Analysis of Monkeypox Virus Exposures and Lesions by Anatomic Site.

We used cross-sectional data from 226 patients with monkeypox virus to investigate the association between anatomic exposure site and lesion development. Penile, anorectal, and oral exposures predicted lesion presence at correlating anatomic sites. Exposure site also predicted the first lesion site of the penis and anus.

Mpox and Lessons Learned in the Light of the Recent Outbreak: A Narrative Review.

According to the WHO, more than 90,000 cases of mpox have been reported since the 2022 worldwide outbreak, which resulted in 167 deaths, while a new outbreak in Africa since 2023 has resulted in over 18,000 cases and 617 deaths. Mpox is a zoonosis caused by the monkeypox virus, a double-stranded DNA virus belonging to the Orthopoxvirus genus, which causes smallpox-like illness. Until 2022, cases were predominately located in West and Central Africa, with only sporadic cases and outbreaks reported in other parts of the world. During the 2022 outbreak, the primary mode of transmission was sexual contact among men who have sex with men. The changing epidemiology of mpox resulted in new disease phenotypes and populations at risk, disproportionally affecting people who live with HIV. Commonly presenting as a mild, self-limiting illness, mpox can cause severe and protracted disease in people with HIV with a CD4 count < 200 cell/mm3. The global emergence of mpox that followed and intersected with COVID-19 mobilized the scientific community and healthcare stakeholders to provide accurate diagnostics, preventive vaccines and treatment to those most affected. Despite existing gaps, this rapid response helped to contain the outbreak, but challenges remain as new variants emerge. Preparedness and readiness to respond to the next outbreak is crucial in order to minimize the impact to the most vulnerable.

[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.

Epidemiological analysis of confirmed mpox cases, Burundi, 3 July to 9 September 2024.

We analysed mpox cases in Burundi from July to September 2024, following the introduction of Clade Ib virus. Of 607 samples from the whole population of suspected cases, 154 were PCR-positive, of whom 85 were children under 15 years, with a higher proportion of female children testing positive. Geographical analysis demonstrates case concentration in Bujumbura Mairie (91/154). Age- and sex-specific interventions, as well as community engagement, are important for outbreak containment, as are targeted public health strategies in Burundi.

Monkeypox Clade Ib virus introduction into Burundi: first findings, July to mid-August 2024.

We describe cases with monkeypox virus (MPXV) Clade Ib in Burundi from their first detection in July until 20 August 2024. Testing 442 people with vesicular lesions confirmed 170 cases (98 male; 72 female), 82 (48%) being < 15 years old. Differential diagnosis of the first 30 individuals testing MPXV negative revealed chickenpox in 20. Cases occurred in 26 of 49 Burundi health districts, but mostly in Bujumbura Nord (88/170; 67%). Case-derived MPXV genetic sequences from Burundi and South-Kivu (Democratic Republic of the Congo), clustered together in phylogenetic analysis.

Diagnostic and surveillance testing capability for mpox in the EU/EEA, September 2024.

In response to the increasing number of mpox cases caused by monkeypox virus (MPXV) clade I in the African continent and the first reported travel-related clade Ib case of mpox in EU/EEA, the European Centre for Disease Prevention and Control surveyed national capability for detection and characterisation of MPXV in the EU/EEA. The results showed high level of capability for case confirmation by PCR, alongside molecular typing methods for identification of MPXV clades and/or clade I subclades within the EU/EEA.

Viral genetics and transmission dynamics in the second wave of mpox outbreak in Portugal and forecasting public health scenarios.

In 2023, a second wave of the global mpox epidemic, which is mainly affecting men who have sex with men (MSM), was observed in some countries. Herein, we benefited from a large viral sequence sampling (76/121; 63%) and vast epidemiological data to characterise the re-emergence and circulation of the Monkeypox virus (MPXV) in Portugal during 2023. We also modelled transmission and forecasted public health scenarios through a compartmental susceptible-exposed-infectious-recovered (SEIR) model. Our results suggest that the 2023 mpox wave in Portugal resulted from limited introduction(s) of MPXV belonging to C.1.1 sublineage, hypothetically from Asia, followed by sustained viral transmission and potential exportation to other countries. We estimated that the contribution of the MSM high sexual activity group to mpox transmission was 120 (95% CrI: 30-3553) times higher than that of the low sexual activity group. However, among the high sexual activity group, vaccinated individuals likely contributed approximately eight times less [0.123 (95% CrI: 0.068-0.208)] than the unvaccinated ones. Vaccination was also linked to potential reduced disease severity, with a Mpox Severity Score of 6.0 in the vaccinated group compared to 7.0 in unvaccinated individuals. Scenario analysis indicated that transmission is highly sensitive to sexual behaviour, projecting that a slight increase in the MSM sub-population with high sexual activity can trigger new mpox waves. This study strongly supports that continued vaccination, targeted awareness among risk groups and routine genomic epidemiology is needed to anticipate and respond to novel MPXV threats (e.g. global dissemination of clade I viruses).

