Outbreak Response Research Articles

The oral drug obeldesivir protects nonhuman primates against lethal Ebola virus infection.

Obeldesivir (ODV; GS-5245) is an orally administered ester prodrug of the parent nucleoside GS-441524 that has broad spectrum antiviral activity inhibiting viral RNA-dependent RNA polymerases. We recently showed that ODV completely protects cynomolgus macaques against lethal infection with Sudan virus when given 24 hours after parenteral exposure. Here, we report that once daily oral ODV treatment of cynomolgus and rhesus macaques for 10 days confers 80 and 100% protection, respectively, against lethal Ebola virus infection when treatment is initiated 24 hours after mucosal (conjunctival) exposure. ODV treatment delayed viral replication to abate excessive inflammation and promote adaptive immunity. For outbreak response, oral antivirals might present substantial advantages over now approved intravenous drugs, such as easy supply, storage, distribution, and administration. Furthermore, these results support the potential of ODV as an oral postexposure prophylaxis with broad spectrum activity across filoviruses.

Cholera in conflict: outbreak analysis and response lessons from Gadaref state, Sudan (2023–2024)

BackgroundCholera is an acute, severe, illness caused by infection with Vibrio cholerae. Cholera outbreaks are closely linked to armed conflicts and humanitarian emergencies. This study describes the cholera outbreak amidst conflict in Gadaref state, discusses the possible factors mediated its spread and proposes future improvements in preparedness and response measures.MethodsA retrospective analytical study was conducted using national surveillance records of cholera cases, supported by interviews with key informants involved in preparedness and response, along with a review of state reports, to identify possible factors contributing to the spread and to evaluate the response.ResultThe outbreak was confirmed after the isolation of Vibrio cholerae of O1 serotype, with both Inaba and Ogawa serogroups. A total of 2,047 cholera cases records reviewed. The mean age was 16.8 (SD, 15.8) with an equal gender distribution. The case fatality ratio was 2.4% and the overall attack (AR) rate was 7.38 cases per 10,000 population, with the highest in Medeinat Gadaref locality (21.07/10,000). Interviews and reports review suggest that the outbreak was likely imported to villages near Ethiopian border before spreading to other parts of Gadaref. Atbara seasonal river, was the identified source of infection at the beginning. A disrupted health system due to conflict, delays in response teams’ deployment, and late implementation of control measures were identified as factors contributing to response delay and expansion of the outbreak. Oral cholera vaccine campaign was implemented in five localities, followed by an observable decline in cases.ConclusionCholera remains a recurrent risk that has been further exacerbated by the armed conflict. The reporting of index cases from a border village highlights the need to strengthen surveillance at points of entry. Investment in case management and risk communication is necessary to improve clinical outcomes. The use of Oral Cholera Vaccine was associated with a decline in cases; however, further field studies are recommended to analyze its actual contribution in limiting the outbreak. The government’s primary role in leading and financing preparedness and response interventions has been limited by the conflict, urging investment in community-led interventions, while moving to more strategic outbreak preparedness and response financing mechanisms remains a priority, with partner support being essential in conflict settings.

Navigating the Road to Immunization Equity: Systematic Review of Challenges in Introducing New Vaccines into Sub-Saharan Africa’s Health Systems

Background/Objectives: Over the past 50 years, developing new vaccines has been pivotal in responding to emerging and re-emerging diseases globally. However, despite substantial partner support, introducing new vaccines in sub-Saharan Africa remains challenging. This systematic review documents the barriers to new vaccine introduction in sub-Saharan Africa by distinguishing between vaccines integrated into routine immunization programs and those introduced primarily for outbreak response. Methods: A comprehensive electronic search was conducted across five databases for articles published in English or French on the challenges of new vaccine introduction in sub-Saharan Africa. Three reviewers screened articles independently based on the titles and abstracts, with full-text assessments conducted for inclusion. Data were analyzed thematically and synthesized narratively. Results: A total of 796 articles were retrieved from the five databases. Following the screening, 33 articles were finally retained and included in the review. These articles concerned the introduction of eight new vaccines (malaria vaccine, COVID-19 vaccine, HPV vaccine, Ebola vaccine, cholera vaccine, hepatitis B vaccine, rotavirus vaccine, and typhoid vaccine). The analyses revealed coordination and financing challenges for six vaccines in seventeen countries, acceptability challenges for five vaccines in ten countries, logistical challenges for two vaccines in six countries, and quality service delivery challenges for three vaccines in thirteen countries. Conclusions: Addressing the challenges of introducing new vaccines in sub-Saharan Africa requires targeted, evidence-based strategies. Prioritizing political commitment, innovative funding, public education, workforce development, and infrastructure improvements will strengthen immunization systems and enable timely vaccine delivery. Collaborative efforts and a focus on local context can advance equitable health outcomes, safeguard public health, and support global immunization goals.

