Designing a smallpox B-cell and T-cell multi-epitope subunit vaccine using a comprehensive immunoinformatics approach.

Smallpox is a highly contagious human disease caused by the variola virus. Although the disease was eliminated in 1979 due to its highly contagious nature and historical pathogenicity, with a mortality rate of up to 30%, this virus is an important candidate for biological weapons. Currently, vaccines are the critical measures to prevent this virus infection and spread. In this study, we designed a peptide vaccine using immunoinformatics tools, which have the potential to activate human immunity against variola virus infection efficiently. The design of peptides derives from vaccine-candidate proteins showing protective potential in vaccinia WR strains. Potential non-toxic and nonallergenic T-cell and B-cell binding and cytokine-inducing epitopes were then screened through a priority prediction using special linkers to connect B-cell epitopes and T-cell epitopes, and an appropriate adjuvant was added to the vaccine construction to enhance the immunogenicity of the peptide vaccine. The 3D structure display, docking, and free energy calculation analysis indicate that the binding affinity between the vaccine peptide and Toll-like receptor 3 is high, and the vaccine receptor complex is highly stable. Notably, the vaccine we designed is obtained from the protective protein of the vaccinia and combined with preventive measures to avoid side effects. This vaccine is highly likely to produce an effective and safe immune response against the variola virus infection in the body. IMPORTANCE: In this work, we designed a vaccine with a cluster of multiple T-cell/B-cell epitopes, which should be effective in inducing systematic immune responses against variola virus infection. Besides, this work also provides a reference in vaccine design for preventing monkeypox virus infection, which is currently prevalent.

Biology of Variola Virus.

Variola virus is an anthroponotic agent that belongs to the orthopoxvirus family. It is an etiological agent of smallpox, an ancient disease that caused massive mortality of human populations. Twentieth century has witnessed the death of about 300 million people due to the unavailability of an effective vaccine. Early detection is the primary strategy to prevent an outbreak of smallpox. Variola virus forms the characteristic pus-filled pustules and centrifugal rash distribution in the infected patients while transmission occurs mainly through respiratory droplets during the early stage of infection. No antiviral drugs are approved for variola virus till date. Generation of first-generation vaccines helped in the eradication of smallpox which was declared by the World Health Organization.

Poxviridae Pneumonia.

Poxviridae family includes several viruses that infecting humans usually causes skin lesions only, but in some cases their clinical course is complicated by viral pneumonia (with or without bacterial superinfections). Historically variola virus has been the poxviridae most frequently associated with the development of pneumonia with many large outbreaks worldwide before its eradication in 1980. It is still considered a biological threat for its potential in biological warfare and bioterrorism. Smallpox pneumonia can be severe with the onset of acute respiratory distress syndrome (ARDS) and death. Vaccinia virus, used for vaccination against smallpox exceptionally, in immunocompromised patients, can induce generalized (with also lung involvement) severe disease after vaccination. MPXV virus occasionally can cause pneumonia particularly in immunocompromised patients. The pathophysiology of poxviridae pneumonia is still an area of active research; however, in animal models these viruses can cause both direct damage to the lower airways epithelium and a hyperinflammatory syndrome, like a cytokine storm. Multiple mechanisms of immune evasion have also been described. The treatment of poxviridae pneumonia is mainly based on careful supportive care. Despite the absence of randomized clinical trials in patients with poxviridae pneumonia there are antiviral drugs, such as tecovirimat, cidofovir and brincidofovir, FDA-approved for use in smallpox and also available under an expanded access protocol for treatment of MPXV. There are 2 (replication-deficient modified vaccinia Ankara and replication-competent vaccinia virus) smallpox vaccines FDA-approved with the first one also approved for prevention of MPXV in adults that are at high risk of infection.

Treatment and Vaccination for Smallpox and Monkeypox.

