Outbreak In West Africa Research Articles

Evaluating crisis response speed of international organisations: why it matters and how to achieve it

ABSTRACT Armed conflicts, pandemics or natural disasters often necessitate rapid, coordinated responses by international organisations (IOs) to avoid escalation or loss of life. However, effective analytical tools to assess and compare the speed of these responses are lacking. This paper introduces a framework for evaluating IO crisis response speed, with the aim of better understanding which IOs are best equipped to offer rapid crisis responses and which are not. I propose a three-stage model that measures the time for IOs to (a) recognise a crisis, (b) decide on measures and (c) implement these measures, while also accounting for variations in levels of precision and obligation. Using empirical insights from the 2014 Ebola outbreak in West Africa, I demonstrate how this model can generate data that can improve our understanding of the performance of IOs as crisis managers and foster discussions on enhancing the speed and efficiency of multilateral responses during crises.

Designs for Vaccine Studies

Due to dependent happenings, vaccines can have different effects in populations. In addition to direct protective effects in the vaccinated, vaccination in a population can have indirect effects in the unvaccinated individuals. Vaccination can also reduce person-to-person transmission to vaccinated individuals or from vaccinated individuals compared with unvaccinated individuals. Design of vaccine studies has a history extending back over a century. Emerging infectious diseases, such as the SARS-CoV-2 pandemic and the Ebola outbreak in West Africa, have stimulated new interest in vaccine studies. We focus on some recent developments, such as target trial emulation, test-negative design, and regression discontinuity design. Methods for evaluating durability of vaccine effects were developed in the context of both blinded and unblinded placebo crossover studies. The case-ascertained design is used to assess the transmission effects of vaccines. The novel ring vaccination trial design was first used in the Ebola outbreak in West Africa.

Lassa virus persistence with high viral titers following experimental infection in its natural reservoir host, Mastomys natalensis

Lassa virus (LASV) outbreaks in West Africa pose a significant public health threat. We investigated the infection phenotype and transmission (horizontal and vertical) of LASV strain Ba366 in its natural host, Mastomys natalensis. Here we analyze viral RNA levels in body fluids, virus titers in organs and antibody presence in blood. In adults and 2-week-old animals, LASV causes transient infections with subsequent seroconversion. However, mice younger than two weeks exhibit persistent infections lasting up to 16 months despite antibody presence. LASV can be detected in various body fluids, organs, and cell types, primarily in lung, kidney, and gonadal epithelial cells. Despite the systemic virus presence, no pathological alterations in organs are observed. Infected animals efficiently transmit the virus throughout their lives. Our findings underscore the crucial role of persistently infected individuals, particularly infected females and their progeny, in LASV dissemination within the host population.

Clinical Management of Hospitalized Patients With High-Consequence Infectious Diseases in England.

Infectious disease physicians in England have been diagnosing and managing occasional cases of viral hemorrhagic fever since 1971, including the United Kingdom's first case of Ebola virus disease in 1976. Specialist isolation facilities to provide safe and effective care have been present since that time. Following the emergence of Middle East respiratory syndrome (MERS) in 2012, and the avian influenza A (H7N9) outbreak in 2013, and the 2014-2016 Ebola virus disease outbreak in West Africa, clinical and public health preparedness and response pathways in England have been strengthened for these types of diseases, now called high-consequence infectious diseases (HCIDs). The HCID program, led by NHS England and Public Health England between 2016 and 2018, helped to deliver these enhancements, which have since been used on multiple occasions for new UK cases and outbreaks of MERS, mpox, avian influenza, and Lassa fever. Additionally, HCID pathways were activated for COVID-19 during the first 3 months of 2020, before the pandemic had been declared and little was known about COVID-19 but HCID status had been assigned temporarily to COVID-19 as a precaution. The HCID program also led to the commissioning of a network of new airborne HCID treatment centers in England, to supplement the existing network of contact HCID treatment centers, which includes the United Kingdom's only 2 high-level isolation units. In this case study, the authors describe the airborne and contact HCID treatment center networks in England, including their formation and structures, their approach to safe and effective clinical management of patients with HCIDs in the United Kingdom, and challenges they may face going forward.