A One Health approach for South American hemorrhagic fevers

Abstract South American hemorrhagic fevers (SAHF) include five rodent-borne New World mammarenaviruses. These are Junin, Machupo, Chapare, Guanarito, and Sabia viruses. Their incidence is relatively low and limited to sporadic outbreaks in certain regions of Argentina, Brazil, Bolivia, and Venezuela. However, these hemorrhagic fevers have high mortality rates, a proven capacity for limited human-to-human spread and their spillover risk is potentially increasing with regional agricultural land-use change. Despite this, SAHF remain largely understudied. There is growing acknowledgment from global health experts of the epidemic potential of SAHF. In 2023, the Coalition for Epidemic Preparedness announced it is developing a novel Junin vaccine. In 2024, WHO included SAHF in its Pathogen Prioritization Report. However, there has been limited explicit discussion of SAHF from a One Health perspective. We believe adopting a comprehensive One Health approach for SAHF could enable the development of more effective surveillance and control strategies. We reviewed the key clinical and epidemiological characteristics of SAHF for One Health practitioners. Drawing from Machupo outbreak responses and One Health programs for Lassa Fever, we propose two One Health strategies for SAHF management. These are to enhance rodent surveillance programs and improve rodent control programs to limit spillovers and control outbreaks of SAHF. One Health impact statement There has been limited explicit discussion of SAHF from a One Health perspective. This is notable given the zoonotic nature of SAHF, their susceptibility to agricultural-land use change and their epidemic potential. Our commentary aims to inform One Health practitioners of the most pertinent clinical and epidemiological aspects of SAHF. We propose two transdisciplinary and collaborative One Health strategies focused on protecting human, animal, and environmental health. Ultimately, we hope to stimulate research into One Health approaches for SAHF.

Candida auris Outbreak and Epidemiologic Response in Burn Intensive Care Unit, Illinois, USA, 2021-2023.

Candida auris is an emerging fungal pathogen associated with outbreaks in healthcare settings. We report a multiyear outbreak of C. auris in a burn intensive care unit in Illinois, USA, during 2021-2023. We identified 28 C. auris cases in the unit over a 2-year period, despite outbreak response and multimodal mitigation measures. Of the 28 case-patients, 15 (53.6%) were considered colonized and 13 (46.4%) had clinical infections. Phylogenetic analysis of whole-genome sequences revealed 4 distinct clusters of closely related (0-6 SNP differences) genomes containing 3-6 cases. Clusters generally contained temporally related isolates from patients with epidemiologic links; this finding suggests that multiple introductions and within-unit spread over a limited time were responsible for the outbreak, rather than transmission from a long-term source (e.g., persistent environmental contamination or staff carriage). Here, integrated traditional and genomic epidemiology supported C. auris outbreak investigation and response and informed targeted interventions.

Barriers to community engagement during the response to an Ebola virus disease outbreak in Uganda

BackgroundUganda reported an outbreak of Ebola virus disease (EVD) in 2022. As part of the outbreak response, government and partners promoted community engagement, which seeks to involve communities in the...

Integral Scientific Advice for Outbreak Response: Lessons learned from an Avian Influenza Simulation in the Netherlands

Integral Scientific Advice for Outbreak Response: Lessons learned from an Avian Influenza Simulation in the Netherlands

2024 Mpox outbreak response: Drawing a tailored roadmap for improving hospital preparedness and worker awareness in India.

2024 Mpox outbreak response: Drawing a tailored roadmap for improving hospital preparedness and worker awareness in India.

Feasibility of a Mobile Application for Self and Assisted Reporting of Coronavirus Disease 2019 Self-Testing Results in Tanzania: A Pilot Study.

