARF1 SL effect. Together our data demonstrate proof of concept for host-based SL targeting of viral infection. We are currently testing all druggable synthetic lethal partners of GBF1 from our chemogenomic CRISPR-screen, in the context of dengue virus infection for their abilities to selectively kill infected cells and inhibit viral replication and infection. Importantly, these SL gene partners of viral-induced hypomorphs only become essential in infected cells and in principle, targeting them will have minimal effects on uninfected cells. Our strategy to target SL interactions of the viral-induced hypomorph has the potential to change the current paradigm for host-based therapeutics that can lead to broad-spectrum antivirals and can be applied to other intracellular pathogens. This work is supported by National Institutes of Health grants R01 GM112108 and P41 GM109824, R21 AI151344 and foundation grant FDN-167277 from the Canadian Institutes of Health Research.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

"This Is Where We Have Scored”: Exploring the Interface between Project and Institutional Sustainability Facilitated by a Faith-Based Development Organisation in Sierra Leone

This paper explores the issue of project sustainability through an analysis of the experiences of a Faith-Based Development Organisation (FBDO) in Bo, Sierra Leone. The FBDO in question was approached by members of their local Catholic Women Association (CWA) to help them with the planning and management of a farm that had been donated to them by a chief. They agreed to this, and a series of workshops were held in June 2014, along with follow-up discussions with local experts and businesses as to what could be done to help support the women in their endeavour. Amongst other priorities, the women identified the need for the farm to produce food, income and help with their development. However, an outbreak of the Ebola virus that occurred between 2014 and 2016, following as it did on the back of an 11-year (1991–2002) civil war in Sierra Leone, led to a re-evaluation of the farm project in the eyes of the FBDO as they decided to shift to earlier priorities in education and health care. Given the constraints regarding resources and personnel, community projects, such as the CWA farm project, became of much lesser importance even though it resonated strongly with the goals of the FBDO and government, and had garnered much support amongst international donors. The paper sets out that story, beginning with the workshops and discussions held in 2014, and the ramifications of these responses to various ‘shocks', such as those presented by the civil war and disease outbreaks (Ebola and COVID-19);it also provides recommendations that might be of use regarding the interface between project and institutional sustainability within FBDOs and, indeed, the wider community of development organisations.

Convalescent plasma therapy for managing infectious diseases: A narrative review

The coronavirus disease 2019 (COVID-19) pandemic in 2020 is one of the worst catastrophic events in human history. A number of therapeutic modalities have been utilized in order to fight the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although the majority of them failed to demonstrate a beneficial clinical effect. Among the anti-COVID-19 agents being investigated, the convalescent plasma collected from recovered donors has gained a growing interest. Convalescent plasma has been employed for over a hundred years to treat severe acute viral infections when a vaccine or a specific antiviral treatment was not yet available. In this narrative review, we summarize the literature data on the use of convalescent plasma during previous viral outbreaks and pandemics, including influenza viruses, coronaviruses other than SARS-CoV-2 and Ebola virus. A literature search, using the Medline and PubMed electronic database, was performed to retrieve publications on the use of convalescent plasma in previous viral epidemics. In conclusion, the available literature data suggest the safety profile of convalescent plasma and its potential benefit in treating emerging viral infectious diseases. In addition, these data retrieved from previous viral epidemics provide a solid rationale for the employment of plasma from convalescent donors also in COVID-19 patients.Copyright © 2021 AME Publishing Company. All rights reserved.

COVID-19 and culture

The USA has been particularly hard hit by the COVID-19 pandemic and a wide spatial variation can be seen in its spread and mortality. This raises the question of why some regions are more resilient to the pandemic than others? We hypothesize that the individualism-collectivism cleavage explains the disparity in COVID-19 cases observed across sub-national units in the USA. Cultural disparity among different groups of people leads to differences in how they perceive health crises and thereby shapes the way they respond to pandemics. A heightened sense of obligation and responsibility increases in-group sociability and interdependence and raises the perceived vulnerability towards disease transmission among collectivistic individuals, and this leads to greater adherence to containment measures and social distancing rules. Our results provide evidence that more individualistic states tend to have more COVID-19 cases across the USA.

