Climate change and inequality.

This review explores how climate change is manifesting along existing lines of inequality and thus further exacerbating current health disparities with a particular focus on children and future generations. Climate change risk and vulnerability are not equally distributed, nor is the adaptive capacity to respond to its adverse effects, which include health consequences, economic impacts, and displacement. Existing lines of inequality are already magnifying the adverse effects of climate change. Today's children and future generations will experience a disproportionate number of adverse climate events than prior generations, especially children in lower-income populations, communities of color, and Indigenous communities. In order to mitigate the crisis of inequity accompanying the climate crisis, systemic action must be taken on a global scale - with a focus on protecting children and future generations, and in empowering youth-led environmental activism and engagement in climate policy. IMPACT STATEMENT: Our review offers a current summary of the ways in which inequality is manifesting with respect to climate change in children and future generations. Rather than use a systematic review, we opted to use a theoretical framework to guide our review. We divided the effects of climate change into three effect pathways: via disruptions in (i) climate and weather, (ii) ecosystems, and (iii) society. By dividing our review in this theoretical framework, we can better suggest targeted public health interventions at each effect level. Furthermore, we are able to successfully identify literature gaps and areas of future research.

Improving rural health care reduces illegal logging and conserves carbon in a tropical forest.

Tropical forest loss currently exceeds forest gain, leading to a net greenhouse gas emission that exacerbates global climate change. This has sparked scientific debate on how to achieve natural climate solutions. Central to this debate is whether sustainably managing forests and protected areas will deliver global climate mitigation benefits, while ensuring local peoples' health and well-being. Here, we evaluate the 10-y impact of a human-centered solution to achieve natural climate mitigation through reductions in illegal logging in rural Borneo: an intervention aimed at expanding health care access and use for communities living near a national park, with clinic discounts offsetting costs historically met through illegal logging. Conservation, education, and alternative livelihood programs were also offered. We hypothesized that this would lead to improved health and well-being, while also alleviating illegal logging activity within the protected forest. We estimated that 27.4 km2 of deforestation was averted in the national park over a decade (∼70% reduction in deforestation compared to a synthetic control, permuted P = 0.038). Concurrently, the intervention provided health care access to more than 28,400 unique patients, with clinic usage and patient visitation frequency highest in communities participating in the intervention. Finally, we observed a dose-response in forest change rate to intervention engagement (person-contacts with intervention activities) across communities bordering the park: The greatest logging reductions were adjacent to the most highly engaged villages. Results suggest that this community-derived solution simultaneously improved health care access for local and indigenous communities and sustainably conserved carbon stocks in a protected tropical forest.

Clinical Outcomes, Echocardiographic Findings, and Care Quality Metrics for People Living With Human Immunodeficiency Virus (HIV) and Rheumatic Heart Disease in Uganda.

BACKGROUND: Rheumatic heart disease (RHD) affects 41 million people worldwide, mostly in low- and middle-income countries, where it is co-endemic with human immunodeficiency virus (HIV). HIV is also a chronic inflammatory disorder associated with cardiovascular complications, yet the epidemiology of patients affected by both diseases is poorly understood. METHODS: Utilizing the Uganda National RHD Registry, we described the echocardiographic findings, clinical characteristics, medication prescription rates, and outcomes of all 73 people carrying concurrent diagnoses of HIV and RHD between 2009 and 2018. These individuals were compared to an age- and sex-matched cohort of 365 subjects with RHD only. RESULTS: The median age of the HIV-RHD group was 36 years (interquartile range [IQR] 15), and 86% were women. The HIV-RHD cohort had higher rates of prior stroke/transient ischemic attack (12% vs 5%, P = .02) than the RHD-only group, with this association persisting following multivariable adjustment (odds ratio [OR] 3.08, P = .03). Prevalence of other comorbidities, echocardiographic findings, prophylactic penicillin prescription rates, retention in clinical care, and mortality were similar between the 2 groups. CONCLUSIONS: Patients living with RHD and HIV in Uganda are a relatively young, predominantly female group. Although RHD-HIV comorbid individuals have higher rates of stroke, their similar all-cause mortality and RHD care quality metrics (such as retention in care) compared to those with RHD alone suggest rheumatic heart disease defines their clinical outcome more than HIV does. We believe this study to be one of the first reports of the epidemiologic profile and longitudinal outcomes of patients who carry diagnoses of both conditions.

