Mpox, is a zoonotic disease caused by the monkeypox virus and is primarily endemic to Africa. As countries gradually stop smallpox vaccination, resistance to the smallpox virus is declining, increasing the risk of infection with mpox and other viruses. On 14 August 2024, the World Health Organization announced that the spread of mpox constituted a public health emergency of international concern. Mpox's transmission routes and symptoms are complex and pose new challenges to global health. Several vaccines (such as ACAM2000, JYNNEOS, LC16m8, and genetically engineered vaccines) and antiviral drugs (such as tecovirimat, brincidofovir, cidofovir, and varicella immunoglobulin intravenous injection) have been developed and marketed to prevent and control this disease. This review aims to introduce the epidemic situation, epidemiological characteristics, physiological and pathological characteristics, and preventive measures for mpox in detail, to provide a scientific basis for the prevention and control of mpox viruses worldwide.

Methyltransferase VP39 is an important target for the treatment of monkeypox, and inhibition of VP39 can effectively suppresses the transcription and translation of early viral RNA. However, very few inhibitors have been designed against VP39 and other viral MTases. In this work, four inhibitors (SFG, TO507, TO427 and TO1119) were used to investigate the binding mechanism with VP39. Moreover, VP39 has different modes of existence, but we do not understand the interaction mechanism of the complex system formed by the inhibitors with different modes of VP39, so we performed 1000 ns molecular dynamics simulations of the complexes formed by four inhibitors with VP39 in mode 1 and mode 2, and performed energy calculation and conformational analysis. The results of binding free energy showed that in the inhibitors-VP39 (mode 1) systems, TO507 and TO427 had a strong inhibitory effect on VP39, and residues ASP95, ARG97, PHE115 and VAL139 played important roles in the binding process of all four systems. Surprisingly, in the inhibitors-VP39 (mode 2) systems, four inhibitors underwent a large conformational change, with the amino acid moieties of the inhibitors undergoing a nearly 90° folding. And this change reduced the inhibitory effect of the inhibitors on VP39. In addition, the inhibitor TO507 also had a good inhibition effect on nsp14 of SARS-CoV-2 and NS5 of Zika virus. Therefore, this study suggests new ideas for the design and improvement of pan-MTase inhibitors, which are important for the treatment of pandemic infectious diseases, such as monkeypox and SARS-CoV-2.

This review focuses on the temporal relationship between the discontinuation of the global smallpox eradication effort with the rise of mpox in Africa and worldwide. It also discusses the global 2022 clade II mpox epidemic and the current 2024 clade I mpox outbreak. Newer findings on viral evolution and pathogenesis, plus current and future strategies for disease prevention, are reviewed.

The temporal association between the incidence of mpox and the World Health Organization's Global Smallpox Eradication Program (GSEP) is presented. The 2022 global mpox epidemic is discussed. Recent data show that clade IIb monkeypox virus (MPXV)-2022 has novel genetic features supporting a greater propensity for mutations that may be responsible for enhanced human-to-human transmissibility, increased disease severity and accelerated viral evolution. In 2023, another outbreak of mpox began in Africa, this time due to the potentially more virulent MPXV clade Ib strains. This outbreak remains ongoing in Africa, and clade Ib mpox cases have recently been reported elsewhere including the United States and Great Britain. The World Health Organization has deemed mpox to be a global public health emergency. Two smallpox vaccines are approved for mpox prevention in the United States; a third smallpox vaccine and an improved diagnostic test have recently received WHO Emergency Use authorization. Newer mRNA-based vaccines for evolving orthopoxvirus infections are discussed.

Vaccination to prevent smallpox provides immunologic cross-protection against infection with other members of genus Orthopoxvirus , including mpox. Discontinuation of the global smallpox eradication program in the 1980s and the subsequent waning of herd immunity contributed to the 2022 multinational epidemic of human clade IIb mpox infections. A second multinational outbreak with clade Ib MPXV is ongoing. Vaccination against smallpox remains the gold standard for mpox prevention, however newer multiepitope mRNA-based vaccines are in development and hold promise for prevention of mpox and other orthopoxvirus outbreaks.