A critical impediment to efficient outbreak response is the availability of timely and complete data on cases and their linkage to care. To inform solutions to this issue, this study investigated the utility of self-testers reporting their coronavirus disease 2019 results using a mobile health platform. Our study has demonstrated that the mobile health platform is feasible; it achieved a 74.5% reporting rate, indicating a strong likelihood of data entry into the unstructured supplementary service data platform. Support from community health workers (CHWs) and healthcare professionals, particularly nurses, contributed to this success, especially among users with limited digital literacy. Specifically, 44.9% of self-test results were submitted by study participants themselves, 24.7% were submitted with the assistance of healthcare professionals, and 30.4% were submitted with the assistance of CHWs. The platform broadens the population base by increasing access and equity, allowing participation even among users without smartphones. Additionally, it integrates rapid antigen diagnostic tests with digital reporting, simplifying data processing and enabling standardized screening, real-time data capture, and effective patient follow-up. This technology also lays a foundation for pandemic preparedness in low- and middle-income countries by demonstrating the feasibility of fully integrating response loops for disease management and interventions. Future response loops could leverage artificial intelligence, machine learning, and integration with existing health surveillance systems, directly benefiting users through enhanced support.

Filovirus outbreak responses and occupational health effects of chlorine spraying in healthcare workers: a systematic review and meta-analysis of alternative disinfectants and application methods.

The authors have withdrawn this manuscript because of data issues that affect the validity of the findings. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Notes from the Field: Genomic and Wastewater Surveillance Data to Guide a Hepatitis A Outbreak Response - Los Angeles County, March 2024-June 2024.

Notes from the Field: Genomic and Wastewater Surveillance Data to Guide a Hepatitis A Outbreak Response - Los Angeles County, March 2024-June 2024.

Resilience of mobility network to dynamic population response across COVID-19 interventions: Evidences from Chile.

The COVID-19 pandemic highlighted the importance of non-traditional data sources, such as mobile phone data, to inform effective public health interventions and monitor adherence to such measures. Previous studies showed how socioeconomic characteristics shaped population response during restrictions and how repeated interventions eroded adherence over time. Less is known about how different population strata changed their response to repeated interventions and how this impacted the resulting mobility network. We study population response during the first and second infection waves of the COVID-19 pandemic in Chile and Spain. Via spatial lag and regression models, we investigate the adherence to mobility interventions at the municipality level in Chile, highlighting the significant role of wealth, labor structure, COVID-19 incidence, and network metrics characterizing business-as-usual municipality connectivity in shaping mobility changes during the two waves. We assess network structural similarities in the two periods by defining mobility hotspots and traveling probabilities in the two countries. As a proof of concept, we simulate and compare outcomes of an epidemic diffusion occurring in the two waves. While differences exist between factors associated with mobility reduction across waves in Chile, underscoring the dynamic nature of population response, our analysis reveals the resilience of the mobility network across the two waves. We test the robustness of our findings recovering similar results for Spain. Finally, epidemic modeling suggests that historical mobility data from past waves can be leveraged to inform future disease spatial invasion models in repeated interventions. This study highlights the value of historical mobile phone data for building pandemic preparedness and lessens the need for real-time data streams for risk assessment and outbreak response. Our work provides valuable insights into the complex interplay of factors driving mobility across repeated interventions, aiding in developing targeted mitigation strategies.

Streamlining whole genome sequencing for clinical diagnostics with ONT technology

Recent advances in whole-genome sequencing (WGS) have increased the accessibility of this tool, offering substantial potential for pathogen surveillance, outbreak response, and diagnostics. However, the routine clinical adoption of WGS is hindered by factors such as high costs, technical complexity, and the requirement for bioinformatics expertise for data analysis. To address these challenges, we propose RapidONT, a workflow designed for cost-effective and accessible WGS-based pathogen analysis. RapidONT employs a mechanical shearing–based DNA extraction protocol, followed by library construction by using a multiplexing Oxford nanopore technologies (ONT) rapid barcoding kit. Flye software is used for de novo assembly without manual intervention, followed by basic assembly polishing using Medaka and Homopolish. The polished assemblies are then analyzed using the user-friendly web-based platform Pathogenwatch, which facilitates species identification, molecular typing, and antimicrobial resistance (AMR) prediction, all while requiring minimal bioinformatics expertise. The efficacy of RapidONT was evaluated using nine clinically relevant pathogens, encompassing a total of 90 gram-positive and gram-negative bacterial strains. The workflow demonstrated high accuracy in critical tasks such as multilocus sequence typing (MLST) and AMR identification, using only ONT R9.4.1 flowcell data. Notably, limitations were observed with Salmonella spp. and Neisseria gonorrhoeae. Furthermore, RapidONT enabled the generation of genomic information for 48 bacterial isolates by using a single flow cell, significantly reducing sequencing costs. This approach eliminates the need for extensive experimentation in obtaining crucial genomic information. This workflow facilitates broader WGS implementation in clinical pathogen analysis and diagnostics.