The smallpox infection with the variola virus was one of the most fatal disorders until a global eradication was initiated in the twentieth century. The last cases were reported in Somalia 1977 and as a laboratory infection in the UK 1978; in 1980, the World Health Organization (WHO) declared smallpox for extinct. The smallpox virus with its very high transmissibility and mortality is still a major biothreat, because the vaccination against smallpox was stopped globally in the 1980s. For this reason, new antivirals (cidofovir, brincidofovir, and tecovirimat) and new vaccines (ACAM2000, LC16m8 and Modified Vaccine Ankara MVA) were developed. For passive immunization, vaccinia immune globulin intravenous (VIGIV) is available. Due to the relationships between orthopox viruses such as vaccinia, variola, mpox (monkeypox), cowpox, and horsepox, the vaccines (LC16m8 and MVA) and antivirals (brincidofovir and tecovirimat) could also be used in the mpox outbreak with positive preliminary data. As mutations can result in drug resistance against cidofovir or tecovirimat, there is need for further research. Further antivirals (NIOCH-14 and ST-357) and vaccines (VACΔ6 and TNX-801) are being developed in Russia and the USA. In conclusion, further research for treatment and prevention of orthopox infections is needed and is already in progress. After a brief introduction, this chapter presents the smallpox and mpox disease and thereafter full overviews on antiviral treatment and vaccination including the passive immunization with vaccinia immunoglobulins.

Two cases of smallpox from 1540 CE circum-contact (early colonial) Northern Coastal Peru.

OBJECTIVE: This project seeks to create a differential diagnosis for lesions found on the skeletal remains of two children as a means to explore the presence of viral disease in 16th- century Peru. MATERIALS: Extremely well-preserved human remains of two children who died between the ages of 1-2 years old, recovered from the circum-contact (∼1540 CE) cemetery in Huanchaco, Peru. METHODS: Macroscopic and radiographic analysis. RESULTS: Both individuals present with cortical thickening, symmetrical destructive lesions, metaphyseal expansion, perforations, exposure of the medullary cavity, resorption of metaphyseal ends and necrosis of the long bones, and deposited reactive new bone. These features are consistent with osteomyelitis variolosa and bacterial osteomyelitis. CONCLUSIONS: Three features of Individuals IG-124 and IG-493 suggest a highly consistent diagnosis of osteomyelitis variolosa: multiple skeletal lesions, the historical context of the area, and the high mortality rate of non-adults in the circum-contact cemetery. SIGNIFICANCE: Although viral infections are ubiquitous and well documented historically, their etiologies are often difficult to determine in archaeological populations. Orthopoxvirus variola (smallpox) is one of the many viruses whose archaeological impact is still under explored in skeletal remains. LIMITATIONS: The absence of smallpox in other children from the Huanchaco cemetery creates difficulty in ascertaining true prevalence rates or information on potential outbreaks. SUGGESTIONS FOR FURTHER RESEARCH: Further research analyzing aDNA from calculus and/or residues using a DIP-GC-MS method might create a better understanding of how smallpox spread through the region.

Ações contra monkeypox em unidade de urgência e emergência: relato de experiência / Actions against monkeypox in a urgency and emergency unit: experience report / Acciones contra la viruela del mono en una unidad de urgencias y emergencias: reporte de experiencia

A monkeypox, ou mpox, consiste em uma nova problemática em saúde pública, que exige ações imediatas para seu controle. Diante disso, este relato de experiência visou relatar as fragilidades nas ações de controle da monkeypox em unidades de urgência e emergência em Fortaleza, Brasil, de 10 de agosto a 20 de novembro de 2022. Utilizou-se a análise temática para organização das categorias nos resultados e o referencial teórico da racionalidade limitada de Herbert Simon para discussão. Duas categorias surgiram: capacitação para identificação e manejo de monkeypox pelos profissionais de saúde; e desafios nas ações contra monkeypox em unidades de pronto atendimento. Apesar de ações iniciais significativas para contenção da doença, ainda há fragilidades na capacitação de recursos humanos, na vigilância em saúde e na qualidade da detecção de casos, que podem impactar o controle da doença e aumentar sua infectividade, morbidade e mortalidade futura.