Monkeypox virus (MPXV) is a DNA virus from the Orthopoxvirus genus, sharing significant genomic similarity with the variola virus that causes smallpox. The cessation of smallpox vaccinations has contributed to recent Mpox outbreaks, with reduced immunity levels, particularly in younger populations born after the vaccine was discontinued. The virus triggers innate and adaptive immune responses, with toll-like receptors (TLRs) playing a key role in recognizing viral components and activating proinflammatory cytokines. However, MPXV evades the immune system by producing proteins that inhibit immune signaling pathways. Natural killer (NK) cells and interferons are crucial for early defense, but MPXV impairs their function. Adaptive immunity involves robust antibody and T-cell responses, similar to smallpox vaccination responses. Various mRNA-based candidate vaccines have demonstrated strong immunogenicity, with preclinical studies confirming their ability to trigger potent B-cell and T-cell responses. However, the genetic changes observed in the current outbreak strains necessitate ongoing surveillance of MPXV mutations and their impact on immunogenic proteins. This review aimed to summarize current insights into antigen recognition and immune responses to MPXV, with a focus on key antigenic proteins relevant to vaccine development.

Monkeypox (Mpox) is a major global human health threat after COVID-19. Its treatment becomes complicated with type-2 diabetes (T2D). It may happen due to the influence of both disease-causing common host key genes (cHKGs). Therefore, it is necessary to explore both disease-causing cHKGs to reveal their shared pathogenetic mechanisms and candidate drugs as their common treatments without adverse side effect. This study aimed to address these issues. At first, 3 transcriptomics datasets for each of Mpox and 6 T2D datasets were analyzed and found 52 common host differentially expressed genes (cHDEGs) that can separate both T2D and Mpox patients from the control samples. Then top-ranked six cHDEGs (HSP90AA1, B2M, IGF1R, ALD1HA1, ASS1, and HADHA) were detected as the T2D-causing cHKGs that are associated with the complexity of Mpox through the protein-protein interaction network analysis. Then common pathogenetic processes between T2D and Mpox were disclosed by cHKG-set enrichment analysis with biological processes, molecular functions, cellular components and Kyoto Encyclopedia of Genes and Genomes pathways, and regulatory network analysis with transcription factors and microRNAs. Finally, cHKG-guided top-ranked three drug molecules (tecovirimat, vindoline, and brincidofovir) were recommended as the repurposable common therapeutic agents for both Mpox and T2D by molecular docking. The absorption, distribution, metabolism, excretion, and toxicity and drug-likeness analysis of these drug molecules indicated their good pharmacokinetics properties. The 100-ns molecular dynamics simulation results (root mean square deviation, root mean square fluctuation, and molecular mechanics generalized born surface area) with the top-ranked three complexes ASS1-tecovirimat, ALDH1A1-vindoline, and B2M-brincidofovir exhibited good pharmacodynamics properties. Therefore, the results provided in this article might be important resources for diagnosis and therapies of Mpox patients who are also suffering from T2D.

The mpox disease, caused by the mpox virus (MPXV), has become a rising public health issue due to its potential to cause outbreaks. Consistently, this investigation aims to evaluate the current advances in the development of novel immunotherapeutic approaches against MPXV, which are crucial for preventing and controlling mpox spread.

This scoping review was performed by analyzing the content of English-language articles published between 2018 and 2024, which reported the development of next-generation vaccines against MPXV and their assessment in animal models. Patents within the scope of this research were also included. Contrarywise, studies based solely on immunoinformatic methods, reviews, book chapters, news, and others were excluded. The literature search was executed in 11 databases, such as Scopus, MEDLINE, and PubMed.

A total of 36 records (32 studies and 4 patents) were included in this review. All 32 articles contain preclinical studies with varied group sizes (4-16) in which the main animal models were BALB/c mice. Less commonly used models included CAST/Ei mice and cynomolgus macaques. Moreover, most vaccines targeted one or more MPXV antigens, such as A29L, A35R, B6R, and M1R, through active immunization (via mRNAs or recombinant antigens) or passive immunization (antibody delivery).

Overall, new generation vaccines might represent prospective candidates to combat the mpox health concern. Nonetheless, several of the analyzed studies possess drawbacks, including animal models with limited similarity to humans, small group sizes, and brief follow-up durations. Consequently, additional research is required to ascertain the long-term protection, efficacy, and safety of these immunotherapeutic approaches.

As the COVID-19 pandemic situation was on an end, a new monkeypox menace has been discovered in several places of the world. The most comforting thing is that the fatality rate of monkeypox is unlike Covid-19. But the recent global outbreaks and the rise in the number of cases has drawn attention of world towards it. The number of cases in multiple countries have already surpassed 25,000, according to the WHO report released on July 25, 2022. The zoonotic disease monkey-pox virus causes a feverish sickness in humans, with characteristic skin rashes and is similar to smallpox in structure, clinical presentation, and response to antiviral medicine. This review offers important insights on the evolution of the monkeypox virus and its different modes of transmission. It also discusses epidemiology, clinical findings, management, challenges, and current strategies for the disease, as well as the implications of the current epidemic on public health. Comprehensive research on the pathophysiology and management of monkeypox is still lacking. In order to solve this problem, we reviewed the pathology and virology of monkeypox infection and provided an overview of the most recent developments in anti-monkeypox medications.

