[Clinicopathological study of 24 cases of monkeypox virus infection-related rashes].

Objective: To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests. Methods: Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope® hybridization and electron microscopy. Results: All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri's bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope® hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions: The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

Mpox infection of stromal cells and macrophages of macaque with endometriosis.

The mpox outbreak of 2022-2023 represented a new global health challenge and recognition of mpox as a sexually transmitted disease. The majority of cases were reported in men who have sex with men (MSM), but women are also susceptible, especially during pregnancy. We evaluated the reproductive tracts of a subset of macaques from a large rechallenge study of mpox infection with virus from the 2022 outbreak and identified intraabdominal mpox replication associated with endometriosis. Mpox virus (MPXV) was found not only in skin, but in the cervix, the uterus, and periovarian endometriotic lesions of the affected macaque. Mpox replication preferentially targeted vimentin-positive poorly differentiated endometriotic stromal tissue and infiltrating macrophages in the reproductive tract. Mpox tropism for stromal cells and macrophages has broad implications for mpox pathogenesis and associated clinical syndromes. In addition, women with endometriosis may be at heightened risk for adverse outcomes associated with mpox infection. The rhesus macaque provides rare insight into this disease and the potential complications of mpox infection in the context of genitourinary tract disease.

Histopathologic Findings of Evolving Mpox Lesions.

ABSTRACT: This article reports two cases of the 2022 mpox virus with notable histopathology, and includes a novel description of mpox pseudotumor in the perianal region which is not previously described. This article additionally includes literature review of characteristic histopathology through evolving lesions, as it is sparsely described in relation to the 2022 mpox outbreak. Case one describes a 42-year-old man who presented with umbilicated, smooth papules on the trunk and extremities, and milia-like papules on the face. Histopathology of an umbilicated lesion revealed epidermal acanthosis with keratinocyte pallor, ballooning degeneration, keratinocyte necrosis, and neutrophilic epitheliotropism. Case two describes a 51-year-old man who presented with scattered eroded papules as well as a perianal mass. Histopathology of the mass revealed ulceration with keratinocyte enlargement and pallor with a mixed inflammatory cell infiltrate. It additionally revealed rare multinucleated keratinocytes with nuclear molding. These cases are remarkable and contribute to literature as reports of the histopathology of the atypical 2022 mpox outbreak are rare. A combination of clinical, laboratory, and histopathologic evidence is useful in diagnosing mpox, and these cases contribute to describing the evolution of viral lesions.

Inefficient tissue immune response against MPXV in an immunocompromised mpox patient.

The recent outbreak of monkeypox virus (MPXV) was unprecedented in its size and distribution. Those living with uncontrolled HIV and low CD4 T cell counts might develop a fulminant clinical mpox course with increased mortality, secondary infections, and necrotizing lesions. Fatal cases display a high and widespread MPXV tissue burden. The underlying pathomechanisms are not fully understood. We report here the pathological findings of an MPXV-driven abscess in gastrocnemius muscle requiring surgery in an immunocompromised patient with severe mpox. Presence of virus particles and infectivity were confirmed by electron microscopy, expansion microscopy, and virus culture, respectively. MPXV tissue distribution by immunohistochemistry (IHC) showed a necrotic core with infection of different cell types. In contrast, at the lesion rim fibroblasts were mainly infected. Immune cells were almost absent in the necrotic core, but were abundant at the infection rim and predominantly macrophages. Further, we detected high amounts of alternatively activated GPNMB+-macrophages at the lesion border. Of note, macrophages only rarely colocalized with virus-infected cells. Insufficient clearance of infected cells and infection of lesion-associated fibroblasts sustained by the abundance of profibrotic macrophages might lead to the coalescing of lesions and the severe and persistent clinical mpox course observed in immunocompromised patients.

An atypical presentation of human monkeypox infection with clinicopathologic correlation.

There is growing evidence to support new modes of transmission for human monkeypox infection. As these methods are being explored, this report delineates the day-to-day clinical sequelae following the initial exposure in an HIV-positive man who had sexual intercourse with another man days preceding his infection. We describe atypical cutaneous manifestations involving widespread erythematous pustules with preceding anogenital ulcerations and concomitant bilateral inguinal lymphadenopathy. Clinicopathologic correlation is used to assist in the workup and establishing the diagnosis. Our case supports others reported in the literature that suggest sexual contact as a means of transmission. More research is needed that investigates the presence of infection in both men and women, including those who could act as carriers, to elucidate other pathways in this evolving yet evasive viral disease.