Genome-wide CRISPR/Cas9 screen identifies SLC39A9 and PIK3C3 as crucial entry factors for Ebola virus infection.

The Ebola virus (EBOV) has emerged as a significant global health concern, notably during the 2013-2016 outbreak in West Africa. Despite the clinical approval of two EBOV antibody drugs, there is an urgent need for more diverse and effective antiviral drugs, along with comprehensive understanding of viral-host interactions. In this study, we harnessed a biologically contained EBOVΔVP30-EGFP cell culture model which could recapitulate the entire viral life cycle, to conduct a genome-wide CRISPR/Cas9 screen. Through this, we identified PIK3C3 (phosphatidylinositide 3-kinase) and SLC39A9 (zinc transporter) as crucial host factors for EBOV infection. Genetic depletion of SLC39A9 and PIK3C3 lead to reduction of EBOV entry, but not impact viral genome replication, suggesting that SLC39A9 and PIK3C3 act as entry factors, facilitating viral entry into host cells. Moreover, PIK3C3 kinase activity is indispensable for the internalization of EBOV virions, presumably through the regulation of endocytic and autophagic membrane traffic, which has been previously recognized as essential for EBOV internalization. Notably, our study demonstrated that PIK3C3 kinase inhibitor could effectively block EBOV infection, underscoring PIK3C3 as a promising drug target. Furthermore, biochemical analysis showed that recombinant SLC39A9 protein could directly bind viral GP protein, which further promotes the interaction of viral GP protein with cellular receptor NPC1. These findings suggests that SLC39A9 plays dual roles in EBOV entry. Initially, it serves as an attachment factor during the early entry phase by engaging with the viral GP protein. Subsequently, SLC39A9 functions an adaptor protein, facilitating the interaction between virions and the NPC1 receptor during the late entry phase, prior to cathepsin cleavage on the viral GP. In summary, this study offers novel insights into virus-host interactions, contributing valuable information for the development of new therapies against EBOV infection.

“Bats Who Harm” and “Bats Who May Be Harmed”: The Interspecies Politics of Virus Sampling

Abstract The 2013–2016 Ebola virus outbreak in West Africa galvanized a quest for more knowledge with regards to the ecology of the disease. In its immediate aftermath, research initiatives, at the junction of biosecurity and One Health, were mounted to elucidate the circulation of the Ebola virus and other emergent pathogens through sampling local wildlife, in particular bats. The article investigates the knowledge, affects, and practices mitigating care and risk in encounters between human animals and potentially contaminated nonhuman animals. Grounded in an ethnography of the labor of wildlife sampling by Guinean veterinarians, it adopts an interspecies perspective on the One Health laboratory, a place where relations between animals and humans are inflected by a postcolonial, gendered, and anthropocentric imbalance of power. It argues that, rather than blurring interspecies boundaries, scientific care for sampled bats may cement hierarchies, with consequences for samplers and animals.

Understanding the Transmission Dynamics of the Chikungunya Virus in Africa.

The Chikungunya virus (CHIKV) poses a significant global public health concern, especially in Africa. Since its first isolation in Tanzania in 1953, CHIKV has caused recurrent outbreaks, challenging healthcare systems in low-resource settings. Recent outbreaks in Africa highlight the dynamic nature of CHIKV transmission and the challenges of underreporting and underdiagnosis. Here, we review the literature and analyse publicly available cases, outbreaks, and genomic data, providing insights into the epidemiology, genetic diversity, and transmission dynamics of CHIKV in Africa. Our analyses reveal the circulation of geographically distinct CHIKV genotypes, with certain regions experiencing a disproportionate burden of disease. Phylogenetic analysis of sporadic outbreaks in West Africa suggests repeated emergence of the virus through enzootic spillover, which is markedly different from inferred transmission dynamics in East Africa, where the virus is often introduced from Asian outbreaks, including the recent reintroduction of the Indian Ocean lineage from the Indian subcontinent to East Africa. Furthermore, there is limited evidence of viral movement between these two regions. Understanding the history and transmission dynamics of outbreaks is crucial for effective public health planning. Despite advances in surveillance and research, diagnostic and surveillance challenges persist. This review and secondary analysis highlight the importance of ongoing surveillance, research, and collaboration to mitigate the burden of CHIKV in Africa and improve public health outcomes.