Human monkeypox (Mpox) is a zoonotic disease caused by monkeypox virus (MPXV) present in western Africa and exported sporadically worldwide. MPXV causes illness in individuals and pregnant women which constitute a population at risk with obstetrical and fetal complications including miscarriage, stillbirth and premature delivery. There are accumulated data suggesting a vertical transmission of MPXV from mother to fetus. This review provides an overview of the literature on MPXV infection in pregnant women with a specific focus on vertical transmission.

The persistent monkeypox outbreaks intensify the demand for monkeypox vaccines. Based on the mRNA vaccine platform, we conduct a systematic screening of monkeypox virus (MPXV) surface proteins from two types of viral particles, extracellular enveloped viruses (EVs) and intracellular mature viruses (MVs). This screening unveils 12 important antigens with diverse levels of neutralizing immunogenicity. Further assessment reveals that the combinations of 4, 8, and 12 of these antigens, namely Mix-4, Mix-8, and Mix-12, induce varying degrees of immune protection, with Mix-12 being the most potent. This finding demonstrates the significance of not only the level but also the diversity of the neutralizing antibodies in providing potent immune protection. Additionally, we utilize a T cell-epitope enrichment strategy, analyzing the complete proteome sequence of the MPXV to predict antigenic epitope-rich regions. Integration of these epitope-rich regions into a cellular immune-targeting antigen, named MPX-EPs, showcases that a cellular immune-targeting mRNA vaccine can independently confer immune protection. Furthermore, co-immunization with Mix-12 and MPX-EPs achieves complete protection against MPXV challenge. Overall, these results suggest an effective approach to enhance the immune protection of mRNA vaccines through the specific coordination of humoral and cellular immune responses.

Mpox is a zoonotic disease caused by the monkeypox virus (MPV), primarily found in Central and West African countries. The typical presentation of the disease before the 2022 mpox outbreak includes a febrile prodrome 5-13 days post-exposure, accompanied by lymphadenopathy, malaise, headache, and muscle aches. Unexpectedly, during the 2022 outbreak, several cases of atypical presentations of the disease were reported, such as the absence of prodromal symptoms and the presence of genital skin lesions suggestive of sexual transmission. As per the World Health Organization (WHO), as of March 20, 2024, 94,707 cases of mpox were reported worldwide, resulting in 181 deaths (22 in African endemic regions and 159 in non-endemic countries). The United States Centers for Disease Control and Prevention (CDC) reports a total of 32,063 cases (33.85% of total cases globally), with 58 deaths (32.04% of global deaths) due to mpox. Person-to-person transmission of mpox can occur through respiratory droplets and sustained close contact. However, during the 2022 outbreak of mpox, a high incidence of anal and perianal lesions among MSMs indicated sexual transmission of MPV as a major route of transmission. Since MSMs are disproportionately at risk for HIV transmission. In this review, we discusses the risk factors, transmission patterns, pathogenesis, vaccine, and treatment options for mpox among MSM and people living with HIV (PLWH). Furthermore, we provide a brief perspective on the evolution of the MPV in immunocompromised people like PLWH.

The emergence or reemergence of monkeypox (Mpox) and Ebola virus (EBOV) agents causing zoonotic diseases remains a huge threat to human health. Our study aimed at designing a multi-epitope vaccine (MEV) candidate to target both the Mpox and EBOV agents using immunoinformatics tools. Viral protein sequences were retrieved, and potential nonallergenic, nontoxic, and antigenic epitopes were obtained. Next, cytotoxic and helper T-cell (CTL and HTL, respectively) and B-cell (BCL) epitopes were predicted, and those potential epitopes were fused utilizing proper linkers. The in silico cloning and expression processes were implemented using Escherichia coli K12. The immune responses were prognosticated using the C-ImmSim server. The MEV construct (29.53 kDa) included four BCL, two CTL, and four HTL epitopes and adjuvant. The MEV traits were pertinent in terms of antigenicity, non-allergenicity, nontoxicity, physicochemical characters, and stability. The MEV candidate was also highly expressed in E. coli K12. The strong affinity of MEV-TLR3 was confirmed using molecular docking and molecular dynamics simulation analyses. Immune simulation analyses unraveled durable activation and responses of cellular and humoral arms alongside innate immune responses. The designed MEV candidate demonstrated appropriate traits and was promising in the prediction of immune responses against both Mpox and EBOV agents. Further experimental assessments of the MEV are required to verify its efficacy.

