Sudan Virus Research Articles

Crimean-Congo hemorrhagic fever cases diagnosed during an outbreak of Sudan virus disease in Uganda, 2022-23.

In September 2022, Uganda experienced an outbreak of Sudan virus disease (SVD), mainly in central Uganda. As a result of enhanced surveillance activities for Ebola disease, samples from several patients with suspected viral hemorrhagic fever (VHF) were sent to the VHF Program at Uganda Virus Research Institute (UVRI), Entebbe, Uganda, and identified with infections caused by other viral etiologies. Herein, we report the epidemiologic and laboratory findings of Crimean-Congo hemorrhagic fever (CCHF) cases that were detected during the SVD outbreak response. Whole blood samples from VHF suspected cases were tested for Sudan virus (SUDV) by real-time reverse transcription-polymerase chain reaction (RT-PCR); and if negative, were tested for CCHF virus (CCHFV) by RT-PCR. CCHFV genomic sequences generated by metagenomic next generation sequencing were analyzed to ascertain strain relationships. Between September 2022 and January 2023, a total of 2,626 samples were submitted for VHF testing at UVRI. Overall, 13 CCHF cases (including 7 deaths; case fatality rate of 53.8%), aged 4 to 60 years, were identified from 10 districts, including several districts affected by the SVD outbreak. Four cases were identified within the Ebola Treatment Unit (ETU) at Mubende Hospital. Most CCHF cases were males engaged in livestock farming or had exposure to wildlife (n = 8; 61.5%). Among confirmed cases, the most common clinical symptoms were hemorrhage (n = 12; 92.3%), fever (n = 11; 84.6%), anorexia (n = 10; 76.9%), fatigue (n = 9; 69.2%), abdominal pain (n = 9; 69.2%) and vomiting (n = 9; 69.2%). Sequencing analysis showed that the majority of identified CCHFV strains belonged to the Africa II clade previously identified in Uganda. Two samples, however, were identified with greater similarity to a CCHFV strain that was last reported in Uganda in 1958, suggesting possible reemergence. Identifying CCHFV from individuals initially suspected to be infected with SUDV emphasizes the need for comprehensive VHF testing during filovirus outbreak responses in VHF endemic countries. Without expanded testing, CCHFV-infected patients would have posed a risk to health care workers and others while receiving treatment after a negative filovirus diagnosis, thereby complicating response dynamics. Additionally, CCHFV-infected cases could acquire an Ebola infection while in the ETU, and upon release because of a negative Ebola virus result, have the potential to spread these infections in the community.

2022 Sudan Ebolavirus Outbreak in Uganda: Modelling Case Burden and Outbreak Duration.

In September 2022, an outbreak of Sudan virus (SUDV) was confirmed in Uganda. Following the first case report, we developed an individual based modelling platform (IBM-SUDV) to estimate the burden of cases and deaths, as well as the duration of the unfolding SUDV outbreak, using different scenarios. Modelled projections were within the range of cases and deaths ultimately observed.

The Role of Community Beliefs and Practices on the Spread of Ebola in Uganda, September 2022.

On September 20, 2022, Uganda declared an Sudan Virus Disease (SVD) outbreak in Mubende District. Another eight districts were infected September-November 2022. We examined how Ugandan community beliefs and practices spread Sudan Ebola Virus (SUDV) in 2022. A qualitative study was conducted in Mubende, Kassanda, and Kyegegwa districts in February 2023. Nine focus group discussions and six key informant interviews were held. We investigated whether community beliefs and practices contributed to spreading Sudan Ebola Virus (SUDV). Interviews were recorded, translated, transcribed, and thematically analyzed. The community deaths, later found to be due to Sudan Virus Disease(SVD), were often attributed to witchcraft or poisoning. Key informants reported that SVD patients often sought traditional healers or spiritual leaders before or after formal healthcare failed. They also found that traditional healers treated SVD patients without precautions. Religious leaders praying for SVD patients and their symptomatic contacts, SVD patients hiding in friends' homes, and exhuming SVD patients from safe and dignified burials to allow traditional burials were other themes. Diversity in community beliefs and culture likely contributed to spreading the 2022 Ugandan SVD outbreak. Public health systems, traditional healers, and religious leaders can help Uganda control ebolavirus outbreaks by identifying socially acceptable and scientifically supported infection control methods.