Assignment of the Lassa virus transmembrane domain in the prefusion and postfusion states in detergent micelles.

Lassa virus (LASV) is the most prevalent member of the arenavirus family and the causative agent of Lassa fever, a viral hemorrhagic fever. Although there are annual outbreaks in West Africa, and recently isolated cases worldwide, there are no current therapeutics or vaccines. As such, LASV poses a significant global public health threat. One of the key steps in LASV infection is delivering its genetic material by fusing its viral membrane with the host cell membrane. This process is facilitated by significant conformational changes within glycoprotein 2 (GP2), yielding distinct prefusion and postfusion structural states. However, structural information is missing to understand the changes that occur in the transmembrane domain (TM) during the fusion process. Previously, we showed that the TM undergoes pH-dependent structural changes that result in a helical extension. Here, we provide the 1H, 15N, and 13C assignment of the LASV TM backbone in the prefusion and postfusion states. We also provide the 1H, 15N, and 13C assignment of two mutants, G429P and D432P, which prevent this helical extension. These results will help understand the role the TM plays in membrane fusion and can lead to the design of therapeutics against LASV infection.

Pollen metabarcoding reveals the origin and multigenerational migratory pathway of an intercontinental-scale butterfly outbreak

Migratory insects may move in large numbers, even surpassing migratory vertebrates in biomass. Long-distance migratory insects complete annual cycles through multiple generations, with each generation's reproductive success linked to the resources available at different breeding grounds. Climatic anomalies in these grounds are presumed to trigger rapid population outbreaks. Here, we infer the origin and track the multigenerational path of a remarkable outbreak of painted lady (Vanessa cardui) butterflies that took place at an intercontinental scale in Europe, the Middle East, and Africa from March 2019 to November 2019. Using metabarcoding, we identified pollen transported by 264 butterflies captured in 10 countries over 7months and modeled the distribution of the 398 plants detected. The analysis showed that swarms collected in Eastern Europe in early spring originated in Arabia and the Middle East, coinciding with a positive anomaly in vegetation growth in the region from November 2018 to April 2019. From there, the swarms advanced to Northern Europe during late spring, followed by an early reversal toward southwestern Europe in summer. The pollen-based evidence matched spatiotemporal abundance peaks revealed by citizen science, which also suggested an echo effect of the outbreak in West Africa during September-November. Our results show that population outbreaks in a part of species' migratory ranges may disseminate demographic effects across multiple generations in a wide geographic area. This study represents an unprecedented effort to track a continuous multigenerational insect migration on an intercontinental scale.

Rapid detection of Ebolavirus using isothermal recombinase-aided amplification.

Ebolavirus disease (EVD) is an often-lethal disease caused by the genus Ebolavirus (EBOV). Although vaccines are being developed and recently used, outbreak control still relies on a combination of various factors, including rapid identification of EVD cases. This allows rapid patient isolation and control measure implementation. Ebolavirus diagnosis is performed in treatment centers or reference laboratories, which usually takes a few hours to days to confirm the outbreak or deliver a clear result. A fast and field-deployable molecular detection method, such as the isothermal amplification recombinase-aided amplification (RAA), could significantly reduce sample-to-result time. In this study, a RT-RAA assay was evaluated for EBOV detection. Various primer and probe combinations were screened; analytical sensitivity and cross-specificity were tested. A total of 40 archived samples from the 2014 to 2016 Ebola outbreak in West Africa were tested with both the reference method real-time RT-PCR and the established RT-RAA assay. The assay could detect down to 22.6 molecular copies per microliter. No other pathogens were detected with the Ebolavirus RT-RAA assay. Testing 40 samples yield clinical sensitivity and specificity of 100% each. This rapid isothermal RT-RAA assay can replace the previous RT-RPA and continue to offer rapid EBOV diagnostics.