Understanding the pathogenesis mechanism of the Monkeypox virus (MPXV) is essential to guide therapeutic development against the Monkeypox virus. In the current study, we investigated the impact of the only two reported substitutions, S30L, D88N, and S30L-D88N on the G9R of the replication complex in 2022 with E4R using structural modeling, simulation, and free energy calculation methods. From the molecular docking and dissociation constant (KD) results, it was observed that the binding affinity did not increase in the mutants, but the interaction paradigm was altered by these substitutions. Molecular simulation data revealed that these mutations are responsible for destabilization, changes in protein packing, and internal residue fluctuations, which can cause functional variance. Additionally, hydrogen bonding analysis revealed that the estimated number of hydrogen bonds are almost equal among the wild-type G9R and each mutant. The total binding free energy for the wild-type G9R with E4R was -85.00 kcal/mol while for the mutants the TBE was -42.75 kcal/mol, -43.68 kcal/mol, and -48.65 kcal/mol respectively. This shows that there is no direct impact of these two reported mutations on the binding with E4R, or it may affect the whole replication complex or any other mechanism involved in pathogenesis. To explore these variations further, we conducted PCA and FEL analyses. Based on our findings, we speculate that within the context of interaction with E4R, the mutations in the G9R protein might be benign, potentially leading to functional diversity associated with other proteins.Communicated by Ramaswamy H. Sarma.

An underestimated worldwide health concern, Monkeypox (Mpox) is becoming a bigger menace to the world's population. After smallpox was eradicated in 1970, Mpox was found in a rural region of Africa and quickly spread to other African countries. The etiological agent of the Mpox infection, the Mpox virus, is constantly evolving, and its capability for cross-species transmission led to a global outbreak in 2022 which led to several deaths throughout the world. This review aims to showcase the progressive treatment methods and emerging innovations in the diagnostic and prevention strategies for controlling Mpox. The clinical trial data for antiviral drugs were systematically collected and analyzed using statistical tests to determine the most effective antiviral treatment. Emerging viral protein inhibitors that are under investigation for Mpox treatment were also scrutinized in this review. Additionally, modern diagnostic methods, such as the Streamlined CRISPR On Pod Evaluation platform (SCOPE) and graphene quantum rods were reviewed, and the efficacy of mRNA vaccines with traditional smallpox vaccines used for Mpox were compared. The statistical analysis revealed that tecovirimat (TCV) is the most effective antiviral drug among the other evaluated drugs, showing superior efficacy in clinical trials. Similarly, mRNA vaccines offer greater effectiveness compared to conventional smallpox vaccines. Furthermore, emerging nanomedicine and herbal drug candidates were highlighted as potential future treatments for Mpox. The findings underscore the effectiveness of TCV in treating Mpox and highlight significant advancements in preventive treatments. The review also points to innovative approaches in vaccine technology and potential future therapies, including nanomedicine and herbal remedies, which may enhance Mpox management.

The 2022 Mpox virus (MPXV) outbreak revitalized questions about immunity against MPXV and vaccinia-based vaccines (VAC-V), but studies are limited. We analyzed immunity against MPXV in individuals infected with MPXV or vaccinated with the licensed modified vaccinia Ankara (MVA) Bavarian Nordic or an experimental MVA-HIVB vaccine. The frequency of neutralizing antibody responders was higher among MPXV-infected individuals than MVA vaccinees. Both MVA vaccines induced similar and strong humoral responses. Similarly, we show a higher frequency and magnitude (5-fold) of T cell responses, mainly mediated by CD8+ T cells, against a peptide pool containing selected sequences from MPXV, variola, and VAC-V in MPXV-infected individuals than MVA vaccinees. We describe a hierarchy of cross-reactive T cell responses against 5 peptide pools that are highly homologous between VAC-V and MPXV 2022, with the highest frequency of responders against MVA-121L and MVA-018L proteins. Both vaccines stimulated a notable frequency of polyfunctional CD4+ and CD8+ T cell responses, with a subset of CD4+ T cells showing a mixed cytokine profile. Finally, we found that smallpox vaccination in childhood positively affected humoral but not T cell vaccine responses, whereas these responses were not affected in people living with HIV. These findings contribute to deciphering and monitoring the profile of immunity to MPXV and MVA. In the context of a potential threat of the reemergence of smallpox following bioterrorism, the diversification and availability of potent vaccines is crucial. The comparable immunogenicity of both MVA vaccines emphasizes the potential utility of MVA-HIVB as a valuable new tool for controlling MPXV outbreaks.