Immunogenicity of various variants of Ebola and Marburg virus glycoprotein genes in recombinant adenoviral vectors

INTRODUCTION. Marburg and Ebola viruses cause severe haemorrhagic fever in humans and primates. Currently, there are no licensed prophylactic vaccines that can simultaneously prevent the spread or reduce the severity of both diseases caused by these filoviruses. The development of effective prophylactic vaccines requires studies aimed at selecting the most immunogenic forms of protective antigens.AIM. This study aimed to evaluate humoral immune induction in animals after administration of recombinant adenoviral vectors expressing various forms of Ebola and Marburg virus glycoproteins (GPs).MATERIALS AND METHODS. Samples of recombinant human adenovirus type 5 (rAd5) were obtained using homologous recombination in Escherichia coli, growth in HEK293 cells, and purification by CsCl gradient ultracentrifugation. The resulting rAd5 samples were characterised in terms of their identity (PCR and whole-genome sequencing), the concentration of viral particles (fluorescence spectroscopy), and the concentration of infectious viral particles (TCID50 assay). Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the GP-specific IgG titres in the sera of immunised mice.RESULTS. The authors constructed rAd5 samples, and each construct contained an expression cassette with a GP gene form encoding a full-length GP, a GP without the mucin-like domain, or a GP without both the glycan cap and the mucin-like domain. Each of these forms was studied using the GPs of four filoviruses, including Zaire Ebola virus, Sudan Ebola virus, Bundibugyo Ebola virus, and Marburg virus. Neither of the forms had a critical effect on the rAd5 replicative capacity. Three weeks after immunisation, the highest GP-specific IgG production was induced by the rAd5 samples encoding either the full-length GP or the GP without the mucin-like domain. The GP without both the glycan cap and the mucin-like domain was the least immunogenic antigen regardless of the filovirus species.CONCLUSIONS. The most promising constructs for the development of filovirus vaccines based on recombinant adenoviral vectors are the constructs that include the genes encoding the fulllength GP or the GP without the mucin-like domain.

Feasibility Assessment of a Novel Isolation Care Tent in Uganda During the 2022 Sudan ebolavirus Outbreak.

This case study describes a feasibility assessment of a novel isolation care tent used in health facilities in Uganda during the 2022 Sudan ebolavirus outbreak. The Isolation System for Treatment and Agile Response to High-Risk Infections Model 1B (ISTARI 1B) is a single-occupancy, portable, negative-pressure isolation tent designed for the safe delivery of standard care to patients with a communicable disease, including Ebola disease (Sudan). At the request of the Uganda Ministry of Health, the Makerere University Infectious Diseases Institute and University of Nebraska Medical Center partnered to evaluate 7 health facilities across 4 districts in Uganda for infrastructure, case management, and infection prevention and control (IPC) capacity relevant to isolation care and ISTARI 1B use. A 3-day workshop was held with IPC leaders to provide familiarization and hands-on experience with the ISTARI 1B, delineate appropriate use scenarios in Ugandan healthcare settings, contextualize ISTARI 1B use in case management and IPC workflows, develop a framework for site assessment and implementation readiness, and consider ongoing monitoring, assessment, and intervention tools. Workshop participants performed a comprehensive site assessment and mock deployment of the ISTARI 1B. In this case study, we describe lessons learned from health facility assessments and workshop outcomes and offer recommendations to support successful ISTARI 1B implementation. Use scenarios and implementation strategies were identified across facility levels, including tools for site assessment, training, risk communication, and ongoing quality and safety monitoring.

A Virtual Assessment Model for At-Home Evaluation of Suspected Viral Hemorrhagic Fever Cases.