Antivirals for monkeypox virus: Proposing an effective machine/deep learning framework.

Monkeypox (MPXV) is one of the infectious viruses which caused morbidity and mortality problems in these years. Despite its danger to public health, there is no approved drug to stand and handle MPXV. On the other hand, drug repurposing is a promising screening method for the low-cost introduction of approved drugs for emerging diseases and viruses which utilizes computational methods. Therefore, drug repurposing is a promising approach to suggesting approved drugs for the MPXV. This paper proposes a computational framework for MPXV antiviral prediction. To do this, we have generated a new virus-antiviral dataset. Moreover, we applied several machine learning and one deep learning method for virus-antiviral prediction. The suggested drugs by the learning methods have been investigated using docking studies. The target protein structure is modeled using homology modeling and, then, refined and validated. To the best of our knowledge, this work is the first work to study deep learning methods for the prediction of MPXV antivirals. The screening results confirm that Tilorone, Valacyclovir, Ribavirin, Favipiravir, and Baloxavir marboxil are effective drugs for MPXV treatment.

Identification of mpox M1R and B6R monoclonal and bispecific antibodies that efficiently neutralize authentic mpox virus.

In 2022, the monkeypox virus (mpox virus, MPXV) exhibited global dissemination across six continents, representing a notable challenge owing to the scarcity of targeted antiviral interventions. Passive immunotherapy, such as the use of monoclonal antibodies (mAbs) and bispecific antibodies (bsAbs), has emerged as a promising option for antiviral regimens. Here, we generated several mAbs against M1R and B6R of MPXV, and subsequently characterized the antiviral activity of these antibodies both in vitro and in vivo. Two neutralizing mAbs, M1H11 and M3B2, targeting M1R, and one B6R-specific mAb, B7C9, were identified. They exhibited varying antiviral efficacy against vaccinia virus (VACV) in vitro and in vivo. A cocktail comprising M1H11 and M3B2 demonstrated a superior protective effect in vivo. A bsAb, Bis-M1M3, was engineered by conjugating the fragment crystallizable (Fc) region of the human-mouse chimeric engineered M1H11 with the single-chain fragment variable (scFv) of M3B2. In mice challenged with MPXV, Bis-M1M3 showed a notable protective effects. Analysis of neutralization mechanism showed that these mAbs and Bis-M1M3 exerted virus-neutralizing effects before the virus infects cells. In vivo pharmacokinetic experiments showed that Bis-M1M3 has a long half-life in rhesus macaques. This study provides crucial insights for further research on broad-spectrum antiviral drugs against MPXV and other orthopoxviruses.

Epidemiologic Quantities for Monkeypox Virus Clade I from Historical Data with Implications for Current Outbreaks, Democratic Republic of the Congo.

We used published data from outbreak investigations of monkeypox virus clade I in the Democratic Republic of the Congo to estimate the distributions of critical epidemiological parameters. We estimated a mean incubation period of 9.9 days (95% credible interval [CrI] 8.5-11.5 days) and a mean generation time of 17.2 days (95% CrI 14.1-20.9 days) or 11.3 days (95% CrI 9.4-14.0 days), depending on the considered dataset. Presymptomatic transmission was limited. Those estimates suggest generally slower transmission dynamics in clade I than in clade IIb. The time-varying reproduction number for clade I in the Democratic Republic of the Congo was estimated to be below the epidemic threshold in the first half of 2024. However, in the South Kivu Province, where the newly identified subclade Ib has been associated with sustained human-to-human transmission, we estimated an effective reproduction number above the epidemic threshold (95% CrI 0.96-1.27).

A novel isothermal whole genome sequencing approach for Monkeypox Virus.

Monkeypox virus (MPXV) is the zoonotic agent responsible for mpox, an often-self-limiting pox-like disease. Since May 2022, an outbreak characterized by increased human-to-human transmission was detected outside the endemic regions. Whole genome sequencing (WGS) has been successfully used to keep track of viral evolution during outbreaks or for surveillance of multiple pathogens of public health significance. Current WGS protocols for MPXV are either based on metagenomic sequencing or tiled-PCR amplification. The latter allows multiplexing due to the efficient enrichment of the viral DNA, however, mutations or the presence of different clades can negatively influence genome coverage yield. Here, we present the establishment of a novel isothermal WGS method for MPXV based on Phi29 DNA polymerase-based multiple displacement amplification (MDA) properties making use of only 6 primers. This approach yielded from 88% up to 100% genome coverage using either alkaline denatured extracted DNA or clinical material as starting material, with the highest coverage generated by clinical material. We demonstrate that this novel isothermal WGS protocol is suitable for monitoring viral evolution during MPXV outbreaks and surveillance in any conventional laboratory setting.

Emerging Monkeypox Virus Sublineage C.1 Causing Community Transmission, Vietnam, 2023.