Research ethics preparedness during outbreaks and public health emergencies: Focus on community engagement

Research represents an essential component of the response to infectious disease outbreaks and to other public health emergencies, whether they are localised, of international concern, or global. Research conducted in such contexts also comes with particular ethics challenges, the awareness of which has significantly grown following the Ebola outbreak in West Africa, the Zika outbreak in Latin America and the COVID-19 pandemic. These challenges include the need for implementing meaningful community engagement with the researched communities, not just to build unidirectional trust towards the research team, but to achieve a genuine and mutually respectful partnership before, during and after the research. Here, we describe the real-life experience of 10 well-established research clinics in Nairobi, where a successful experience of community engagement linking prevention and care to research was interrupted during the COVID19 pandemic. We contrast this experience with the concept and processes of community engagement as described in selected scientific manuscripts and guidelines, to formulate some conclusions and recommendations. We contend that more action is needed, from research ethics committees and other key-research stakeholders, to align policies and practices with ethics guidance and with evidence-based recommendations from the academic literature, to achieve meaningful community engagement during emergency research, irrespective of the scale and location of an outbreak or public health crisis. Failure to do so, will aggravate the (postcolonial) asymmetries of power in global health and local systems.

Sosuga Virus Detected in Egyptian Rousette Bats (Rousettus aegyptiacus) in Sierra Leone.

Sosuga virus (SOSV), a rare human pathogenic paramyxovirus, was first discovered in 2012 when a person became ill after working in South Sudan and Uganda. During an ecological investigation, several species of bats were sampled and tested for SOSV RNA and only one species, the Egyptian rousette bat (ERBs; Rousettus aegyptiacus), tested positive. Since that time, multiple other species have been sampled and ERBs in Uganda have continued to be the only species of bat positive for SOSV infection. Subsequent studies of ERBs with SOSV demonstrated that ERBs are a competent host for SOSV and shed this infectious virus while exhibiting only minor infection-associated pathology. Following the 2014 Ebola outbreak in West Africa, surveillance efforts focused on discovering reservoirs for zoonotic pathogens resulted in the capture and testing of many bat species. Here, SOSV RNA was detected by qRT-PCR only in ERBs captured in the Moyamba District of Sierra Leone in the central region of the country. These findings represent a substantial range extension from East Africa to West Africa for SOSV, suggesting that this paramyxovirus may occur in ERB populations throughout its sub-Saharan African range.

Unraveling the effects of the Ebola experience on behavior choices during COVID-19 in Liberia: a mixed-methods study across successive outbreaks