The Sudan virus disease outbreak in 2022 prompted the Denver Health High-Risk Infection Team (HITeam) to evaluate and implement novel strategies to respond to viral hemorrhagic fever (VHF) events. To improve the VHF response, HITeam members developed a virtual assessment model (VAM) for at-home evaluation of individuals who are suspected of having a VHF. The VAM incorporates aspects of care that would normally be rendered in a high-level isolation unit-including assessment and monitoring, specimen collection, provider consultation, patient and family teaching, and pharmaceutical intervention-into a mobile framework in which team members respond to a suspected case at the individual's home. Building this capability allows for more thorough assessment of a suspect case in the field, as well as the postponement of a decision about activation of the high-level isolation unit until more information is available. Development, testing, and implementation of the VAM required input from an interdisciplinary group of partners that demonstrated the ability of nurses, physicians, laboratorians, paramedics, emergency medical technicians, and public health personnel to integrate into 1 cohesive care team. The resulting model recenters VHF care on the patient by allowing the care team to gather critical information in an environment that is more comfortable for the suspect case while keeping communities safe and lowering exposure risks. The VAM has long-term sustainability implications for global VHF programs and provides solutions for broader challenges in healthcare by modeling cost-effective, patient-centered care within the highly nuanced subspecialty of special pathogen care.

Ebola disease outbreak caused by the Sudan virus in Uganda, 2022: a descriptive epidemiological study

Uganda has had seven Ebola disease outbreaks, between 2000 and 2022. On Sept 20, 2022, the Ministry of Health declared a Sudan virus disease outbreak in Mubende District, Central Uganda. We describe the epidemiological characteristics and transmission dynamics. For this descriptive study, cases were classified as suspected, probable, or confirmed using Ministry of Health case definitions. We investigated all reported cases to obtain data on case-patient demographics, exposures, and signs and symptoms, and identified transmission chains. We conducted a descriptive epidemiological study and also calculated basic reproduction number (Ro) estimates. Between Aug 8 and Nov 27, 2022, 164 cases (142 confirmed, 22 probable) were identified from nine (6%) of 146 districts. The median age was 29 years (IQR 20-38), 95 (58%) of 164 patients were male, and 77 (47%) patients died. Symptom onsets ranged from Aug 8 to Nov 27, 2022. The case fatality rate was highest in children younger than 10 years (17 [74%] of 23 patients). Fever (135 [84%] of 160 patients), vomiting (93 [58%] patients), weakness (89 [56%] patients), and diarrhoea (81 [51%] patients) were the most common symptoms; bleeding was uncommon (21 [13%] patients). Before outbreak identification, most case-patients (26 [60%] of 43 patients) sought care at private health facilities. The median incubation was 6 days (IQR 5-8), and median time from onset to death was 10 days (7-23). Most early cases represented health-care-associated transmission (43 [26%] of 164 patients); most later cases represented household transmission (109 [66%]). Overall Ro was 1·25. Despite delayed detection, the 2022 Sudan virus disease outbreak was rapidly controlled, possibly thanks to a low Ro. Children (aged <10 years) were at the highest risk of death, highlighting the need for targeted interventions to improve their outcomes during Ebola disease outbreaks. Initial care-seeking occurred at facilities outside the government system, showing a need to ensure that private and public facilities receive training to identify possible Ebola disease cases during an outbreak. Health-care-associated transmission in private health facilities drove the early outbreak, suggesting gaps in infection prevention and control. None.

N-Substituted Pyrrole-Based Heterocycles as Broad-Spectrum Filoviral Entry Inhibitors.

Since the largest and most fatal Ebola virus epidemic during 2014-2016, there have been several consecutive filoviral outbreaks in recent years, including those in 2021, 2022, and 2023. Ongoing outbreak prevalence and limited FDA-approved filoviral therapeutics emphasize the need for novel small molecule treatments. Here, we showcase the structure-activity relationship development of N-substituted pyrrole-based heterocycles and their potent, submicromolar entry inhibition against diverse filoviruses in a target-based pseudovirus assay. Inhibitor antiviral activity was validated using replication-competent Ebola, Sudan, and Marburg viruses. Mutational analysis was used to map the targeted region within the Ebola virus glycoprotein. Antiviral counter-screen and phospholipidosis assays were performed to demonstrate the reduced off-target activity of these filoviral entry inhibitors. Favorable antiviral potency, selectivity, and drug-like properties of the N-substituted pyrrole-based heterocycles support their potential as broad-spectrum antifiloviral treatments.