The political and security dimensions of the humanitarian health response to violent conflict.

The nature of armed conflict throughout the world is intensely dynamic. Consequently, the protection of non-combatants and the provision of humanitarian services must continually adapt to this changing conflict environment. Complex political affiliations, the systematic use of explosive weapons and sexual violence, and the use of new communication technology, including social media, have created new challenges for humanitarian actors in negotiating access to affected populations and security for their own personnel. The nature of combatants has also evolved as armed, non-state actors might have varying motivations, use different forms of violence, and engage in a variety of criminal activities to generate requisite funds. New health threats, such as the COVID-19 pandemic, and new capabilities, such as modern trauma care, have also created new challenges and opportunities for humanitarian health provision. In response, humanitarian policies and practices must develop negotiation and safety capabilities, informed by political and security realities on the ground, and guidance from affected communities. More fundamentally, humanitarian policies will need to confront a changing geopolitical environment, in which traditional humanitarian norms and protections might encounter wavering support in the years to come.

Climate change and global health: A call to more research and more action.

There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political, and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.

The impact of novel coronavirus COVID-19 on noncommunicable disease patients and health systems: a review.

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic affecting all levels of health systems. This includes the care of patients with noncommunicable diseases (NCDs) who bear a disproportionate burden of both COVID-19 itself and the public health measures enacted to combat it. In this review, we summarize major COVID-19-related considerations for NCD patients and their care providers, focusing on cardiovascular, pulmonary, renal, haematologic, oncologic, traumatic, obstetric/gynaecologic, operative, psychiatric, rheumatologic/immunologic, neurologic, gastrointestinal, ophthalmologic and endocrine disorders. Additionally, we offer a general framework for categorizing the pandemic's disruptions by disease-specific factors, direct health system factors and indirect health system factors. We also provide references to major NCD medical specialty professional society statements and guidelines on COVID-19. COVID-19 and its control policies have already resulted in major disruptions to the screening, treatment and surveillance of NCD patients. In addition, it differentially impacts those with pre-existing NCDs and may lead to de novo NCD sequelae. Likely, there will be long-term effects from this pandemic that will continue to affect practitioners and patients in this field for years to come.

Global health security as it pertains to Zika, Ebola, and COVID-19.

PURPOSE OF REVIEW: Due to the impact of the COVID-19 pandemic this past year, we have witnessed a significant acceleration in the science, technology, and policy of global health security. This review highlights important progress made toward the mitigation of Zika, Ebola, and COVID-19 outbreaks. These epidemics and their shared features suggest a unified policy and technology agenda that could broadly improve global health security. RECENT FINDINGS: Molecular epidemiology is not yet in widespread use, but shows promise toward informing on-the-ground decision-making during outbreaks. Point-of-care (POC) diagnostics have been achieved for each of these threats; however, deployment of Zika and Ebola diagnostics lags behind those for COVID-19. POC metagenomics offers the possibility of identifying novel viruses. Vaccines have been successfully approved for Ebola and COVID-19, due in large part to public-private partnerships and advance purchase commitments. Therapeutics trials conducted during ongoing epidemics have identified effective antibody therapeutics for Ebola, as well as steroids (both inhaled and oral) and a broad-spectrum antiviral for COVID-19. SUMMARY: Achieving global health security remains a challenge, though headway has been made over the past years. Promising policy and technology strategies that would increase resilience across emerging viral pathogens should be pursued.

Estimating the local spatio-temporal distribution of malaria from routine health information systems in areas of low health care access and reporting.