Preventive Measures against Ebola and COVID-19 and Their Impact on Human Dirty-Hand Disease Mitigation in Côte d'Ivoire

Hygiene is the most useful public health measure for preventing infections of important endemic and emerging diseases of global significance. This study aimed to assess the impact of these public health preventive measures on dirty hand diseases. A retrospective survey was conducted in the rural general hospitals of Taabo (south-central Côte d'Ivoire) and Marcory (urban Abidjan) to collect clinical data on dirty hand diseases in the patients' records from 2013 to 2020. In addition, focus group discussions (N = 8) were conducted in the communities in both settings to identify the sociocultural and economic hindering or fostering factors that affected the adoption of and the compliance with handwashing and disinfection practices. A total of 3245 and 8154 patients' records were examined in the general hospitals of Taabo and Marcory, respectively. Compared with women, men were more affected by typhoid fever (OR, 0.68 [95%CI, 0.53–0.88]) and influenza (OR, 0.87 [95%CI, 0.75–1]). Hygiene measures promoted during Ebola and COVID-19 outbreaks had no impact on the prevalence of typhoid fever in both settings;however, a positive impact was observed regarding influenza infections. Populations were aware of the importance of handwashing for public health but had difficulties adhering due to financial constraints, access to drinking water, and the absence or scarcity of handwashing facilities.

Current Advances in Novel SARS-CoV-2 Disease (COVID-19) Treatment and Intervention Strategies

Background: During the eleven months of the novel SARS-CoV-2 disease (COVID-19) outbreak in China and its global spread, there is a remarkable understanding of its epidemiology, pathobiol-ogy, and clinical management strategies. While countering a heavy toll on health and the economy, world's regional authorities are enforcing safety guidelines and providing patient care. Currently, there is no globally approved treatment or intervention for COVID-19. Method(s): A structured online literature search for peer-reviewed articles was conducted on PubMed, Europe PMC, Google, WHO, CDC, FDA, and ClinicalTrials portals, using phrases such as COVID-19 treatment and intervention, COVID-19 drugs and COVID-19 vaccines. Result(s): Analysis of the retrieved data showed that as a part of 'Solidarity Clinical Trials', hundreds of treatment and intervention strategies, including antiviral drugs, cytokine antagonists, convalescent plasma therapy, and vaccine candidates, have been registered worldwide. While remdesivir, the anti-Ebola virus drug, has been approved as an 'emergency use' drug in the USA, favipiravir, the anti-flu drug, has been recently approved in Russia. Tocilizumab and sarilumab, the cytokine (IL-6) antagonists, have entered Phase-II/III clinical trials in hospitalized COVID-19 patients. Among the leading vaccine candidates, Phase-III clinical trial results of Moderna, Pfizer and Oxford vaccines seem to be game changers for COVID19. Conclusion(s): The world health authorities have strongly and quickly responded to the COVID-19 pan-demic. Nonetheless, world bodies must unite in combating this health crisis by developing cost-effective drugs and vaccines and making them accessible to resource-poor countries.Copyright © 2021 Bentham Science Publishers.

Anthropogenic ecological changes and spill over of viruses - a review

Biodiversity protects ecosystem against infectious diseases. Increased human contact with wild life have caused high impact diseases such as SARS, Novel Corona virus, Nipah Virus, Ebola fever and many more. Anthropogenic activities such as hunting, farming, human encroachments, wild life trade, introduction of domestic species, bush meat hunting, road building, mining and increased human wildlife contact rates have lead to massive decline in biodiversity and increased risk of spilling over of dangerous viruses from animals to humans primarily due to host shifts. Human preference to high meat diet is also on rise in many countries. Wet markets have significant contribution in amplifying epizootic virus transmission and increased human exposure. Species in the primate and bat orders harbor a number of zoonotic viruses. Our destruction of nature, loss of habitat and biodiversity possibly tend to promote viral emergence. Invasion of undisturbed places leads to more and more exposure and create habitat where viral transmission is easier. Interference with a natural environment/habitat can, therefore, worsen the health risks. The erosion of biodiversity may lead to proliferation of species that are most likely to transmit new diseases to humans. Preserving habitat, biodiversity and natural environment is therefore one of the essential issues that cannot be put at the back any more.