Understanding the delay in identifying Sudan Virus Disease: gaps in integrated disease surveillance and response and community-based surveillance to detect viral hemorrhagic fever outbreaks in Uganda, September 2022

BackgroundEarly detection of outbreaks requires robust surveillance and reporting at both community and health facility levels. Uganda implements Integrated Disease Surveillance and Response (IDSR) for priority diseases and uses the national District Health Information System (DHIS2) for reporting. However, investigations after the first case in the 2022 Uganda Sudan virus outbreak was confirmed on September 20, 2022 revealed many community deaths among persons with Ebola-like symptoms as far back as August. Most had sought care at private facilities. We explored possible gaps in surveillance that may have resulted in late detection of the Sudan virus disease (SVD) outbreak in Uganda.MethodsUsing a standardized tool, we evaluated core surveillance capacities at public and private health facilities at the hospital level and below in three sub-counties reporting the earliest SVD cases in the outbreak. Key informant interviews (KIIs) were conducted with 12 purposively-selected participants from the district local government. Focus group discussions (FGDs) were conducted with community members from six villages where early probable SVD cases were identified. KIIs and FGDs focused on experiences with SVD and Viral Hemorrhagic Fever (VHF) surveillance in the district. Thematic data analysis was used for qualitative data.ResultsForty-six (85%) of 54 health facilities surveyed were privately-owned, among which 42 (91%) did not report to DHIS2 and 39 (85%) had no health worker trained on IDSR; both metrics were 100% in the eight public facilities. Weak community-based surveillance, poor private facility engagement, low suspicion index for VHF among health workers, inability of facilities to analyze and utilize surveillance data, lack of knowledge about to whom to report, funding constraints for surveillance activities, lack of IDSR training, and lack of all-cause mortality surveillance were identified as gaps potentially contributing to delayed outbreak detection.ConclusionBoth systemic and knowledge-related gaps in IDSR surveillance in SVD-affected districts contributed to the delayed detection of the 2022 Uganda SVD outbreak. Targeted interventions to address these gaps in both public and private facilities across Uganda could help avert similar situations in the future.

Non-Ebola Filoviruses: Potential Threats to Global Health Security.

Filoviruses are negative-sense single-stranded RNA viruses often associated with severe and highly lethal hemorrhagic fever in humans and nonhuman primates, with case fatality rates as high as 90%. Of the known filoviruses, Ebola virus (EBOV), the prototype of the genus Orthoebolavirus, has been a major public health concern as it frequently causes outbreaks and was associated with an unprecedented outbreak in several Western African countries in 2013-2016, affecting 28,610 people, 11,308 of whom died. Thereafter, filovirus research mostly focused on EBOV, paying less attention to other equally deadly orthoebolaviruses (Sudan, Bundibugyo, and Taï Forest viruses) and orthomarburgviruses (Marburg and Ravn viruses). Some of these filoviruses have emerged in nonendemic areas, as exemplified by four Marburg disease outbreaks recorded in Guinea, Ghana, Tanzania, and Equatorial Guinea between 2021 and 2023. Similarly, the Sudan virus has reemerged in Uganda 10 years after the last recorded outbreak. Moreover, several novel bat-derived filoviruses have been discovered in the last 15 years (Lloviu virus, Bombali virus, Měnglà virus, and Dehong virus), most of which are poorly characterized but may display a wide host range. These novel viruses have the potential to cause outbreaks in humans. Several gaps are yet to be addressed regarding known and emerging filoviruses. These gaps include the virus ecology and pathogenicity, mechanisms of zoonotic transmission, host range and susceptibility, and the development of specific medical countermeasures. In this review, we summarize the current knowledge on non-Ebola filoviruses (Bombali virus, Bundibugyo virus, Reston virus, Sudan virus, Tai Forest virus, Marburg virus, Ravn virus, Lloviu virus, Měnglà virus, and Dehong virus) and suggest some strategies to accelerate specific countermeasure development.