Monkeypox or mpox configures a new public health problem that requires immediate action to control it. Thus, this experience report aimed to describe weaknesses in control actions against monkeypox in urgency and emergency units in Fortaleza, Brazil, from August 10 to November 20, 2022. Thematic analysis was used to organize the categories in results and in the theoretical framework of Herbert Simon's Limited Rationality for discussion. Overall, two categories emerged: Training so healthcare providers can identify and manage monkeypox and Challenges in actions against the disease in emergency care units. Despite significant initial actions to contain the disease, weaknesses remain in the training of human resources, health surveillance, and the quality of case detection, which can impact disease control and increase its future infectivity, morbidity, and mortality.

La viruela del mono es un nuevo problema de salud pública que requiere acciones inmediatas para controlarla. Ante esto, este reporte de experiencia tuvo como objetivo reportar debilidades en las acciones de control contra la viruela del mono en las unidades de urgencias y emergencias en Fortaleza, Brasil, en el período del 10 de agosto al 20 de noviembre de 2022. Se utilizaron el análisis temático para organizar las categorías en los resultados y el marco teórico de la racionalidad limitada de Herbert Simon para la discusión. Surgieron dos categorías: Capacitación para la identificación y manejo de la viruela del mono por parte de profesionales de la salud; y desafíos en las acciones contra la enfermedad en las unidades de urgencias. A pesar de las importantes acciones iniciales para contener la enfermedad, aún existen debilidades en la capacitación de los recursos humanos, la vigilancia de la salud y la calidad de la detección de casos, que pueden impactar el control de la enfermedad y aumentar su infectividad, morbilidad y mortalidad futura.

HDAC5 enhances IRF3 activation and is targeted for degradation by protein C6 from orthopoxviruses including Monkeypox virus and Variola virus.

Histone deacetylases (HDACs) regulate gene expression and innate immunity. Previously, we showed that HDAC5 is degraded during Vaccinia virus (VACV) infection and is a restriction factor for VACV and herpes simplex virus type 1. Here, we report that HDAC5 promotes interferon regulatory factor 3 (IRF3) activation downstream of Toll-IL-1 receptor (TIR) domain-containing adaptor molecule-1 or Sendai virus-mediated stimulation without requiring HDAC activity. Loss of HDAC5-mediated IRF3 activation is restored by re-introduction of HDAC5 but not HDAC1 or HDAC4. The antiviral activity of HDAC5 is antagonized by VACV protein C6 and orthologs from the orthopoxviruses cowpox, rabbitpox, camelpox, monkeypox, and variola. Infection by many of these viruses induces proteasomal degradation of HDAC5, and expression of C6 alone can induce HDAC5 degradation. Mechanistically, C6 binds to the dimerization domain of HDAC5 and prevents homodimerization and heterodimerization with HDAC4. Overall, this study describes HDAC5 as a positive regulator of IRF3 activation and provides mechanistic insight into how the poxviral protein C6 binds to HDAC5 to antagonize its function.

Orally available nucleoside analog UMM-766 provides protection in a murine model of orthopox disease.

Although smallpox has been eradicated, other orthopoxviruses continue to be a public health concern as exemplified by the ongoing Mpox (formerly monkeypox) global outbreak. While medical countermeasures (MCMs) previously approved by the Food and Drug Administration for the treatment of smallpox have been adopted for Mpox, previously described vulnerabilities coupled with the questionable benefit of at least one of the therapeutics during the 2022 Mpox outbreak reinforce the need for identifying and developing other MCMs against orthopoxviruses. Here, we screened a panel of Merck proprietary small molecules and identified a novel nucleoside inhibitor with potent broad-spectrum antiviral activity against multiple orthopoxviruses. Efficacy testing of a 7-day dosing regimen of the orally administered nucleoside in a murine model of severe orthopoxvirus infection yielded a dose-dependent increase in survival. Treated animals had greatly reduced lesions in the lung and nasal cavity, particularly in the 10 µg/mL dosing group. Viral levels were also markedly lower in the UMM-766-treated animals. This work demonstrates that this nucleoside analog has anti-orthopoxvirus efficacy and can protect against severe disease in a murine orthopox model.IMPORTANCEThe recent monkeypox virus pandemic demonstrates that members of the orthopoxvirus, which also includes variola virus, which causes smallpox, remain a public health issue. While currently FDA-approved treatment options exist, risks that resistant strains of orthopoxviruses may arise are a great concern. Thus, continued exploration of anti-poxvirus treatments is warranted. Here, we developed a template for a high-throughput screening assay to identify anti-poxvirus small-molecule drugs. By screening available drug libraries, we identified a compound that inhibited orthopoxvirus replication in cell culture. We then showed that this drug can protect animals against severe disease. Our findings here support the use of existing drug libraries to identify orthopoxvirus-targeting drugs that may serve as human-safe products to thwart future outbreaks.