Human monkeypox disease prediction using novel modified restricted Boltzmann machine-based equilibrium optimizer.

While the globe continues to struggle to recover from the devastation brought on by the COVID-19 virus's extensive distribution, the recent worrying rise in human monkeypox outbreaks in several nations raises the possibility of a novel worldwide pandemic. The symptoms of human monkeypox resemble those of chickenpox and traditional measles, with a few subtle variations like the various kinds of skin blisters. A range of deep learning techniques have demonstrated encouraging results in image-oriented tumor cell, Covid-19 diagnosis, and skin disease prediction tasks. Hence, it becomes necessary to perform the prediction of the new monkeypox disease using deep learning techniques. In this paper, an image-oriented human monkeypox disease prediction is performed with the help of novel deep learning methodology. Initially, the data is gathered from the standard benchmark dataset called Monkeypox Skin Lesion Dataset. From the collected data, the pre-processing is accomplished using image resizing and image normalization as well as data augmentation techniques. These pre-processed images undergo the feature extraction that is performed by the Convolutional Block Attention Module (CBAM) approach. The extracted features undergo the final prediction phase using the Modified Restricted Boltzmann Machine (MRBM), where the parameter tuning in RBM is accomplished by the nature inspired optimization algorithm referred to as Equilibrium Optimizer (EO), with the consideration of error minimization as the major objective function. Simulation findings demonstrate that the proposed model performed better than the remaining models at monkeypox prediction. The proposed MRBM-EO for the suggested human monkeypox disease prediction model in terms of RMSE is 75.68%, 70%, 60.87%, and 43.75% better than PSO-SVM, Xception-CBAM-Dense, ShuffleNet, and RBM respectively. Similarly, the proposed MRBM-EO for the suggested human monkeypox disease prediction model with respect to accuracy is 9.22%, 7.75%, 3.77%, and 10.90% better than PSO-SVM, Xception-CBAM-Dense, ShuffleNet, and RBM respectively.

Tracing the footprints of MPXV in Asia: phylogenetic insights and lineage dynamics.

OBJECTIVES: The 2022 global outbreak of monkeypox virus (MPXV), previously confined to Central and West Africa, necessitates an enhanced understanding of its spread. Comprehensive genomic surveillance to understand the virus's evolution and spread is needed, particularly in Asia. METHODS: Genomic data from 169 MPXV genome sequences in Asia were analysed. Through advanced genomic sequencing of clinical samples, we analysed the distribution and mutations of MPXV lineages in Asia. RESULTS: Phylogenetic analysis revealed a distinct clustering of C.1 strains rise in Northeast Asia in 2023, while genomic examination identified specific consensus mutations like R84K, R665C and L16F in C.1 strains. The mutations, coupled with an increased rate of apolipoprotein B mRNA-editing catalytic polypeptide-like 3 motif G-to-A mutations in C.1 (OR 24.87±8.81), indicate a potential adaptation mechanism. CONCLUSIONS: Our findings underscore the need for ongoing surveillance and provide vital insights into MPXV's evolving dynamics, aiding in public health strategy formulation against this emerging infectious threat.

Knowledge about, attitudes toward and acceptance and predictors of intention to receive the mpox vaccine among cancer patients in China: A cross-sectional survey.