The Importance of Networks and Relationships: Leveraging the Biocontainment Unit Leadership Workgroup for Special Pathogen Outbreak Response.

Developing and sustaining relationships and networks before an emergency occurs is crucial. The Biocontainment Unit Leadership Workgroup is a consortium of the 13 Regional Emerging Special Pathogen Treatment Centers in the United States. Established in 2017, the volunteer-based workgroup is composed of operational leaders dedicated to maintaining readiness for special pathogen care. Monthly meetings focus on addressing operational challenges, sharing best practices, and brainstorming solutions to common problems. Task forces are leveraged to tackle more complex issues that are identified as priorities. In 2022, members of the workgroup were harnessed for response efforts related to mpox, Sudan ebolavirus, and Marburg virus disease. The weekly Outbreak Readiness call is a shared effort between the Biocontainment Unit Leadership Workgroup and the Special Pathogens Research Network of the National Emerging Special Pathogens Training and Education Center. Call participants included leaders of the Regional Emerging Special Pathogen Treatment Centers and federal partners who shared weekly updates on operational readiness of units, case counts, laboratory capacity, available medical countermeasures, and other pertinent information. The routine exchange of real-time information enabled learning and collegial sharing of experiences, highlighted the experience of the network to federal partners, and provided situational awareness of special pathogen outbreaks across the country. The consortium enabled this rapid convening of partners to meet an urgent need for special pathogen response. The weekly Outbreak Readiness call is a communication model and scalable framework that serves both domestic preparedness efforts and international efforts should the need for a collaborative global response arise. In this case study, we describe the framework and experience of this partnership, along with the structure of rapid deployment for group convening.

Prevalence of and factors associated with anxiety, depression and post-traumatic stress disorder among Sudan ebolavirus disease survivors and family members, Uganda, January 2023: a cross-sectional study

BackgroundCommunities affected by Ebola disease (EBOD) may face resulting increases in mental health disorders. We evaluated the prevalence of and factors associated with mental health disorders among persons affected by the 2022 Sudan virus disease (SVD) outbreak in Uganda.MethodsWe conducted a cross-sectional study among SVD survivors and family members of survivors and fatal cases from 15–31 January 2023. We included only laboratory-confirmed SVD survivors and family members who lived with or cared for confirmed SVD patients during their illness. The Hospital Anxiety and Depression Scale was used to evaluate anxiety and depression. The post-traumatic stress disorder (PTSD) checklist for the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition was used to evaluate PTSD. Modified Poisson regression was used to determine factors associated with each mental health disorder.ResultsWe enrolled 54 survivors and 82 family members; median age was 30 years (range, 15–73) and 54% were female. The prevalence of anxiety (55%) and depression (50%) was higher than PTSD (17%). The prevalence of all mental health disorders was similar between survivors and family members. Household size was associated with both anxiety and PTSD. Number of SVD deaths in the household was associated with depression.ConclusionApproximately two-thirds of SVD survivors and family members of patients in the 2022 outbreak in Uganda had ≥ 1 mental health disorders shortly after the outbreak ended. Strengthening mental health services during and after Ebola virus outbreaks for survivors and family members of patients may enhance the quality of outbreak response.

Development of a Crystallographic Screening to Identify Sudan Virus VP40 Ligands.