BACKGROUND: Reliable surveillance systems are essential for identifying disease outbreaks and allocating resources to ensure universal access to diagnostics and treatment for endemic diseases. Yet, most countries with high disease burdens rely entirely on facility-based passive surveillance systems, which miss the vast majority of cases in rural settings with low access to health care. This is especially true for malaria, for which the World Health Organization estimates that routine surveillance detects only 14% of global cases. The goal of this study was to develop a novel method to obtain accurate estimates of disease spatio-temporal incidence at very local scales from routine passive surveillance, less biased by populations' financial and geographic access to care. METHODS: We use a geographically explicit dataset with residences of the 73,022 malaria cases confirmed at health centers in the Ifanadiana District in Madagascar from 2014 to 2017. Malaria incidence was adjusted to account for underreporting due to stock-outs of rapid diagnostic tests and variable access to healthcare. A benchmark multiplier was combined with a health care utilization index obtained from statistical models of non-malaria patients. Variations to the multiplier and several strategies for pooling neighboring communities together were explored to allow for fine-tuning of the final estimates. Separate analyses were carried out for individuals of all ages and for children under five. Cross-validation criteria were developed based on overall incidence, trends in financial and geographical access to health care, and consistency with geographic distribution in a district-representative cohort. The most plausible sets of estimates were then identified based on these criteria. RESULTS: Passive surveillance was estimated to have missed about 4 in every 5 malaria cases among all individuals and 2 out of every 3 cases among children under five. Adjusted malaria estimates were less biased by differences in populations' financial and geographic access to care. Average adjusted monthly malaria incidence was nearly four times higher during the high transmission season than during the low transmission season. By gathering patient-level data and removing systematic biases in the dataset, the spatial resolution of passive malaria surveillance was improved over ten-fold. Geographic distribution in the adjusted dataset revealed high transmission clusters in low elevation areas in the northeast and southeast of the district that were stable across seasons and transmission years. CONCLUSIONS: Understanding local disease dynamics from routine passive surveillance data can be a key step towards achieving universal access to diagnostics and treatment. Methods presented here could be scaled-up thanks to the increasing availability of e-health disease surveillance platforms for malaria and other diseases across the developing world.

Health interventions among mobile pastoralists: a systematic review to guide health service design.

OBJECTIVE: Mobile pastoralists are one of the last populations to be reached by health services and are frequently missed by health campaigns. Since health interventions among pastoralists have been staged across a range of disciplines but have not yet been systematically characterised, we set out to fill this gap. METHODS: We conducted a systematic search in PubMed/MEDLINE, Scopus, Embase, CINAL, Web of Science, WHO Catalog, AGRICOLA, CABI, ScIELO, Google Scholar and grey literature repositories to identify records that described health interventions, facilitators and barriers to intervention success, and factors influencing healthcare utilisation among mobile pastoralists. No date restrictions were applied. Due to the heterogeneity of reports captured in this review, data were primarily synthesised through narrative analysis. Descriptive statistical analysis was performed for data elements presented by a majority of records. RESULTS: Our search yielded 4884 non-duplicate records, of which 140 eligible reports were included in analysis. 89.3% of reports presented data from sub-Saharan Africa, predominantly in East Africa (e.g. Ethiopia, 30.0%; Kenya, 17.1%). Only 24.3% of reports described an interventional study, while the remaining 75.7% described secondary data of interest on healthcare utilisation. Only two randomised controlled trials were present in our analysis, and only five reports presented data on cost. The most common facilitators of intervention success were cultural sensitivity (n = 16), community engagement (n = 12) and service mobility (n = 11). CONCLUSION: Without adaptations to account for mobile pastoralists' unique subsistence patterns and cultural context, formal health services leave pastoralists behind. Research gaps, including neglect of certain geographic regions, lack of both interventional studies and diversity of study design, and limited data on economic feasibility of interventions must be addressed to inform the design of health services capable of reaching mobile pastoralists. Pastoralist-specific delivery strategies, such as combinations of mobile and 'temporary fixed' services informed by transhumance patterns, culturally acceptable waiting homes, community-directed interventions and combined joint human-animal One Health design as well as the bundling of other health services, have shown initial promise upon which future work should build.