The vaccinia virus (VV) is extensively utilized as a vaccine vector in the treatment of various infectious diseases, cardiovascular diseases, immunodeficiencies, and cancers. The vaccinia virus Tiantan strain (VVTT) has been instrumental as an irreplaceable vaccine strain in the eradication of smallpox in China; however, it still presents significant adverse toxic effects. After the WHO recommended that routine smallpox vaccination be discontinued, the Chinese government stopped the national smallpox vaccination program in 1981. The outbreak of monkeypox in 2022 has focused people's attention on the Orthopoxvirus. However, there are limited reports on the safety and toxic side effects of VVTT. In this study, we employed a combination of transcriptomic analysis and machine learning-based feature selection to identify key genes implicated in the VVTT infection process. We utilized four machine learning algorithms, including random forest (RF), minimum redundancy maximum relevance (MRMR), eXtreme Gradient Boosting (XGB), and least absolute shrinkage and selection operator cross-validation (LASSOCV), for feature selection. Among these, XGB was found to be the most effective and was used for further screening, resulting in an optimal model with an ROC curve of 0.98. Our analysis revealed the involvement of pathways such as spinocerebellar ataxia and the p53 signaling pathway. Additionally, we identified three critical targets during VVTT infection-ARC, JUNB, and EGR2-and further validated these targets using qPCR. Our research elucidates the mechanism by which VVTT infects cells, enhancing our understanding of the smallpox vaccine. This knowledge not only facilitates the development of new and more effective vaccines but also contributes to a deeper comprehension of viral pathogenesis. By advancing our understanding of the molecular mechanisms underlying VVTT infection, this study lays the foundation for the further development of VVTT. Such insights are crucial for strengthening global health security and ensuring a resilient response to future pandemics.

Given the surge in mpox outbreaks in 2022 and the advancements in domestic and international vaccine research, the effectiveness of smallpox vaccines in providing cross-protection against mpox remains crucial. Having learned from the COVID-19 pandemic, it is significant to continue evaluating existing vaccines to ensure their safety and efficacy. Developing new vaccines for widespread use against mpox and its emerging strains also serves as a preventive strategy in the ongoing battle against this dynamic infection. Here's an opportunity to control human-to-human transmission, give short deadlines, and avoid vaccine disparity. Public health systems must take decisive action to prevent the global spread of mpox, particularly among vulnerable groups. This action should include strengthening global surveillance, improving vaccine access, and ensuring equitable distribution, particularly in resource-poor settings, to prevent future outbreaks. This review aims to assess recent advancements and barriers in mpox vaccine development, emphasizing cross-protection and equitable vaccine distribution in resource-poor settings.

Dermatological vaccines have emerged as critical tools in preventing and managing a wide spectrum of skin conditions ranging from infectious diseases to malignancies. By synthesizing evidence from existing literature, this review aims to comprehensively evaluate the efficacy, safety, and immunogenicity of vaccines used in dermatology, including both approved vaccines and those currently being researched. Vaccines discussed in this paper include those targeting dermatoses and malignancies (e.g., acne vulgaris, atopic dermatitis, and melanoma); infectious diseases (e.g., human papillomavirus (HPV); varicella zoster virus (VZV); herpes zoster (HZ); warts; smallpox; mpox (monkeypox); hand, foot, and mouth disease (HFMD); candidiasis and Group B Streptococcus (GBS); and neglected tropical diseases (e.g., Buruli ulcer, leprosy, and leishmaniasis). Through this review, we aim to provide a detailed understanding of the role of vaccines in dermatology, identify knowledge gaps, and propose areas for future research.

Monkeypox (mpox) is a viral infection closely related to smallpox, manifesting as a milder febrile rash in affected individuals. Over the past two decades, the incidence of mpox has surged, possibly linked to a declining immunity against the smallpox vaccine worldwide. Recent outbreaks of mpox in multiple countries have sparked concerns regarding altered transmission patterns and the potential for a global menace. In this article, we present a multidimensional review encompassing the latest scientific discoveries, illuminating the intricate structure of the human mpox virus. Key findings include advancements in understanding the virus's molecular mechanisms, which highlight its genetic adaptability and potential for zoonotic spillover. Diagnostic innovations, such as improved molecular assays, have enhanced detection accuracy, while novel therapeutic strategies, including antiviral drugs and vaccines, show promise in mitigating outbreaks. Our conclusions emphasize the importance of robust surveillance systems, vaccination programs, and rapid response strategies to curb mpox's spread. Future recommendations include strengthening global collaboration for zoonotic disease surveillance, advancing the research on host-pathogen interactions, and developing next-generation therapeutics to address this emerging public health threat effectively.