The matrix protein VP40 of the highly pathogenic Sudan virus (genus Orthoebolavirus) is a multifunctional protein responsible for the recruitment of viral nucleocapsids to the plasma membrane and the budding of infectious virions. In addition to its role in assembly, VP40 also downregulates viral genome replication and transcription. VP40's existence in various homo-oligomeric states is presumed to underpin its diverse functional capabilities during the viral life cycle. Given the absence of licensed therapeutics targeting the Sudan virus, our study focused on inhibiting VP40 dimers, the structural precursors to critical higher-order oligomers, as a novel antiviral strategy. We have established a crystallographic screening pipeline for the identification of small-molecule fragments capable of binding to VP40. Dimeric VP40 of the Sudan virus was recombinantly expressed in bacteria, purified, crystallized, and soaked in a solution of 96 different preselected fragments. Salicylic acid was identified as a crystallographic hit with clear electron density in the pocket between the N- and the C-termini of the VP40 dimer. The binding interaction is predominantly coordinated by amino acid residues leucine 158 (L158) and arginine 214 (R214), which are key in stabilizing salicylic acid within the binding pocket. While salicylic acid displayed minimal impact on the functional aspects of VP40, we delved deeper into characterizing the druggability of the identified binding pocket. We analyzed the influence of residues L158 and R214 on the formation of virus-like particles and viral RNA synthesis. Site-directed mutagenesis of these residues to alanine markedly affected both VP40's budding activity and its effect on viral RNA synthesis, underscoring the potential of the salicylic acid binding pocket as a drug target. In summary, our findings lay the foundation for structure-guided drug design to provide lead compounds against Sudan virus VP40.

Delayed treatment of cynomolgus macaques with a FVM04/CA45 monoclonal antibody cocktail provides complete protection against lethal Sudan virus infection.

There are currently no approved vaccines or therapeutics for Sudan virus, a filovirus which is highly related to Ebola virus and causes similar disease and outbreaks. In this study, a cocktail of two potent monoclonal antibodies that effectively neutralize Sudan virus was tested in a nonhuman primate model of Sudan virus disease. Treatment was highly effective, even when initiated as late as 5 days after infection, when clinical signs of infection were already evident. All treated animals showed complete recovery from infection, with little evidence of disease, while all animals that received a control treatment succumbed to infection within 8 days. The study further demonstrated the strong therapeutic potential of the antibody treatment and supported further development for use in Sudan virus outbreaks.

Computational mining of B cell receptor repertoires reveals antigen-specific and convergent responses to Ebola vaccination.

Outbreaks of Ebolaviruses, such as Sudanvirus (SUDV) in Uganda in 2022, demonstrate that species other than the Zaire ebolavirus (EBOV), which is currently the sole virus represented in current licensed vaccines, remain a major threat to global health. There is a pressing need to develop effective pan-species vaccines and novel monoclonal antibody-based therapeutics for Ebolavirus disease. In response to recent outbreaks, the two dose, heterologous Ad26.ZEBOV/MVA-BN-Filo vaccine regimen was developed and was tested in a large phase II clinical trial (EBL2001) as part of the EBOVAC2 consortium. Here, we perform bulk sequencing of the variable heavy chain (VH) of B cell receptors (BCR) in forty participants from the EBL2001 trial in order to characterize the BCR repertoire in response to vaccination with Ad26.ZEBOV/MVA-BN-Filo. We develop a comprehensive database, EBOV-AbDab, of publicly available Ebolavirus-specific antibody sequences. We then use our database to predict the antigen-specific component of the vaccinee repertoires. Our results show striking convergence in VH germline gene usage across participants following the MVA-BN-Filo dose, and provide further evidence of the role of IGHV3-15 and IGHV3-13 antibodies in the B cell response to Ebolavirus glycoprotein. Furthermore, we found that previously described Ebola-specific mAb sequences present in EBOV-AbDab were sufficient to describe at least one of the ten most expanded BCR clonotypes in more than two thirds of our cohort of vaccinees following the boost, providing proof of principle for the utility of computational mining of immune repertoires.

Current updates on the epidemiology, pathogenesis and development of small molecule therapeutics for the treatment of Ebola virus infections