Summary of global surveillance data of infectious diseases in December 2022

In December 2022, a total of 68 infectious diseases were reported globally, affecting 235 countries and regions. Except for influenza, the top five infectious diseases affecting greatest number of countries and regions were COVID-19 (235), monkeypox (110), dengue fever (28), measles (27) and cholera (14). The top five infectious diseases with highest case fatality rates were Ebola virus disease (47.0%), Rift Valley fever (44.2%), Crimean-Congo haemorrhagic fever (40.0%), Lassa fever (17.6%) and West Nile fever (7.6%). The top five infectious diseases with greatest number of deaths were COVID-19, malaria, cholera, dengue fever and measles. The prevalent infectious diseases in Asia were COVID-19, cholera and dengue fever, the prevalent infectious diseases in Africa were COVID-19, cholera, yellow fever, Lassa fever, monkeypox, malaria and measles, the prevalent infectious diseases in America were COVID-19, cholera, monkeypox, dengue fever and chikungunya fever, the prevalent infectious disease in Europe were COVID-19, monkeypox and invasive group A streptococcus infection.

Enveloped Viruses: Pathogenetic Targets for Cyanobacterial Lectins.

Lectins are a group of highly specific carbohydrate-binding proteins with a wide spectrum of action, involved in the so-called <<first line>> of body defense. These unique biomolecules show high specificity for various mono- and oligosaccharides, primarily for viral and bacterial glycoconjugates. Cyanobacteria lectins are effective against enveloped viruses and are an appealing alternative to existing synthetic drugs. Virtually complete absence of resistance formation in viruses to these compounds is known. The purpose of this review is to analyze, summarize, and discuss the results of experimental studies in vivo and in vitro, illustrating the mechanisms of action and antiviral effects of lectins obtained from cyanobacteria in relation to the most dangerous and socially significant viruses: SARS-Cov-2, HIV, Ebola viruses, influenza, and hepatitis C. In addition, the article outlines some of the challenges that must be overcome in order to obtain effective antiviral drugs in the future.Copyright © Team of Authors, 2022.

Enveloped Viruses: Pathogenetic Targets for Cyanobacterial Lectins.

Lectins are a group of highly specific carbohydrate-binding proteins with a wide spectrum of action, involved in the so-called <<first line>> of body defense. These unique biomolecules show high specificity for various mono- and oligosaccharides, primarily for viral and bacterial glycoconjugates. Cyanobacteria lectins are effective against enveloped viruses and are an appealing alternative to existing synthetic drugs. Virtually complete absence of resistance formation in viruses to these compounds is known. The purpose of this review is to analyze, summarize, and discuss the results of experimental studies in vivo and in vitro, illustrating the mechanisms of action and antiviral effects of lectins obtained from cyanobacteria in relation to the most dangerous and socially significant viruses: SARS-Cov-2, HIV, Ebola viruses, influenza, and hepatitis C. In addition, the article outlines some of the challenges that must be overcome in order to obtain effective antiviral drugs in the future.Copyright © Team of Authors, 2022.

Remdesivir (GS-5734) for COVID-19 Treatment: Past and Recent Updates

Background: SARS-CoV-2 is a pandemic now, and several measures have been taken by countries to prevent, control, and treat the disease. WHO has been working meticulously and has been providing up to date information and statistics on incidences and death. Several broad--spectrum anti-viral drugs are available and have been used in the past to fight against the viral out-break. Recently remdesivir, an experimental prodrug from Gilead Sciences, has been found to be a potential drug to be used as a therapy to treat COVID-19. Objective(s): Here, we have reviewed several previous findings from the literature and present an up to date information on remdesivir. Result(s): Remdesivir was initially invented for use against Ebola virus treatment and has proved ef-fective against different strains of Ebola, Nipah, and other strains of coronaviruses. Clinical trials with remdesivir for COVID-19 patients have begun, and several off label use of remdesivir have been reported recently. Currently, the drug seems to have an effect against the SARS-CoV-2 virus, with side effects among a few patients. Although the results are not conclusive, they are partly promising. This review provides past and recent updates on the use of remdesivir. Conclusion(s): From the review, we conclude that the drug remdesivir is known to exhibit its mechanism of action by terminating the RNA synthesis, and it is a potential drug against the novel coron-avirus.Copyright © 2021 Bentham Science Publishers.