BackgroundThe burden of the COVID-19 pandemic in terms of morbidity and mortality differentially affected populations. Between and within populations, behavior change was likewise heterogeneous. Factors influencing precautionary behavior adoption during COVID-19 have been associated with multidimensional aspects of risk perception; however, the influence of lived experiences during other recent outbreaks on behavior change during COVID-19 has been less studied.MethodsTo consider how the direct disease experience (“near misses”) and behavior change during the 2014–2016 Ebola virus disease (EVD) outbreak may have impacted behavior change during the early waves of the COVID-19 outbreak in West Africa, we analyzed data from a mixed-methods study that included a phone-based survey and in-depth interviews among vaccinated Liberian adults. Logistic regression via generalized estimating equations with quasi-likelihood information criterion (QIC)-based model selection was conducted to evaluate the influence of the interaction between and individual effects of the outbreak (EVD and COVID-19) and the “near-miss” experience on adoption of individual precautionary behaviors. Thematic analysis of interview transcripts explored reasons for differential behavior adoption between the two outbreaks.ResultsAt the population level, being a “near miss” was not associated with significantly different behavior during COVID-19 versus Ebola; however, overall, people had lower odds of adopting precautionary behaviors during COVID-19 relative to during Ebola. Participants who report near miss experiences during Ebola were significantly more likely to report having a household member test positive for COVID-19 (p<0.001). Qualitatively, participants often reflected on themes around more proximal and personal experiences with Ebola than with COVID-19; they also commented on how EVD led to better preparedness at the systems level and within communities for how to behave during an outbreak, despite such awareness not necessarily translating into action during COVID-19.ConclusionsThe results suggest that perceived proximity and intensity to disease threats in space and time affect behavioral decisions. For successive disease threats, comparisons of the present outbreak to past outbreaks compound those effects, regardless of whether individuals were directly impacted via a “near-miss” experience. Measures, such as risk communication and community engagement efforts, that gauge and reflect comparisons with previous outbreaks should be considered in response strategies to enhance the adoption of precautionary behavior.

Scalable gradients enable Hamiltonian Monte Carlo sampling for phylodynamic inference under episodic birth-death-sampling models.

Birth-death models play a key role in phylodynamic analysis for their interpretation in terms of key epidemiological parameters. In particular, models with piecewise-constant rates varying at different epochs in time, to which we refer as episodic birth-death-sampling (EBDS) models, are valuable for their reflection of changing transmission dynamics over time. A challenge, however, that persists with current time-varying model inference procedures is their lack of computational efficiency. This limitation hinders the full utilization of these models in large-scale phylodynamic analyses, especially when dealing with high-dimensional parameter vectors that exhibit strong correlations. We present here a linear-time algorithm to compute the gradient of the birth-death model sampling density with respect to all time-varying parameters, and we implement this algorithm within a gradient-based Hamiltonian Monte Carlo (HMC) sampler to alleviate the computational burden of conducting inference under a wide variety of structures of, as well as priors for, EBDS processes. We assess this approach using three different real world data examples, including the HIV epidemic in Odesa, Ukraine, seasonal influenza A/H3N2 virus dynamics in New York state, America, and Ebola outbreak in West Africa. HMC sampling exhibits a substantial efficiency boost, delivering a 10- to 200-fold increase in minimum effective sample size per unit-time, in comparison to a Metropolis-Hastings-based approach. Additionally, we show the robustness of our implementation in both allowing for flexible prior choices and in modeling the transmission dynamics of various pathogens by accurately capturing the changing trend of viral effective reproductive number.

Building Research Capacity in Low- and Middle-Income Countries and Pandemic Preparedness: Lessons Learned and Future Directions.

Research capacity is a critical component of pandemic preparedness, as highlighted by the challenges faced during the Ebola outbreak in West Africa. Recent global initiatives, such as the Research & Development Task Force of the Global Health Security Agenda and the World Health Assembly's resolution on strengthening clinical trials, emphasize the need for robust research capabilities. This Perspective discusses the experiences of leaders in infectious disease research and capacity building in low- and middle-income countries, focusing on Colombia, Jamaica, and Pakistan. These case studies underscore the importance of collaborative efforts, interdisciplinary training, and global partnerships in pandemic response. The experiences highlight the necessity for rapid pathogen identification, capacity for genomic sequencing, and proactive engagement with policymakers. Challenges faced, including the shortage of trained staff and reliance on imported reagents, emphasize the ongoing need for building research capacity.

Representations of an Ebola ‘outbreak’ through Story Technologies

BackgroundAttempts to understand biosocial phenomena using scientific methods are often presented as value-neutral and objective; however, when used to reduce the complexity of open systems such as epidemics, these forms...