Ebola virus disease (EVD) is a rare, highly contagious and a deadly disease with a variable fatality rate ranging from 30% to 90%. Over the past two decades, Ebola pandemic has severely affected the sub-Sahara region including Democratic Republic of the Congo (DRC), and Uganda. The causative agents of the most EVD cases are three distinct species out of six Ebolaviruses namely Zaire Ebolavirus (ZEBOV), Sudan Ebolavirus (SUDV) and Bundibugyo Ebolavirus (BDBV). In recent years, significant strides have been made in therapeutic interventions. Notably, the US Food and Drug Administration has approved two monoclonal antibodies: InmazebTM (REGN-EB3) and Ansuvimab or Ebanga™. Additionally, many small molecules are currently in the developmental stage, promising further progress in medical treatment. Addressing the critical need for preventive measures, this review provides an in-depth analysis of the licensed Ebola vaccines-Ervebo and the combination of Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo) as well as the vaccines which are currently being tested for their efficacy and safety in clinical studies. These vaccines might play an important role in curbing the spread and mitigating the impact of this lethal disease. The current treatment landscape for EVD encompasses both nutritional (supportive) and drug therapies. The review comprehensively details the origin, pathogenesis, and epidemiology of EVD, shedding light on the ongoing efforts to combat this devastating disease. It explores small molecules in various stages of the development, discusses patents filed or granted, and delves into the clinical and supportive therapies that form the cornerstone of EVD management. This review aims to provide the recent developments made in the design and synthesis of small molecules for scientific community to facilitate a deeper understanding of the disease and fostering the development of effective strategies for prevention, treatment, and control of EVD.

Implementation of the WHO IPC Ring Approach During the 2022 Uganda Sudan Ebola Virus Disease (SUDV) Response at the Epicentre

Background: At the onset of an outbreak, immediate infection, prevention and control (IPC) measures and strategies are critically important in stopping the transmission. During the 2022 Sudan Virus Disease (SUDV) outbreak in Uganda, the IPC technical working group (TWG) adopted the WHO ring approach for intensive and targeted IPC support to interrupt transmission in high-risk areas and healthcare facilities (HCFs). Objectives: a) Leverage surveillance and epidemiological activities to guide response efforts and implement targeted IPC interventions. b) To rapidly interrupt SUDV transmission at the source through multiple IPC interventions. Methods: The IPC TWG delineated outbreak perimeters (rings) to include health facilities and community sites within 500 meters in urban centres and 1 kilometer in rural areas around each confirmed case. A data base with this information was developed and updated daily with information provided by the surveillance team. To activate response within 12 hours, interventions included rapid needs and risk assessments , health educational materials, deployment of decontamination teams and district IPC mentors with hygiene supplies delivered within 24 hours and a 72-hour follow-up. Trained Village Task Forces (VTF) and IPC mentors conducted health education, set up screening points, holding units, and rapid notification channels. Results: 56 rings including HCFs (38) and community sites (78) were identified within the radius of confirmed cases. Using the IPC scorecard, health facility mean scores significantly increased from 18% to 61.7% at follow-up in three weeks. Community WASH baseline scores improved from 11.1% (inadequate) to 69% with a basic level in two weeks. There was marked reduction in the incidence of new cases in the epicentre within the first 32 days. Conclusion: The results suggest that the IPC ring approach is an instrumental strategy health ministries can adopt to rapidly provide targeted comprehensive support at the source to interrupt transmission. A collaborative effort across pillars and partners in the implementation of the ring approach is key through concerted efforts and information sharing across response pillars.

Rapid Scale-Up of Screening for Early Detection of Sudan Virus Disease (SVD) in Healthcare Facilities (HCFs) during the 2022 Outbreak in Uganda