Enhancing vaccination of key populations: lessons and actions

Vaccination is effective in preventing the increase of disease, especially emerging infectious diseases (EIDs), and it is particularly important for people in close contact with infected sources and susceptible populations who are at increased risk of getting infectious diseases due to behavior, occupation or health. Despite targeted vaccination guidelines, inadequate vaccination of the key populations fails to receive widespread attention, resulting in a high-risk transition of disease from key populations to general populations. Strengthening the vaccination of the susceptible groups can effectively block the spread of pathogens to general populations, and reduce the consumption of medical resources in universal vaccination, which has significant economic value. In this review, we describe the prevalence of EIDs, analyze the experience and lessons of infectious disease vaccination in key populations through several cases, and further explore the causes for the decline in vaccination rates of key populations. According to the trends of EIDs, a plan to strengthen the vaccination of key populations is proposed to effectively prevent the transition of EIDs from key populations to general populations.

Summary of national data of class A, B and C communicable diseases in China, December 2022

In December 2022 (from 00: 00, 1 December to 24: 00, 31 December), except COVID-19, a total of 278 907 cases of notifiable communicable diseases, including 2 384 deaths, were reported in China (except Hong Kong, Macao Special Administrative Regions and Taiwan Province, the same below). In communicable diseases in class A, no cases and no deaths were reported. In communicable diseases in class B, no cases and no deaths of severe acute respiratory syndrome, poliomyelitis, human infection with highly pathogenic avian influenza virus, diphtheria and human infection with avian influenza A (H7N9) virus were reported. For the remaining 21 communicable diseases except COVID-19 in class B, a total of 148 573 cases were reported, a decrease of 29% compared with last month (210 178 cases) and a decrease of 46% compared with the same period in 2021 (273 361 cases). The first 5 diseases in terms of reported case number were viral hepatitis, pulmonary tuberculosis, syphilis, gonorrhea and AIDS, accounting for 96% of the total reported cases in class B. A total of 2 384 deaths were reported, an increase of 28% (521 deaths) compared with last month (1 863 deaths) and a decrease of 14% compared with the same period in 2021 (2 763 deaths). In class C communicable diseases, a total of 130 334 cases were reported, a decrease of 33% compared with last month (195 072 cases) and a decrease of 69% compared with the same period in 2021 (420 015 cases). The first 3 diseases in terms of reported case number were influenza, other infectious diarrhea, and hand foot and mouth disease (HFMD), accounting for 96% of the total reported cases in class C. Compared with last month, except filariasis which had no incidence, the reported case number of leprosy was same, and the disease with reported case increase was echinococcosis (47 cases, 48%), the reported cases of other diseases all decreased, the first 3 diseases with reported case decreases were HFMD (22 886 cases, 45%), other infectious diarrhea (21 962 cases, 43%) and influenza (14 775 cases, 18%). Compared with the same period in 2021, except filariasis which had no incidence, the reported cases of other diseases all decreased, the first 3 diseases with reported case decreases were influenza (181 158 cases, 73%), other infectious diarrhea (53 502 cases, 65%) and HFMD (46 674 cases, 63%). No death caused by class C communicable disease was reported, same to last month and a decrease of 7 deaths compared with the same period in 2021 (7 deaths).

Enveloped Viruses: Pathogenetic Targets for Cyanobacterial Lectins

Lectins are a group of highly specific carbohydrate-binding proteins with a wide spectrum of action, involved in the so-called «first line» of body defense. These unique biomolecules show high specificity for various mono- and oligosaccharides, primarily for viral and bacterial glycoconjugates. Cyanobacteria lectins are effective against enveloped viruses and are an appealing alternative to existing synthetic drugs. Virtually complete absence of resistance formation in viruses to these compounds is known. The purpose of this review is to analyze, summarize, and discuss the results of experimental studies in vivo and in vitro, illustrating the mechanisms of action and antiviral effects of lectins obtained from cyanobacteria in relation to the most dangerous and socially significant viruses: SARS-Cov-2, HIV, Ebola viruses, influenza, and hepatitis C. In addition, the article outlines some of the challenges that must be overcome in order to obtain effective antiviral drugs in the future.

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.