Orthopox viruses: is the threat growing?

BACKGROUND: Smallpox was a major cause of human mortality until its eradication, but the threat of orthopox viruses has not disappeared. Since the eradication of smallpox and the cessation of the related vaccination campaigns, the threat has been growing, as evidenced by the currently ongoing worldwide Mpox outbreak. In addition to threats of an evolving Mpox, we must also be aware of a myriad of other threats that remain. Many countries still lack biosecurity regulations reflecting the recent technological advances, and the threat of bioterrorism remains ever present. Reconstruction of smallpox is a distinct possibility, as are other scenarios whereby other orthopox viruses may be made more fit for transmission in humans. OBJECTIVES: To outline and discuss potential biosafety and biosecurity threats posed by orthopox viruses. SOURCES: Published scientific literature, news articles, and international agreements. CONTENT AND IMPLICATIONS: It would be wise to take steps to mitigate these threats now. Vaccination campaigns should be considered in areas with frequent orthopox outbreaks, and more efforts must be made to put a final end to the Mpox outbreak. In many countries, national biosafety and biosecurity regulations may need to be revised and strengthened to better reflect the threats posed by new technologies, including controls on synthesis of smallpox sequences. Furthermore, more international cooperation and aid is needed. The present global Mpox outbreak could likely have been prevented had areas where Mpox is endemic not been neglected. Future outbreaks could be much worse.

Genomic and transcriptomic analysis of the recent Mpox outbreak.

The Mpox (formerly named Monkeypox) virus is the etiological cause of a recent multi-country outbreak, with thousands of distinct cases detected outside the endemic areas of Africa as of December 2023. In this article, we analyze the sequences of full genomes of Mpox virus from Europe and compare them with all available Mpox sequences of historical relevance, annotated by year and geographic origin, as well as related Cowpox and Variola (smallpox) virus sequences. Our results show that the recent outbreak is most likely originating from the West African clade of Mpox, with >99 % sequence identity with sequences derived from historical and recent cases, dating from 1971 to 2017. We analyze specific mutations occurring in viral proteins between the current outbreak, previous Mpox and Cowpox sequences, and the historical Variola virus. Genome-wide sequence analysis of the recent outbreak and other Mpox/Cowpox/Variola viruses shows a very high conservation, with 97.9 % (protein-based) and 97.8 % (nucleotide-based) sequence identity. We identified significant correlation in human transcriptional responses as well, with a conserved immune pathway response induced in human cell cultures by the three families of Pox virus. The similarities identified between the major strains of Pox viruses, as well as within the Mpox clades, both at the genomic and transcriptomic levels, provide a molecular basis for the observed efficacy of Variola vaccines in other Poxviruses.