Monkeypox, a zoonotic virus in the Orthopoxvirus genus, has drawn global attention for its impact on public health. In the current Mpox outbreak, a novel clade, Ib, has emerged as a significant and potentially fatal threat. This review examines the dynamics of MPXV transmission, person-to-person spread, and infection mechanisms, highlighting key risk factors. We explore the clinical features of Mpox, focusing on symptomology, illness duration, and the distinguishing characteristics of clade Ib compared to other clades. A critical analysis addresses diagnostic techniques and emphasizes the need for robust surveillance, particularly for clade Ib detection. We review recent prevention and treatment strategies, including antiviral drugs and vaccines, with a focus on clade Ib containment. The conclusion underscores the urgency of global collaboration to prevent and prepare for emerging threats like clade Ib and identifies crucial research paths and knowledge gaps. This review offers a comprehensive overview of clade Ib, covering its emergence, genetic traits, epidemiological impact, transmission patterns, clinical features, the role of Artificial Intelligence (AI) in outbreak management, detection challenges, and implications for public health response.

Monkeypox (Mpox) is an infectious disease caused by the Mpox virus belonging to the Orthopoxvirus genus in the Poxviridae family and has been declared by the WHO as a global health emergency owing to its rapid spread during 2022 and 2023. All patients diagnosed with Mpox who were confirmed by PCR between July 2022 and April 2023 were included in this study. In total, 405 patients in whom clade 2 was identified were included. Notably, 99% of included patients were men, with 82% of them aged 20-39 years. Furthermore, 71% were men who had sex with men, and 34% were HIV carriers. Regarding the morphology of the lesions, approximately 63% presented with papulonecrotic rash, which sometimes alternated with pustules depending on the stage they were in. All patients presented with systemic symptoms. Five patients required hospital admission, one of whom died, and presented with HIV and severe immunosuppression. Clinical findings suggest that contact during sexual intercourse is the most likely transmission mechanism and genital involvement is the most frequent clinical form. HIV was the primary comorbidity. Genital lesions were common, especially in vulnerable populations such as those who engage in high-risk sexual behaviors.

Monkeypox is a zoonotic disease caused by the orthopox virus, a double-stranded DNA virus that belongs the Poxviridae virus family. It is known to infect both animals (especially monkeys and rodents) and humans and causes a rash similar to smallpox. Humans can become infected with monkeypox virus (MPXV) when they get in close contact with infected animals (zoonotic transmission) or other infected people (human-human transmission) through their body fluids such as mucus, saliva, or even skin sores. Frequently observed symptoms of this disease include fever, headaches, muscle aches, and a rash that initially looks like a tiny bump before becoming a lump that is filled with fluid. Monkeypox symptoms also include an incubation period of 5-21 days, divided into prodromal and eruption phases. Several contributing factors, such as smallpox vaccine discontinuation, widespread intake of infected animal products as a source of protein, and high population density, amongst others, have been linked to an increase in the frequency of monkeypox outbreaks. The best course of action for diagnosing individuals who may be suffering from active monkeypox is to collect a sample of skin from the lesion and perform PCR molecular testing. Monkeypox does not presently have a specific therapy; however, supportive care can assist in managing symptoms, such as medication to lower body temperature and pain. Three major orthopoxvirus vaccines have been approved to serve as a preventive measure against monkeypox: LC16, JYNNEOS, and ACAM2000. The discovery that the monkeypox outbreak is communicable both among humans and within a population has sparked new public health worries on the possibility of the outbreak of another viral pandemic. Research and studies are still being conducted to gain a deeper understanding of this zoonotic viral disease. This review is therefore focused on deciphering monkeypox, its etiology, pathogenesis, transmission, risk factors, and control.

Monkeypox (Mpox) has once again been designated a Public Health Emergency of International Concern (PHEIC) as of August, 2024. The severity of the disease is underscored by its significant mortality rate, and unfortunately, there are no targeted therapeutics currently available for this viral infection. Management relies on preventive measures and the use of existing smallpox vaccines due to their genetic similarity to the Mpox virus. Diagnosing a disease is a critical aspect of managing any health condition, and for a highly contagious viral infection like Mpox, it is essential to employ a specific and sensitive diagnostic approach. The lack of adequate diagnostic facilities in laboratories poses a significant challenge, hindering accurate diagnoses and the identification of underlying etiologies, particularly in low-resource settings. Current serology-based diagnostic tests lack specificity for the Mpox virus, leading to cross-reactivity with other orthopoxviruses. With the emergence of new viral variants, molecular and genomic diagnostic methods are far more reliable for accurately confirming Mpox infections. This review focuses on current diagnostic methods approved worldwide and the future challenges that need to be addressed to effectively control and mitigate the spread of Mpox.