Solusi Eksak Sistem Imun Terhadap Virus Ebola

The Ebola virus is a deadly disease that causes blood clots in the body's organs and is spread through direct contact with the blood or body fluids of sufferers. Based on this, the immune system in the body will continue to decrease and cause Ebola Hemorrhagic Fever. The 2014-2016 Ebola outbreak in West Africa has accelerated the development of several preventive vaccines against the Ebola virus. The goal of the vaccination is to induce immunity against infectious diseases. And also to stimulate the immune system and its ability to store and remember information about specific pathogens, leading to long-term protective immunity. The model equation for the Ebola virus vaccine in this study involves the concentration of the antigen which is a variable , by means of which the vaccine is inserted into the patient's body where it will attach to B memory cells which are variable , which will then be stimulated by the cells short-lived antibodies are denoted by variables or long-lived cells are denoted by variables , while antibodies will prove efficacy denoted by variables on the patient's immune response. The simulation of the exact solution for the Ebola vaccine uses the integration factor method which will later be compared with numerical simulations according to the parameter values from the research of Irene Balelli et al (2020). The simulation obtained has a very small calculation error value for each variable, which means that the exact value of the Ebola virus vaccination model shows that there is no significant difference to the numerical solution using the order 45 Rungge Kutta method, the largest resulting numerical error is 2.29640283510782×〖10〗^9.

RNA to Rule Them All: Critical Steps in Lassa Virus Ribonucleoparticle Assembly and Recruitment.

Lassa virus is a negative-strand RNA virus with only four structural proteins that causes periodic outbreaks in West Africa. The nucleoprotein (NP) encapsidates the viral genome, forming ribonucleoprotein complexes (RNPs) together with the viral RNA and the L protein. RNPs must be continuously restructured during viral genome replication and transcription. The Z protein is important for membrane recruitment of RNPs, viral particle assembly, and budding and has also been shown to interact with the L protein. However, the interaction of NP, viral RNA, and Z is poorly understood. Here, we characterize the interactions between Lassa virus NP, Z, and RNA using structural mass spectrometry. We identify the presence of RNA as the driver for the disassembly of ring-like NP trimers, a storage form, into monomers to subsequently form higher order RNA-bound NP assemblies. We locate the interaction site of Z and NP and demonstrate that while NP binds Z independently of the presence of RNA, this interaction is pH-dependent. These data improve our understanding of RNP assembly, recruitment, and release in Lassa virus.

Charting a healthier future: Africa CDC's strategic approach towards strengthening the health workforce of the African continent.

The health workforce plays a vital role in any healthcare system, underscored by the strong correlation between a higher density of skilled professionals and improved health outcomes. Notably, the COVID-19 pandemic, the 2014 Ebola outbreak in West Africa, and other disease emergencies have highlighted the acute shortage of health personnel in Africa. While progress has been made since 2013, but the global healthcare workforce deficit remained at 15 million in 2020, projected to decrease to 10 million by 2030 [...].

Sequence optimized diagnostic assay for Ebola virus detection

Rapid pathogen identification is a critical first step in patient isolation, treatment, and controlling an outbreak. Real-time PCR is a highly sensitive and specific approach commonly used for infectious disease diagnostics. However, mismatches in the primer or probe sequence and the target organism can cause decreased sensitivity, assay failure, and false negative results. Limited genomic sequences for rare pathogens such as Ebola virus (EBOV) can negatively impact assay performance due to undiscovered genetic diversity. We previously developed and validated several EBOV assays prior to the 2013–2016 EBOV outbreak in West Africa, and sequencing EBOV Makona identified sequence variants that could impact assay performance. Here, we assessed the impact sequence mismatches have on EBOV assay performance, finding one or two primer or probe mismatches resulted in a range of impact from minimal to almost two log sensitivity reduction. Redesigning this assay improved detection of all EBOV variants tested. Comparing the performance of the new assay with the previous assays across a panel of human EBOV samples confirmed increased assay sensitivity as reflected in decreased Cq values with detection of three positive that tested negative with the original assay.