OBJECTIF: Les éleveurs nomades sont l'une des dernières populations à être touchées par les services de santé et sont souvent ratés par les campagnes de santé. Etant donné que les interventions de santé parmi ces éleveurs ont été programmées dans une gamme de disciplines mais n'ont pas encore été systématiquement caractérisées, nous avons entrepris de combler cette lacune. MÉTHODES: Nous avons effectué une recherche systématique dans les répertoires PubMed/MEDLINE, Scopus, EMBASE, CINAL, Web of Science, WHO Catalog, AGRICOLA, CABI, ScIELO, Google Scholar et de la littérature grise pour identifier les reports décrivant les interventions de santé, les facilitateurs et les obstacles au succès de l'intervention ainsi que les facteurs influençant l'utilisation des soins de santé chez les éleveurs nomades. Aucune restriction de date n'a été appliquée. En raison de l'hétérogénéité des rapports capturés dans cette revue, les données ont été principalement synthétisées au moyen d'une analyse narrative. Une analyse statistique descriptive a été effectuée pour les éléments de données présentés par une majorité des reports. RÉSULTATS: Notre recherche a révélé 4.884 rapports non dupliqués, dont 140 éligibles ont été inclus dans l'analyse. 89,3% des rapports présentaient des données d'Afrique subsaharienne, principalement en Afrique de l'Est (ex: Ethiopie, 30,0%; Kenya, 17,1%). Seuls 24,3% des rapports décrivaient une étude interventionnelle, tandis que les 75,7% restants décrivaient des données d'intérêt secondaires sur l'utilisation des soins de santé. Seuls deux essais contrôlés randomisés étaient présents dans notre analyse, et seuls cinq rapports présentaient des données sur le coût. Les facilitateurs les plus courants du succès des interventions étaient la sensibilité culturelle (n=16), l'engagement communautaire (n=12) et la mobilité des services (n=11). CONCLUSION: Sans adaptations pour tenir compte des modèles de subsistance et du contexte culturel uniques des éleveurs nomades, les services de santé formels les laissent de côté. Les lacunes de la recherche, y compris la négligence de certaines régions géographiques, le manque d'études interventionnelles et la diversité de la conception des études, et les données limitées sur la faisabilité économique des interventions doivent être comblées pour éclairer la conception de services de santé capables d'atteindre les éleveurs nomades. Des stratégies de prestation spécifiques aux éleveurs nomades, telles que des combinaisons de services mobiles et «fixes temporaires¼ éclairés par des schémas de transhumance, des maisons d'attente culturellement acceptables, des interventions dirigées par la communauté et une conception conjointe d'une seule santé homme-animal ainsi que le regroupement d'autres services de santé, ont montré une promesse initiale sur laquelle les travaux futurs devraient s'appuyer.

Expression of the Vaccinia Virus Antiapoptotic F1 Protein Is Blocked by Protein Kinase R in the Absence of the Viral E3 Protein.

Poxviruses encode many proteins with the ability to regulate cellular signaling pathways. One such protein is the vaccinia virus innate immunity modulator E3. Multiple functions have been ascribed to E3, including modulating the cellular response to double-stranded RNA, inhibiting the NF-κB and IRF3 pathways, and dampening apoptosis. Apoptosis serves as a powerful defense against damaged and unwanted cells and is an effective defense against viral infection; many viruses therefore encode proteins that prevent or delay apoptosis. Here, we present data indicating that E3 does not directly inhibit the intrinsic apoptotic pathway; instead, it suppresses apoptosis indirectly by stimulating expression of the viral F1 apoptotic inhibitor. Our data demonstrate that E3 promotes F1 expression by blocking activation of the double-stranded RNA-activated protein kinase R (PKR). F1 mRNA is present in cells infected with E3-null virus, but the protein product does not detectably accumulate, suggesting a block at the translational level. We also show that two 3' coterminal transcripts span the F1 open reading frame (ORF), a situation previously described for the vaccinia virus mRNAs encoding the J3 and J4 proteins. One of these is a conventional monocistronic transcript of the F1L gene, while the other arises by read-through transcription from the upstream F2L gene and does not give rise to appreciable levels of F1 protein.IMPORTANCE Previous studies have shown that E3-deficient vaccinia virus triggers apoptosis of infected cells. Our study demonstrates that this proapoptotic phenotype stems, at least in part, from the failure of the mutant virus to produce adequate quantities of the viral F1 protein, which acts at the mitochondria to directly block apoptosis. Our data establish a regulatory link between the vaccinia virus proteins that suppress the innate response to double-stranded RNA and those that block the intrinsic apoptotic pathway.

Timely access to care for patients with critical burns in India: a prehospital prospective observational study.