Dengue Outbreak and Response - Puerto Rico, 2024.

Dengue, a mosquitoborne viral infection, is a public health threat in Puerto Rico, where multiple dengue virus (DENV) serotypes circulate. Dengue causes an acute febrile illness that can progress to severe disease or death. The last outbreak declared by the Puerto Rico Department of Health occurred during 2013. In January 2024, the number of dengue cases in Puerto Rico surpassed the epidemic threshold and remained elevated, prompting the Puerto Rico Department of Health to declare a public health emergency in March 2024. In collaboration with CDC, a dengue outbreak response was initiated to monitor the outbreak and implement vector-control measures alongside public health campaigns to raise awareness about increasing dengue case numbers and strategies to prevent mosquito bites. During 2024, a total of 6,291 confirmed dengue cases were reported; the highest numbers of cases were reported in the municipalities of San Juan (1,200; 17.3%), Carolina (354; 5.1%), and Rincón (252; 3.6%). DENV serotype 3 predominated, accounting for 59.2% of cases with known serotype. Approximately one half of ill patients (52.3%) required hospitalization, with the highest percentages of hospitalizations (33.9%) and severe dengue cases (28.4%) occurring among persons aged 10-19 years. Overall, severe dengue was identified in 4.2% of cases, with 11 reported fatalities (0.2%). Transmission remains elevated in multiple regions, underscoring the need for tailored public health measures, including vaccination among eligible populations, vector management, community outreach, and provider education to facilitate improved outcomes. To reduce the risk for mosquito bites, residents of and visitors to Puerto Rico should consider using repellents, wearing protective clothing, and staying in places with door and window screens.

Ensuring Biosecurity and Research Agility for Outbreak Response: A Researcher’s Perspective on the Federal Nucleic Acid Screening Framework

Ensuring Biosecurity and Research Agility for Outbreak Response: A Researcher’s Perspective on the Federal Nucleic Acid Screening Framework

Leveraging AI for early cholera detection and response: transforming public health surveillance in Nigeria

Cholera continues to pose a significant public health challenge in Nigeria, driven by poor sanitation, inadequate water quality, and climatic factors that create favorable conditions for outbreaks. Since the first epidemic in 1972, Nigeria has experienced recurrent outbreaks, with the most severe in 1991, resulting in over 7,000 deaths. Current surveillance systems and diagnostic methods are limited by infrastructural gaps, insufficient skilled personnel, and inadequate reporting, leading to delays in outbreak detection and response. These limitations exacerbate the public health burden, increasing mortality and the economic impact of cholera epidemics. This paper explores the potential of artificial intelligence (AI) and machine learning (ML) to address these challenges. AI technologies, including predictive modeling and ML algorithms such as random forests and convolutional neural networks (CNNs), can analyze diverse data sources—such as meteorological, environmental, and health records—to detect patterns and predict outbreaks. Case studies from other cholera-endemic regions, where AI achieved high predictive accuracy, demonstrate its transformative potential. By integrating AI into Nigeria’s public health infrastructure, early detection and response can be improved, resource allocation optimized, and disease transmission minimized. However, challenges such as data quality, standardization, and infrastructural deficits must be addressed. Multi-sectoral collaboration involving public health authorities, AI specialists, and policymakers is essential for the successful deployment of these technologies. This article concludes that AI-powered cholera surveillance systems have the potential to revolutionize public health outcomes, reducing cholera-related morbidity and mortality in resource-limited settings like Nigeria.

‘Involve those who are managing these outbreaks’: stakeholders’ perspectives on the barriers and facilitators to the implementation of clinical management guidelines for high-consequence infectious diseases in Uganda—a thematic network analysis

IntroductionPrior research highlighting the complexity of clinical management guidelines’ (CMGs) implementation during high consequence infectious disease (HCID) outbreaks has suggested that limited access to treatments and equipment and substantial issues...