The monkeypox outbreak has grown beyond the regions in which it was considered endemic. It has spread from central and west Africa to non-endemic regions like Europe, America, and other parts of the world. It has recently been classified as a public health emergency of international concern. This study evaluated the challenges faced globally and equitable access to monkeypox vaccines. Global competition has been observed in the race to obtain vaccines, with low- and middle-income countries being disadvantaged. Great inequity exists in the distribution of vaccines globally through advance purchase agreements, vaccine stockpiling, vaccine nationalism, the inequitable distribution of existing resources, and insufficient surveillance and reporting mechanisms. To address some of these challenges, there is a need for strengthening the global vaccine manufacturing capacity, targeting countries with elevated risk profiles and limited resources, strengthening surveillance systems, and addressing vaccine hesitancy.

In the recent mpox outbreak, people with human immunodeficiency virus (PWH) were at high risk both for contracting infection and for a more severe disease course. We studied cellular and humoral immune responses elicited by mpox infection (n = 5; n = 3 PWH) or smallpox vaccination (n = 17; all PWH) in a cohort of men who have sex with men. All PWH were successfully treated, with stable CD4 counts and undetectable HIV viral loads. Eleven of 17 vaccinated individuals had received childhood smallpox vaccination. In this group of individuals, both 2-dose modified vaccinia Ankara (MVA) vaccination and natural infection evoked mpox-specific immune responses mediated by B cells as well as CD4 and CD8 T cells. This study improves our understanding of smallpox vaccination-mediated cross-reactivity to other orthopox viruses, and long-lasting durability of childhood smallpox vaccination-mediated immune responses, including in PWH.

Background Monkeypox (Mpox) is a virulent disease caused by orthopoxvirus. Mpox is emerging as a major global health threat. Currently, more than 100 countries are facing outbreaks. Pakistan, too, is witnessing the spread of this virus, with 11 confirmed cases and one death since its first detection in April 2023. Mpox infection can be diagnosed using polymerase chain reaction (PCR) and treated with antiviral agents. The smallpox vaccine is also proven to be effective against Mpox. Methodology This cross-sectional survey aimed to evaluate the knowledge, attitude, and behaviors (KAB) of the Pakistani population toward the Mpox pandemic and determine the factors affecting it. Data were collected through Google Forms using a validated questionnaire to assess the population's KAB. In total, 1,511 individuals were included in the final analysis. Results Study participants had good knowledge of the disease, poor attitude toward Mpox risk and severity, and poor behavior with low adherence to recommended protocols. Overall, 58% (n = 888) of the participants were male, and most of the respondents were aged between 18 and 30 years (n = 743, 49.2%). Most participants were married (n = 983, 65.1%), from urban areas (n = 837, 55.4%), and living in shared households (n = 876, 58%). Age showed a significant relationship with knowledge level and behavior, but not with attitude. The 18-30-year age group demonstrated higher knowledge levels (p = 0.007), regardless of gender. Shared households were significantly associated with a higher incidence of good knowledge (p < 0.05) compared to independent households (p = 0.038). Additionally, higher income was linked to better attitudes and behaviors. KAB outcomes also varied significantly based on marital status, individual education level, and parents' education levels. Conclusions Population dynamics such as cultural norms, religious beliefs, misperceptions about the disease associated with sexual behavior, health literacy, education level, rural and urban division of the population, gender role, migrant and refugee population, poverty, cost-seeking healthcare, and distrust in the government and healthcare system should be considered when constructing a public health policy because the behavior of the population is important for the implementation of preventive measures.

Mpox continues to spread in China, and stakeholders' experiences may help inform prevention and control strategies.

Qualitative study.

A qualitative study across 14 Chinese cities recruited stakeholders from Centers for Disease Control and Prevention (CDCs), community-based organizations (CBOs), and hospitals involved in curbing mpox. Semi-structured interviews were conducted by telephone and analyzed using Colaizzi's phenomenological method.

15 CBOs workers, 14 CDCs staff, and 13 healthcare workers were recruited. Three theme categories were identified: "Efforts to curb mpox epidemic", including CDCs' epidemic management and health education, hospitals' diagnosis, treatment, and care, CBOs' counseling, publicity, and referrals. "Challenges to curb mpox epidemic", including negative impacts of hospital-based quarantine, lack of specific antiviral drugs, gay identity disclosure concerns, psychological problems, contact tracing difficulties, and inadequate communication and collaboration. "Recommendations for curbing mpox epidemic", including prioritizing supervised home-based quarantine, incorporating HIV-related indicators into hospital quarantine criteria, reducing the cost of hospital quarantine, accelerating the development of vaccines and drugs, enhancing patient privacy protection, psychological training for stakeholders, establishing a task force that comprises personnel who are experienced in contact tracing and strengthening communication and collaboration.