BACKGROUND: Low/middle-income countries carry a disproportionate burden of the morbidity and mortality from thermal burns. Nearly 70% of burn deaths worldwide are from thermal burns in India. Delays to medical care are commonplace and an important predictor of outcomes. We sought to understand the role of emergency medical services (EMS) as part of the healthcare infrastructure for thermal burns in India. METHODS: We conducted a prospective observational study of patients using EMS for thermal burns across five Indian states from May to August 2015. Our primary outcome was mortality at 2, 7 and 30 days. We compared observed mortality with expected mortality using the revised Baux score. We used Χ2 analysis for categorical variables and Wilcoxon two-sample test for continuous variables. ORs and 95% CIs are reported for all modelled predictor variables. RESULTS: We enrolled 439 patients. The 30-day follow-up rate was 85.9% (n=377). The median age was 30 years; 56.7% (n=249) lived in poverty; and 65.6% (n=288) were women. EMS transported 94.3% of patients (n=399) to the hospital within 2 hours of their call. Median total body surface area (TBSA) burned was 60% overall, and 80% in non-accidental burns. Sixty-eight per cent of patients had revised Baux scores greater than 80. Overall 30-day mortality was 64.5%, and highest (90.2%) in women with non-accidental burns. Predictors of mortality by multivariate regression were TBSA (OR 7.9), inhalation injury (OR 5.5), intentionality (OR 4.7) and gender (OR 2.2). DISCUSSION: Although EMS rapidly connects critically burned patients to care in India, mortality remains high, with women disproportionally suffering self-inflicted burns. To combat the burn epidemic in India, efforts must focus on rapid medical care and critical care services, and on a burn prevention strategy that includes mental health and gender-based violence support services.

Community outreach programs and major adherence lapses with antiretroviral therapy in rural Kakamega, Kenya.

We investigated features of major adherence lapses in antiretroviral therapy (ART) at public Emusanda Health Centre in rural Kakamega County, Kenya using medical records from 2008 to 2015 for all 306 eligible patients receiving ART. Data were modelled using survival analysis. Patients were more likely to lapse if they received stavudine (hazard ratio (HR) 2.54, 95% confidence interval (95%CI):1.44-4.47) or zidovudine (HR 1.64, 95%CI:1.02-2.63) relative to tenofovir. Each day a patient slept hungry per month increased risk of major adherence lapse by 3% (95%CI:0-7%). Isolated home visits by community health workers (CHWs) were more effective to assist patients to return to the health centre than isolated phone calls (HR 2.52, 95%CI:1.02-6.20).

Institutionalizing healthcare hackathons to promote diversity in collaboration in medicine.

BACKGROUND: Medical students and healthcare professionals can benefit from exposure to cross-disciplinary teamwork and core concepts of medical innovation. Indeed, to address complex challenges in patient care, diversity in collaboration across medicine, engineering, business, and design is critical. However, a limited number of academic institutions have established cross-disciplinary opportunities for students and young professionals within these domains to work collaboratively towards diverse healthcare needs. METHODS: Drawing upon best practices from computer science and engineering, healthcare hackathons bring together interdisciplinary teams of students and professionals to collaborate, brainstorm, and build solutions to unmet clinical needs. Over the course of six months, a committee of 20 undergraduates, medical students, and physician advisors organized Stanford University's first healthcare hackathon (November 2016). Demographic data from initial applications were supplemented with responses from a post-hackathon survey gauging themes of diversity in collaboration, professional development, interest in medical innovation, and educational value. In designing and evaluating the event, the committee focused on measurable outcomes of diversity across participants (skillset, age, gender, academic degree), ideas (clinical needs), and innovations (projects). RESULTS: Demographic data (n = 587 applicants, n = 257 participants) reveal participants across diverse academic backgrounds, age groups, and domains of expertise were in attendance. From 50 clinical needs presented representing 19 academic fields, 40 teams ultimately formed and submitted projects spanning web (n = 13) and mobile applications (n = 13), artificial intelligence-based tools (n = 6), and medical devices (n = 3), among others. In post-hackathon survey responses (n = 111), medical students and healthcare professionals alike noted a positive impact on their ability to work in multidisciplinary teams, learn from individuals of different backgrounds, and address complex healthcare challenges. CONCLUSIONS: Healthcare hackathons can encourage diversity across individuals, ideas, and projects to address clinical challenges. By providing an outline of Stanford's inaugural event, we hope more universities can adopt the healthcare hackathon model to promote diversity in collaboration in medicine.