We studied a community cluster of 25 mpox cases in Vietnam caused by emerging monkeypox virus sublineage C.1 and imported into Vietnam through 2 independent events; 1 major cluster carried a novel APOBEC3-like mutation. Three patients died; all had advanced HIV co-infection. Viral evolution and its potential consequences should be closely monitored.

Molecular Aspects of the Monkeypox Virus and their Impact on the Virus's Change in Epidemiology.

OBJECTIVE: Monkeypox is a viral zoonotic disease endemic to West and Central Africa; it has been reported in more countries during the last decade than in the previous 40 years. In 2022 a multinational outbreak occurred. This change in the epidemiology of the virus may represent an evolutionary adaptation. The purpose of this study is to analyze the molecular aspects of Monkeypox virus (MPXV) disease that may explain the latter's change in epidemiology during the 2022 outbreak. METHODS: From July 2022 through December 2022, the period of the outbreak, a narrative review was conducted on the available literature, with a total of 271 articles published in the MEDLINE/PubMed and LILACS databases being examined. The chosen articles were organized using the search and reference manager Mendeley Desktop 1.19.4. Duplicates and articles that did not meet the study's objective were eliminated, resulting in the selection of 49 articles for the present review. DISCUSSION: MPXV resurgence poses challenges due to waning immunity and changing epidemiological patterns. Recent outbreaks show different transmission routes, affecting new demographics. Genomic evolution, vaccination history, and potential new animal reservoirs complicate containment efforts. Continued surveillance and vaccination are crucial for control. CONCLUSIONS: It seems possible that MPXV has (re-)emerged to occupy the ecological niche left by the smallpox virus. Mutations of the apolipoprotein B mRNA editing enzyme, catalytic subunit 3G motif, in MPXV clade IIb since 2017 may explain the epidemiological change that has occurred in recent years. This pattern could be due to sustained transmission in a new host or a new route of infection.

Co-circulation of monkeypox virus subclades Ia and Ib in Kinshasa Province, Democratic Republic of the Congo, July to August 2024.

Between January and August 2024, mpox cases have been reported in nearly all provinces of the Democratic Republic of the Congo (DRC). Monkeypox virus genome sequences were obtained from 11 mpox cases' samples, collected in July-August 2024 in several health zones of Kinshasa. Characterisation of the sequences showed subclades Ia and Ib co-circulating in the Limete health zone, while phylogenetic analyses suggested multiple introductions of the two subclades in Kinshasa. This illustrates the growing complexity of Clade I mpox outbreaks in DRC.

One Health Investigation into Mpox and Pets, United States.

Monkeypox virus (MPXV) is zoonotic and capable of infecting many mammal species. However, whether common companion animals are susceptible to MPXV infection is unclear. During July 2022-March 2023, we collected animal and environmental swab samples within homes of confirmed human mpox case-patients and tested for MPXV and human DNA by PCR. We also used ELISA for orthopoxvirus antibody detection. Overall, 12% (22/191) of animal and 25% (14/56) of environmental swab samples from 4 households, including samples from 4 dogs and 1 cat, were positive for MPXV DNA, but we did not detect viable MPXV or orthopoxvirus antibodies. Among MPXV PCR-positive swab samples, 82% from animals and 93% from environment amplified human DNA with a statistically significant correlation in observed cycle threshold values. Our findings demonstrate likely DNA contamination from the human mpox cases. Despite the high likelihood for exposure, we found no indications that companion animals were infected with MPXV.

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.

As Mpox Cases Surge in Africa, WHO Declares a Global Emergency-Here's What to Know.

This Medical News article discusses the World Health Organization's emergency declaration related to an mpox outbreak in Africa and the emergence of a new virus strain spread by sexual contact.

Multi-omics characterization of the monkeypox virus infection.

Multiple omics analyzes of Vaccinia virus (VACV) infection have defined molecular characteristics of poxvirus biology. However, little is known about the monkeypox (mpox) virus (MPXV) in humans, which has a different disease manifestation despite its high sequence similarity to VACV. Here, we perform an in-depth multi-omics analysis of the transcriptome, proteome, and phosphoproteome signatures of MPXV-infected primary human fibroblasts to gain insights into the virus-host interplay. In addition to expected perturbations of immune-related pathways, we uncover regulation of the HIPPO and TGF-ß pathways. We identify dynamic phosphorylation of both host and viral proteins, which suggests that MAPKs are key regulators of differential phosphorylation in MPXV-infected cells. Among the viral proteins, we find dynamic phosphorylation of H5 that influenced the binding of H5 to dsDNA. Our extensive dataset highlights signaling events and hotspots perturbed by MPXV, extending the current knowledge on poxviruses. We use integrated pathway analysis and drug-target prediction approaches to identify potential drug targets that affect virus growth. Functionally, we exemplify the utility of this approach by identifying inhibitors of MTOR, CHUK/IKBKB, and splicing factor kinases with potent antiviral efficacy against MPXV and VACV.