MPOX, o que sabemos sobre propagação e controle: uma revisão integrativa / MPOX, what we know about propagation and control: an integrative review / Viruela del mono, qué sabemos sobre la propagación y el control: una revisión integradora

Esta é uma revisão integrativa que busca compreender os fatores associados à propagação e controle de mpox, seguindo as recomendações estabelecidas pela declaração Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A consulta foi feita nas bases de dados PubMed, Lilacs e Cochrane Library. Foram selecionados quinze artigos, com amostra majoritária de homens que fazem sexo sem proteção com homens e homens que viajaram para locais com surto da doença ou tiveram contato com pessoas infectadas. Os principais fatores associados à infecção e à propagação da doença foram históricos de viagem, sexo desprotegido, ingestão de carne possivelmente contaminada, aglomerados e contato próximo com pessoa sintomática. Quanto aos fatores relacionados à prevenção, estão principalmente associados à triagem de casos suspeitos, hábitos de higiene pessoal, uso de equipamentos de proteção individual e isolamento do doente.

This integrative review examines the factors associated with mpox spread and control, following the recommendations established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Bibliographic search was conducted on the PubMed, Lilacs and Cochrane Library databases. The final sample included 15 articles, mostly composed of men who have unprotected sex with men and men who traveled to places with a mpox outbreak or had contact with infected people. Travel history, unprotected sex, eating potentially contaminated meat, crowding and close contact with a symptomatic person were the main factors associated with mpox infection and spread. Prevention is mainly associated with the screening of suspected cases, personal hygiene habits, use of personal protective equipment and patient isolation.

Este estudio realiza una revisión integradora para comprender los factores asociados con la propagación y el control de la viruela del mono, siguiendo las recomendaciones establecidas por Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Se consultaron las bases de datos PubMed, Lilacs y Cochrane Library. Se seleccionaron quince artículos, con una muestra mayoritaria de hombres que tienen sexo con hombres sin protección y hombres que viajaron a lugares con brote de la enfermedad o que tuvieron contacto con personas infectadas. Los principales factores asociados con la infección y la propagación de la enfermedad fueron el historial de viajes, las relaciones sexuales sin protección, el consumo de carne potencialmente contaminada, el hacinamiento y el contacto cercano con una persona sintomática. Los factores relacionados con la prevención están asociados principalmente con el tamizaje de casos sospechosos, los hábitos de higiene personal, el uso de equipos de protección personal y el aislamiento del paciente.

Modeling the Antiviral Activity of Ginkgo biloba Polyphenols against Variola: In Silico Exploration of Inhibitory Candidates for VarTMPK and HssTMPK Enzymes.

BACKGROUND: The aim of this study is to use modeling methods to estimate the antiviral activity of natural molecules extracted from Ginkgo biloba for the treatment of variola which is a zoonotic disease posing a growing threat to human survival. The recent spread of variola in nonendemic countries and the possibility of its use as a bioterrorism weapon have made it a global threat once again. Therefore, the search for new antiviral therapies with reduced side effects is necessary. METHODS: In this study, we examined the interactions between polyphenolic compounds from Ginkgo biloba, a plant known for its antiviral activity, and two enzymes involved in variola treatment, VarTMPK and HssTMPK, using molecular docking. RESULTS: The obtained docking scores showed that among the 152 selected polyphenolic compounds; many ligands had high inhibitory potential according to the energy affinity. By considering Lipinski's rules, we found that Liquiritin and Olivil molecules are the best candidates to be developed into drugs that inhibit VarTMPK because of their high obtained scores compared to reference ligands, and zero violations of Lipinski's rules. We also found that ginkgolic acids have good affinities with HssTMPK and acceptable physicochemical properties to be developed into drugs administered orally. CONCLUSION: Based on the obtained scores and Lipinski's rules, Liquiritin, Olivil, and ginkgolic acids molecules showed interesting results for both studied enzymes, indicating the existence of promising and moderate activity of these polyphenols for the treatment of variola and for possible multi-targeting. Liquiritin has been shown to exhibit anti-inflammatory effects on various inflammation- related diseases such as skin injury, hepatic inflammatory injury, and rheumatoid arthritis. Olivil has been shown to have antioxidant activity. Olivil derivatives have also been studied for their potential use as anticancer agents. Ginkgolic acids have been shown to have antimicrobial and antifungal properties. However, ginkgolic acids are also known to cause allergic reactions in some people. Therefore, future studies should consider these results and explore the potential of these compounds as antiviral agents. Further experimental studies in-vitro and in-vivo are required to validate and scale up these findings.