Background: The Uganda Ministry of Health (MoH) and implementing partners instituted an infection prevention and control (IPC) response strategy during the Uganda SVD outbreak in 2022 that involved rapid enhancement of screening capacity at HCFs. Rapid scale-up of screening for infectious diseases, such as SVD, is critical for early identification and triage of suspected or confirmed cases in HCFs. We describe the rapid deployment of a multimodal IPC strategy implemented in response to the SVD outbreak and the resulting impact on screening measures at HCFs. Methods: We implemented a multimodal IPC strategy in HCFs from five high risk districts to improve screening practices from November 2022–January 2023. The strategy included training health workers (HCWs) identified as IPC mentors; establishing screening areas; and providing screening supplies and communication materials. The three-day training utilized an MoH standardized training package with didactic and practice sessions. The mentors then cascaded screening information and skills to other HCWs through onsite trainings and mentorships and established screening areas. Baseline and endline (3 months after baseline) cross-sectional assessments were conducted using the MoH IPC Assessment Tool adapted from the WHO Ebola IPC Scorecard. The five main screening parameters assessed included presence of ≥ 1 meter distance between screener and the person screened, availability of a functional handwashing facility and infrared thermometer, correct record of each person’s temperature, and appropriate referral process for those suspected of having SVD to holding areas. IPC capacity was measured through the summation of each of these parameter results and calculated as an overall percentage. IBM SPSS Statistics 20 software was used for data analysis and a paired t-test done to determine any significant findings between mean scores (percentage) at baseline and endpoint. Results: A total of 296 IPC mentors were trained, screening information was cascaded to 3,899 HCWs, and screening areas were established in 1,135 HCFs. Based on the screening results from the MoH IPC assessment tool, capacity improved from 44% (SD=37) at baseline to 67% (SD=34) at endpoint. Screening capacity improved from baseline to endpoint among level II and public HCFs from 33% (SD=35) to 60% (SD=35) (p &lt; 0 .05) and from 54% (SD=38) to 76% (SD=31) (p &lt; 0 .05), respectively. Conclusion: Rapid implementation of a multimodal IPC strategy was successful in enhancing screening capacity across Uganda’s HCFs during a SVD response, which is critical for early identification of infected patients to interrupt transmission. This multimodal approach should be recommended for future response actions.

Molecular determinants of cross-species transmission in emerging viral infections.

SUMMARYSeveral examples of high-impact cross-species transmission of newly emerging or re-emerging bat-borne viruses, such as Sudan virus, Nipah virus, and severe acute respiratory syndrome coronavirus 2, have occurred in the past decades. Recent advancements in next-generation sequencing have strengthened ongoing efforts to catalog the global virome, in particular from the multitude of different bat species. However, functional characterization of these novel viruses and virus sequences is typically limited with regard to assessment of their cross-species potential. Our understanding of the intricate interplay between virus and host underlying successful cross-species transmission has focused on the basic mechanisms of entry and replication, as well as the importance of host innate immune responses. In this review, we discuss the various roles of the respective molecular mechanisms underlying cross-species transmission using different recent bat-borne viruses as examples. To delineate the crucial cellular and molecular steps underlying cross-species transmission, we propose a framework of overall characterization to improve our capacity to characterize viruses as benign, of interest, or of concern.

Ebola virus circulation in a non‐epidemic Guinean rural area: A mixed‐method approach to assessing endemicity

ObjectivesThis study aimed to investigate the prevalence of orthoebolavirus antibodies in Madina Oula, a non-epidemic rural area in Guinea, in 2022. MethodsA cross-sectional study was conducted from March 14 to April 3, 2022 involving recording household and socio-demographic characteristics, lifestyle data, and collecting dried blood spots from 878 individuals in 235 households. Dried blood spots were tested using multiplex serology to detect antibodies to different orthoebolaviruses: Ebola virus, Bundibugyo virus, Sudan virus, Reston virus, and Bombali virus. Seroprevalence was estimated with a 95% confidence interval and a Z-test was performed to compare the seropositivity between children aged under 15 years and those over 15 years. Household and participant characteristics were analyzed using descriptive statistic, and socio-historical conditions were discussed. ResultsThe serological analysis conducted in 2022 on 878 participants revealed varying reactivity to orthoebolavirus antigens, notably, with glycoprotein antigens, particularly, glycoprotein Sudan virus (16%). A total of 21 samples exhibited reactivity with at least two antigens, with a median age of 27 years (interquartile range 10.00-35.00), ranging from 2 to 80 years. There is no significant difference between seropositivity in children aged under 15 (2.86%) years and those over 15 (2.14%) years. The antibody presence varied per village, with the highest prevalence observed in Ouassou and Dar-es-Salam. ConclusionsSerological data in a region unaffected by recent Ebola outbreaks indicate possible orthoebolavirus endemicity, emphasizing the need for preparedness against known or novel orthoebolaviruses with potential cross-reactivity.