The N Terminus of the Vaccinia Virus Protein F1L Is an Intrinsically Unstructured Region That Is Not Involved in Apoptosis Regulation.

Subversion of host cell apoptotic responses is a prominent feature of viral immune evasion strategies to prevent premature clearance of infected cells. Numerous poxviruses encode structural and functional homologs of the Bcl-2 family of proteins, and vaccinia virus harbors antiapoptotic F1L that potently inhibits the mitochondrial apoptotic checkpoint. Recently F1L has been assigned a caspase-9 inhibitory function attributed to an N-terminal α helical region of F1L spanning residues 1-15 (1) preceding the domain-swapped Bcl-2-like domains. Using a reconstituted caspase inhibition assay in yeast we found that unlike AcP35, a well characterized caspase-9 inhibitor from the insect virus Autographa californica multiple nucleopolyhedrovirus, F1L does not prevent caspase-9-mediated yeast cell death. Furthermore, we found that deletion of the F1L N-terminal region does not impede F1L antiapoptotic activity in the context of a viral infection. Solution analysis of the F1L N-terminal regions using small angle x-ray scattering indicates that the region of F1L spanning residues 1-50 located N-terminally from the Bcl-2 fold is an intrinsically unstructured region. We conclude that the N terminus of F1L is not involved in apoptosis inhibition and may act as a regulatory element in other signaling pathways in a manner reminiscent of other unstructured regulatory elements commonly found in mammalian prosurvival Bcl-2 members including Bcl-xL and Mcl-1.

Which perseverative behaviors are symptoms of spatial neglect?

Spatial neglect is a characterized by a failure to attend or make movements towards left-sided stimuli. Common paper-and-pencil tasks to diagnose spatial neglect are sensitive to perseverative errors, including additional marks over already cancelled targets and "scribbling" out a target. Here, we examine whether functionally distinct perseverative behaviors are related to spatial neglect. Line cancellation tasks of 45 healthy controls and 220 right-hemisphere stroke survivors were examined for recurrent marks (RM) and continuous marks (CM) perseverations. We found that RM perseveration correlated with neglect severity, while CM perseveration did not. Examination of lesion profiles for the two groups indicated distinct anatomical correlates, with RM lesions overlapping regions implicated in spatial neglect including the rolandic operculum, superior temporal gyrus, and inferior parietal lobule.

EVM005: an ectromelia-encoded protein with dual roles in NF-κB inhibition and virulence.

Poxviruses contain large dsDNA genomes encoding numerous open reading frames that manipulate cellular signalling pathways and interfere with the host immune response. The NF-κB signalling cascade is an important mediator of innate immunity and inflammation, and is tightly regulated by ubiquitination at several key points. A critical step in NF-κB activation is the ubiquitination and degradation of the inhibitor of kappaB (IκBα), by the cellular SCFß-TRCP ubiquitin ligase complex. We show here that upon stimulation with TNFα or IL-1ß, Orthopoxvirus-infected cells displayed an accumulation of phosphorylated IκBα, indicating that NF-κB activation was inhibited during poxvirus infection. Ectromelia virus is the causative agent of lethal mousepox, a natural disease that is fatal in mice. Previously, we identified a family of four ectromelia virus genes (EVM002, EVM005, EVM154 and EVM165) that contain N-terminal ankyrin repeats and C-terminal F-box domains that interact with the cellular SCF ubiquitin ligase complex. Since degradation of IκBα is catalyzed by the SCFß-TRCP ubiquitin ligase, we investigated the role of the ectromelia virus ankyrin/F-box protein, EVM005, in the regulation of NF-κB. Expression of Flag-EVM005 inhibited both TNFα- and IL-1ß-stimulated IκBα degradation and p65 nuclear translocation. Inhibition of the NF-κB pathway by EVM005 was dependent on the F-box domain, and interaction with the SCF complex. Additionally, ectromelia virus devoid of EVM005 was shown to inhibit NF-κB activation, despite lacking the EVM005 open reading frame. Finally, ectromelia virus devoid of EVM005 was attenuated in both A/NCR and C57BL/6 mouse models, indicating that EVM005 is required for virulence and immune regulation in vivo.