Variola Virus and Clade I Mpox Virus Differentially Modulate Cellular Responses Longitudinally in Monocytes During Infection.

Variola virus (VARV), the etiological agent of smallpox, had enormous impacts on global health prior to its eradication. In the absence of global vaccination programs, mpox virus (MPXV) has become a growing public health threat that includes endemic and nonendemic regions across the globe. While human mpox resembles smallpox in clinical presentation, there are considerable knowledge gaps regarding conserved molecular pathogenesis between these 2 orthopoxviruses. Thus, we sought to compare MPXV and VARV infections in human monocytes through kinome analysis. We performed a longitudinal analysis of host cellular responses to VARV infection in human monocytes as well as a comparative analysis to clade I MPXV-mediated responses. While both viruses elicited strong activation of cell responses early during infection as compared to later time points, several key differences in cell signaling events were identified and validated. These observations will help in the design and development of panorthopoxvirus therapeutics.

"Valha-nos a Providência!": festas e ritos católicos em tempos epidêmicos, Salvador-BA, Brasil, 1918-1919 / "God for us!": Catholic festivals and rites in times of epidemics, Salvador-BA, Brasil, 1918-1919

Resumo O artigo analisa as reações dos católicos vinculados às associações leigas na cidade do Salvador, no período da gripe espanhola (1918) e da varíola (1919). Os jornais foram as principais fontes utilizadas para a identificação das festas e dos ritos, tanto dos praticados para pedir a intercessão dos santos quanto daqueles que foram suspensos em função da necessidade de isolamento social. Apesar de ambas as doenças serem transmissíveis e do curto espaço de tempo entre as duas epidemias, a análise das fontes evidenciou diferentes reações dos fiéis quanto às medidas de proteção e busca da cura.

Abstract This article analyzes the reactions of Catholics linked to lay associations in the city of Salvador, in the period of the Spanish flu (1918) and smallpox (1919). Newspapers were the main sources used to identify the festivals and rites, both those practiced to ask for the intercession of the saints, and those that were suspended due to the need for social isolation. In spite of both diseases being transmissible and the short interval between the two epidemics, the analysis of the sources showed different reactions from the faithful regarding the measures of protection and the search for a cure.

Guidance for the identification of bony lesions related to smallpox.

OBJECTIVE: This research aimed to address the underrepresentation of smallpox (osteomyelitis variolosa) in palaeopathology, providing a synthesis of published literature and presenting guidance for the identification of osteomyelitis variolosa in non-adult and adult skeletal remains. MATERIALS AND METHODS: Literature regarding smallpox and published reports of individuals with osteomyelitis variolosa were synthesised and critiqued to produce clear diagnostic criteria for the identification of smallpox osteologically. RESULTS: Associated osteological changes begin in non-adults, where skeletal morphology is rapidly changing. Characteristic lesions associated with non-adult osteomyelitis variolosa include inflammation and destructive remodelling of long-bone joints and metaphyses. Where childhood infection was survived, residual osteomyelitis variolosa lesions should also be visible in adults in the osteoarchaeological record. CONCLUSIONS: Despite long-term clinical recognition, only limited osteological and archaeological evidence of osteomyelitis variolosa has yet emerged. With improved diagnostic criteria, osteomyelitis variolosa may be more frequently identified. SIGNIFICANCE: This is the first synthesis of osteomyelitis variolosa encompassing both clinical and palaeopathological literature, providing detailed guidance for the identification of osteomyelitis variolosa in skeletal remains. It will lead to the increased identification of smallpox osteologically. LIMITATIONS: Differential diagnoses should always be considered. The archaeological longevity of smallpox, and the potential for archaeological VARV to cause clinically recognised smallpox, is currently unknown. Characteristic bone changes in the archaeological record may be other, extinct human-infecting-orthopoxviruses. SUGGESTIONS FOR FURTHER RESEARCH: Further consideration of the implications of age of smallpox contraction on bony pathology: whether epiphyses are affected differently due to state of fusion. Reassessment of individuals previously identified with smallpox-consistent lesions, but otherwise diagnosed.