This study aimed to investigate the knowledge about, attitudes toward, and acceptance and predictors of receiving the mpox vaccine among Chinese cancer patients. Patients were selected using a convenience sampling method. A web-based self-report questionnaire was developed to assess cancer patients' knowledge, attitudes, and acceptance regarding the mpox vaccine. Multivariate logistic regression analysis was used to determine predictors of acceptance of the mpox vaccine. A total of 805 cancer patients were included in this study, with a vaccine hesitancy rate of 27.08%. Approximately 66% of the patients' information about mpox and the vaccine came from the mass media, and there was a significant bias in the hesitant group's knowledge about mpox and the vaccine. Multivariable logistic regression analysis suggested that retirement; chemotherapy; the belief that the mpox vaccine could prevent disease, that vaccination should be compulsory when appropriate and that the mpox vaccine prevents mpox and reduces complications; the willingness to pay for the mpox vaccine; the willingness to recommend that friends and family receive the mpox vaccine; and the belief that the mpox vaccine should be distributed fairly and equitably were factors that promoted vaccination. The belief that mpox worsens tumor prognosis was a driving factor for vaccine hesitancy. This study investigated the knowledge of cancer patients about mpox and the vaccine, evaluated the acceptance and hesitancy rates of the mpox vaccine and examined the predictors of vaccination intention. We suggest that the government scientifically promote the vaccine and develop policies such as free vaccination and personalized vaccination to increase the awareness and acceptance rate of the mpox vaccine.

Notified cases of mpox in the city of Rio de Janeiro, Brazil: a descriptive study, 2022.

OBJECTIVE: To describe the profile of cases of mpox in the city of Rio de Janeiro between June and November 2022. METHODS: This was a descriptive study of secondary data obtained from mpox notification forms. Socioeconomic, clinical and spatial data were analyzed. RESULTS: Of the 928 cases, 93.7% were male, 85.0% cisgender male, 65.6% homosexual, 41.8% between 30 and 39 years old, and 41.0% were of White race/skin color. A total of 34.5% had immunosuppression due to illness, and 41.9% reported their HIV status as being positive. The most prevalent signs and symptoms were: skin lesions (96.6%), especially with multiple manifestations (67.8%) in the genital region (46.1%), in addition to fever (58.3%), adenomegaly (43.3%) and headache (38.7%). Most notifications occurred in public services (81.3%) and in hospital care (51.3%). CONCLUSION: The study revealed high incidence of mpox, especially among young, cisgender and homosexual men. Most cases were mild, with genital lesions, progressing to cure without hospitalization. Person-to-person transmission was predominant.

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.

Incidental diagnosis of mpox virus infection in patients undergoing sexually transmitted infection screening-findings from a study in France.

OBJECTIVES: This study aimed to investigate the prevalence of mpox virus (MPXV) infections in the general population consulting for routine sexually transmitted infections (STIs) in our Marseille public hospital. In fact, the recent worldwide MPXV outbreak mainly impacted men who have sex with men and the prevalence of MPXV infections in the general population remains poorly defined. METHODS: All samples addressed routinely to our microbiological laboratory for STIs between July 1 and October 15, 2022 were screened with MPXV-specific quantitative polymerase chain reaction. RESULTS: A total of 2688 samples from 1896 patients suspected of having STIs were tested and eight (0.4%) patients were incidentally diagnosed with MPXV infection, including six men and two women. MPXV was detected in rectal swabs (n = 2), urine (n = 2), vaginal swabs (n = 2), a urethral swab (n = 1), and a skin swab (n = 1). CONCLUSIONS: This study suggests that some MPXV infections are likely to be underdiagnosed because of their non-specific clinical presentation and/or insufficient clinical knowledge of the disease. Our data showed that systematic screening was particularly useful for detecting MPXV in patients without classic lesions or cases of asymptomatic carriage in patients reporting recent high-risk exposure and in patients presenting no obvious risk factor.

Mpox Case Presenting With Genital Lesions and Proctitis.

ABSTRACT: Monkeypox (Mpox) is a zoonotic Orthopoxvirus of the Poxviridae family, endemic to Africa. In August 2022, the US government declared it an emergency because of the worldwide spread. Traditionally, Mpox infection spreads through contact with infected animals. However, the 2022 outbreak Centers for Disease Control and Prevention (CDC) data note that 94% of cases had recent male-to-male sexual or close intimate contact, suggesting a novel sexual transmission. In this article, we report a 39-year-old HIV-positive man presenting with a diffuse cutaneous rash, perianal pain, and bloody stool of 2-week duration. A medical history includes intravenous drug use and multiple sexual partners. Physical examination revealed umbilicated, tan-colored, crusted cutaneous papules scattered across the face, trunk, and genital regions. Perianal lesion biopsy showed an acanthotic epidermis with spongiosis, ballooning degeneration of keratinocytes, and the formation of multinucleated syncytial keratinocytes. A dermal superficial/lichenoid mixed inflammatory cell infiltrate with multinucleated giant cells was noted. Perianal lesion polymerase chain reaction (PCR) was positive for Mpox. Colonoscopy revealed a 3-cm circumferential rectal ulcer with gray exudate and necrosis. A rectal ulcer biopsy showed an ulcerated mucosa with acute proctitis and necrosis. There were scattered macrophages with intranuclear inclusion and glassy vacuolization, and Mpox infection was confirmed by immunostaining with a Mpox-specific anti-Vaccinia virus antibody.