A Call for Action: Lessons Learned From a Pilot to Share a Complex, Linked COVID-19 Cohort Dataset for Open Science.

The COVID-19 pandemic proved how sharing of genomic sequences in a timely manner, as well as early detection and surveillance of variants and characterization of their clinical impacts, helped to inform public health responses. However, the area of (re)emerging infectious diseases and our global connectivity require interdisciplinary collaborations to happen at local, national and international levels and connecting data to understand the linkages between all factors involved. Here, we describe experiences and lessons learned from a COVID-19 pilot study aimed at developing a model for storage and sharing linked laboratory data and clinical-epidemiological data using European open science infrastructure. We provide insights into the barriers and complexities of internationally sharing linked, complex cohort datasets from opportunistic studies for connected data analyses. An analytical timeline of events, describing key actions and delays in the execution of the pilot, and a critical path, defining steps in the process of internationally sharing a linked cohort dataset are included. The pilot showed how building on existing infrastructure that had previously been developed within the European Nucleotide Archive at the European Molecular Biology Laboratory-European Bioinformatics Institute for pathogen genomics data sharing, allowed the rapid development of connected "data hubs." These data hubs were required to link human clinical-epidemiological data under controlled access with open high dimensional laboratory data, under FAIR (Findable, Accessible, Interoperable, Reusable) principles. Based on our own experiences, we call for action and make recommendations to support and to improve data sharing for outbreak preparedness and response.

U.S. NAMRU SOUTH's Insights and Contributions to Diagnostics in the Context of Malaria Elimination.

Timely and accurate diagnosis is a critical aspect of malaria surveillance, treatment, and intervention campaigns. Currently, field malaria diagnostics rely almost primarily on light microscopy and rapid diagnostic tests. However, both methods miss a significant proportion of asymptomatic patients and perform poorly in low transmission settings. In this review, we present tools that have been used by U.S. Naval Medical Research Unit (NAMRU) SOUTH and its collaborators during the last 40 years for various aspects of malaria research, including clinical trials, outbreak response, and epidemiologic surveillance in South and Central America. Overall, the current and future toolbox for malaria diagnostics needs to be carefully evaluated and tailored to the malaria transmission dynamics in each focus to maximize its effectiveness and achieve the goal of malaria elimination.

Elucidating Infectious Causes of Fever of Unknown Origin: A Laboratory-Based Observational Study of Patients with Suspected Ebola Virus Disease, Guinea, 2014.

The etiology of fever of unknown origin (FUO) in sub-Saharan Africa often remains unexplained. We performed a retrospective laboratory-based observational study of 550 Guinean patients with FUO testing negative for Ebola virus from March to December 2014. Blood-borne pathogens were diagnosed by polymerase chain reaction (PCR) or reverse transcription-PCR (RT-PCR), serologic tests, and targeted and unbiased high-throughput sequencing (HTS). In 275 of 550 individuals, we found evidence of ≥1 pathogen by molecular methods. We identified Plasmodium in 35.6% of patients via PCR, with P falciparum constituting 96.4% of these cases. Pathogenic bacteria, including Salmonella and Klebsiella, were detected in 18.4% of patients through PCR and HTS. Resistance determinants against first-line antibiotics were found in 26.9% of pooled sera by HTS. Yellow fever, Lassa, and Ebola viruses were detected in 5.8% of patients by RT-PCR; HTS-guided RT-PCR confirmed Orungo virus infection in 1 patient. Phylogenetic analyses revealed that the viral genomes matched the available genomic data in terms of location and time. Indirect immunofluorescence assays revealed immunoglobulin M antibodies against yellow fever, Ebola, dengue, West Nile, and Crimean Congo hemorrhagic fever viruses in 11 of 100 patients who were PCR or RT-PCR negative. One in 5 patients who were infected presented coinfections, predominantly malaria associated with sepsis-causing bacteria, in adults (12.1%) and children (12.5%), whereas viral coinfections were rare. Patients presented fever (74.7%), asthenia (67.7%), emesis (38.2%), diarrhea (28.3%), and hemorrhage (11.8%), without clear etiology associations. An exhaustive laboratory investigation elucidated infectious causes of FUO in 52.3% of patients. Quality control and strengthening laboratory capacities in sub-Saharan Africa are essential for patient care, outbreak response, and regionally appropriate diagnostics.