Functional epitopes and neutralizing antibodies of vaccinia virus.

Smallpox is an infectious disease caused by the variola virus, and it has a high mortality rate. Historically it has broken out in many countries and it was a great threat to human health. Smallpox was declared eradicated in 1980, and Many countries stopped nation-wide smallpox vaccinations at that time. In recent years the potential threat of bioterrorism using smallpox has led to resumed research on the treatment and prevention of smallpox. Effective ways of preventing and treating smallpox infection have been reported, including vaccination, chemical drugs, neutralizing antibodies, and clinical symptomatic therapies. Antibody treatments include anti-sera, murine monoclonal antibodies, and engineered humanized or human antibodies. Engineered antibodies are homologous, safe, and effective. The development of humanized and genetically engineered antibodies against variola virus via molecular biology and bioinformatics is therefore a potentially fruitful prospect with respect to field application. Natural smallpox virus is inaccessible, therefore most research about prevention and/or treatment of smallpox were done using vaccinia virus, which is much safer and highly homologous to smallpox. Herein we summarize vaccinia virus epitope information reported to date, and discuss neutralizing antibodies with potential value for field application.

Gene duplication, gene loss, and recombination events with variola virus shaped the complex evolutionary path of historical American horsepox-based smallpox vaccines.

IMPORTANCE: Modern smallpox vaccines, such as those used against mpox, are made from vaccinia viruses, but it is still unknown whether cowpox, horsepox, or vaccinia viruses were used in the early 20th century or earlier. The mystery began to be solved when the genomes of six historical smallpox vaccines used in the United States from 1850 to 1902 were determined. Our work analyzed in detail the genomes of these six historical vaccines, revealing a complex genomic structure. Historical vaccines are highly similar to horsepox in the core of their genomes, but some are closer to the structure of vaccinia virus at the ends of the genome. One of the vaccines is a recombinant virus with parts of variola virus recombined into its genome. Our data add valuable information for understanding the evolutionary path of current smallpox vaccines and the genetic makeup of the potentially extinct group of horsepox viruses.

Mpox: Aspectos epidemiológicos, imunopatogênicos e manejo pré e pós-infecção / Mpox: Epidemiological, immunopathogenic aspects and pre- and post-infection management

Mpoxou Varíola M é uma zoonose causada por vírus do gênero Orthopoxvirus, causadores também da varíola comum. É uma doença considerada rara e autolimitada, sendo endêmica em países africanos. Entretanto, no ano de 2022 ganhou destaque devido ao surto global que se iniciou, quando o mundo ainda se recuperava da pandemia da COVID-19. Dessa forma, por se tratar de uma doença emergente, a presente revisão visa pontuar aspectos gerais do que se sabe até o momento sobre a Mpox, desde sua imunopatogenia até as formas atuais de prevenção e cuidados pós-infecção

Mpox or Variola M is a zoonosis caused by viruses of the genus Orthopoxvirus, which also cause smallpox. It is a disease considered rare and self-limiting, being endemic in African countries. However, in 2022, it gained prominence due to the global outbreak that began when the world was still recovering from the COVID-19 pandemic. Thus, as it is an emerging disease, this review aims to point out general aspects of what is known so far about Mpox, from its immunopathogenesis to current forms of prevention and post-infection care

La viruela símica, alcances sobre lo que se conoce / Monkeypox, insights into what is known / Monkeypox, escopo do que é conhecido