Monkeypox virus infection of human astrocytes causes gasdermin B cleavage and pyroptosis.

Monkeypox virus (MPXV) infections in humans cause neurological disorders while studies of MPXV-infected animals indicate that the virus penetrates the brain. Pyroptosis is an inflammatory type of regulated cell death, resulting from plasma membrane rupture (PMR) due to oligomerization of cleaved gasdermins to cause membrane pore formation. Herein, we investigated the human neural cell tropism of MPXV compared to another orthopoxvirus, vaccinia virus (VACV), as well as its effects on immune responses and cell death. Astrocytes were most permissive to MPXV (and VACV) infections, followed by microglia and oligodendrocytes, with minimal infection of neurons based on plaque assays. Aberrant morphological changes were evident in MPXV-infected astrocytes that were accompanied with viral protein (I3) immunolabelling and detection of over 125 MPXV-encoded proteins in cell lysates by mass spectrometry. MPXV- and VACV-infected astrocytes showed increased expression of immune gene transcripts (IL12, IRF3, IL1B, TNFA, CASP1, and GSDMB). However, MPXV infection of astrocytes specifically induced proteolytic cleavage of gasdermin B (GSDMB) (50 kDa), evident by the appearance of cleaved N-terminal-GSDMB (30 kDa) and C-terminal- GSDMB (18 kDa) fragments. GSDMB cleavage was associated with release of lactate dehydrogenase and increased cellular nucleic acid staining, indicative of PMR. Pre-treatment with dimethyl fumarate reduced cleavage of GSDMB and associated PMR in MPXV-infected astrocytes. Human astrocytes support productive MPXV infection, resulting in inflammatory gene induction with accompanying GSDMB-mediated pyroptosis. These findings clarify the recently recognized neuropathogenic effects of MPXV in humans while also offering potential therapeutic options.

Clinical and Epidemiological Characteristics of Mpox in HIV-Infected and Uninfected Men Who Have Sex with Men: A Retrospective Study in Lisbon.

The resurgence of Mpox, predominantly among men who have sex with men (MSM), has prompted an analysis of its clinical manifestations and epidemiological patterns, particularly in individuals living with human immunodeficiency virus (HIV). This retrospective study aims to delineate and compare the clinical presentations and epidemiological characteristics of Mpox among HIV-positive and HIV-negative individuals. A total of 58 confirmed Mpox cases from a dermatology department in Lisbon were analyzed, focusing on mucocutaneous manifestations, systemic symptoms, and laboratory parameters. Our findings indicate no significant difference in disease severity and presentation between HIV-positive and HIV-negative groups, suggesting that HIV status may not be a determinant of Mpox severity, but rather an indicator of increased sexual risk behaviors, a recognized risk factor for Mpox transmission.

Caso probable de síndrome de reconstitución inmune por mpox en una persona con inmunosupresión avanzada por VIH / Probable case of mpox immune reconstitution inflammatory syndrome (IRIS) in a person with HIV disease

Se presenta el caso clínico de persona viviendo con VIH, con mala adherencia a tratamiento, sin vacunación previa para mpox, que evolucionó con un cuadro clínico probable de síndrome de reconstitución inmune posterior a reinicio de TAR, debido a la progresión de las lesiones cutáneas. Recibió tratamiento con tecovirimat por siete días, con evolución clínica favorable. Corresponde al primer caso reportado que recibió terapia con tecovirimat en Chile.

We report a clinical case of a person living with HIV with poor adherence to treatment, no previous mpox vaccination, who had a probable mpox syndrome immune reconstitution after restarting ART, due to worsening of skin lesions. He received treatment with tecovirimat for 7 days, clinically improved and was discharged in good condition. We reported this first clinical case that received tecovirimat in Chile.