La viruela símica es una enfermedad zoonótica endémica de África occidental y central, pero el actual brote está presentado una inusual propagación por el mundo a pesar de su limitada capacidad para trasmitirse de humano a humano, situación que ha generado una preocupación sanitaria a nivel mundial. Objetivo. Identificar la viruela símica, descripción del monkeypox virus, brote actual de la viruela símica, etiología, trasmisión, signos y síntomas, diagnóstico, vacunación y tratamiento antiviral. Metodología. Se llevó a cabo una revisión sistemática en PubMed, Ovid y LILACS, empleando operadores booleanos como, "monkeypox" OR "MPXV" OR "human monkeypox" OR "virus monkeypox", en total se identificaron 986 registros, en inglés y español. La fase de cribado recabo 59 registros entre artículos científicos y literatura gris publicados entre el 2010 y el 2022. El proceso de revisión se desarrolló bajo los estándares del método PRISMA; la elegibilidad, incluyó valoración de la calidad científica por listas de comprobación, y la inclusión contempló los criterios de calidad de la evidencia y graduación de la fuerza de recomendación. Resultados. Se encontraron 287 registros en PubMed, 699 en Ovid Medline®, se localizaron en total 986 registros electrónicos. Conclusión. El incremento de la trasmisión de humano a humano pone en peligro al entorno familiar y a quienes brindan el cuidado de salud. Las erupciones cutáneas son el signo patognomónico durante la valoración clínica. La inmunidad colectiva alcanzada durante la vacunación contra la viruela humana se ha reducido, contribuyendo en el aumento de casos y la propagación.

Smallpox is a zoonotic disease endemic to West and Central Africa, but the current outbreak is showing an unusual spread throughout the world despite its limited ability to transmit from human to human, a situation that has raised global health concern. Objective. To identify monkeypox, description of monkeypox virus, current outbreak of monkeypox, etiology, transmission, signs and symptoms, diagnosis, vaccination and antiviral treatment. Methodology. A systematic review was carried out in PubMed, Ovid and LILACS, using Boolean operators such as, "monkeypox" OR "MPXV" OR "human monkeypox" OR "monkeypox virus", a total of 986 records were identified, in English and Spanish. The screening phase collected 59 records between scientific articles and grey literature published between 2010 and 2022. The review process was developed under the standards of the PRISMA method; eligibility included assessment of scientific quality by checklists, and inclusion contemplated the criteria of quality of evidence and grading of the strength of recommendation. Results. A total of 287 records were found in PubMed, 699 in Ovid Medline®, and 986 electronic records were located. Conclusion. The increase in human-to-human transmission endangers the family environment and health care providers. Skin rashes are the pathognomonic sign during clinical assessment. The herd immunity achieved during human smallpox vaccination has been reduced, contributing to the increase in cases and spread.

A varíola é uma doença zoonótica endêmica da África Ocidental e Central, mas o surto atual está mostrando uma disseminação global incomum, apesar de sua capacidade limitada de transmissão de pessoa para pessoa, uma situação que levantou preocupações com a saúde global. Objetivo. Identificar a varíola do macaco, a descrição do vírus da varíola do macaco, o atual surto de varíola do macaco, a etiologia, a transmissão, os sinais e sintomas, o diagnóstico, a vacinação e o tratamento antiviral. Metodologia. Foi realizada uma revisão sistemática no PubMed, Ovid e LILACS, usando operadores booleanos como "monkeypox" OR "MPXV" OR "human monkeypox" OR "monkeypox virus", no total foram identificados 986 registros, em inglês e espanhol. A fase de triagem coletou 59 registros de artigos científicos e literatura cinzenta publicados entre 2010 e 2022. O processo de revisão foi desenvolvido de acordo com os padrões do método PRISMA; a elegibilidade incluiu a avaliação da qualidade científica por meio de listas de verificação, e a inclusão contemplou os critérios de qualidade de evidência e graduação da força de recomendação. Resultados. Foram encontrados 287 registros no PubMed, 699 no Ovid Medline® e um total de 986 registros eletrônicos. Conclusões. O aumento da transmissão de pessoa para pessoa coloca em risco o ambiente doméstico e os prestadores de serviços de saúde. Erupções cutâneas são o sinal patognomônico durante a avaliação clínica. A imunidade de rebanho obtida durante a vacinação contra a varíola humana foi reduzida, contribuindo para o aumento dos casos e da disseminação.