Effective control of mpox spread requires strengthening collaboration with CBOs and community healthcare centers (CHCs) and working out a flexible and contextualized mechanism. It also needs to reinforce patient privacy protection and integrate stigma reduction into strategies. Additionally, it is important to include HIV-related indicators in the quarantine evaluation and provide psychological training for stakeholders to help them manage their mental health and improve counseling skills.

Background/Objectives: Mpox (monkeypox) is a zoonosis with origins in a currently unknown African reservoir. The first epidemiological accounts of mpox date back to the early 1980s, yet mpox only emerged as a pandemic threat in 2022-2023, more than 40 years later. This scenario is very different from those of other emerging diseases such as HIV and SARS, which immediately spread globally, in fully susceptible populations, starting from patients zero. Methods: We use mathematical modeling to illustrate the dynamics of mpox herd immunity in small communities in touch with the mpox natural reservoir. In particular, we employ an SEIR stochastic model. Results: The peculiar emergence of mpox can be explained by its relationship with smallpox, which was eradicated through universal mass vaccination in 1980. Mpox first emerged in small rural communities in touch with mpox's animal reservoir and then spread globally. The relative isolation of these communities and their herd-immunity dynamics against mpox worked to delay the introduction of mpox in large urban centers. Conclusions: Mathematical modeling suggests that the search for the mpox animal reservoir would be most fruitful in communities with high mpox seroprevalence and small outbreaks. These are communities is tight contact with the mpox natural reservoir. We propose vaccinating individuals in communities in these communities to severely reduce the importation of cases elsewhere.

Multinational epidemics of emerging infectious diseases are increasingly common, due to anthropogenic pressure on ecosystems and the growing connectivity of human populations. Early and efficient vaccination can contain outbreaks and prevent mass mortality, but optimal vaccine stockpiling strategies are dependent on pathogen characteristics, reservoir ecology, and epidemic dynamics. Here, we model major regional outbreaks of Nipah virus and Middle East respiratory syndrome, and use these to develop a generalized framework for estimating vaccine stockpile needs based on spillover geography, spatially-heterogeneous healthcare capacity and spatially-distributed human mobility networks. Because outbreak sizes were highly skewed, we found that most outbreaks were readily contained (median stockpile estimate for MERS-CoV: 2,089 doses; Nipah: 1,882 doses), but the maximum estimated stockpile need in a highly unlikely large outbreak scenario was 2-3 orders of magnitude higher (MERS-CoV: ∼87,000 doses; Nipah ∼ 1.1 million doses). Sensitivity analysis revealed that stockpile needs were more dependent on basic epidemiological parameters (i.e., death and recovery rate) and healthcare availability than any uncertainty related to vaccine efficacy or deployment strategy. Our results highlight the value of descriptive epidemiology for real-world modeling applications, and suggest that stockpile allocation should consider ecological, epidemiological, and social dimensions of risk.

The resurgence of monkeypox causes considerable healthcare risks needing efficient immunization programs. This work investigates the monkeypox disease dynamics in the UK, focusing on the impact of vaccination under real data. The key difficulty is to correctly predict the spread of the disease and evaluate the success of immunization efforts. We construct a mathematical model for monkeypox infection and extend it to the fractional case considering the Caputo derivative. The analysis ensures the positivity, boundedness, and uniqueness of the solution for the non-integer system. We conduct a local asymptotical stability analysis (LAS) at the disease-free equilibrium (DFE) D0, showing the result for R0<1. Additionally, we demonstrate the existence of multiple endemic equilibria and provide conditions for backward bifurcation, which are illustrated graphically. Using real case data from the UK, we estimate model parameters via the nonlinear least square method. Our results show that, without vaccination, R2≈0.8, whereas vaccination reduces it to R2v=0.48. We perform sensitivity analysis to identify key parameters influencing disease elimination, presenting the outcomes through graphs. To solve numerically the fractional model, we outline a numerical scheme and provide detailed results under various parameter assumptions. Our findings suggest that high vaccine efficacy, a low waning rate of the vaccines, and increased vaccination of the infected people can significantly reduce the future cases of monkeypox in the UK. The present study offers a comprehensive framework for monkeypox dynamics and informs public health strategies for effective disease control and prevention.

Monkeypox (Mpox), an uncommon zoonotic Orthopoxvirus, is commonly manifested by blisters on the skin and has a mortality rate of approximately 0-10%. Approximately two decades after the cessation of global smallpox vaccination, the number of confirmed cases of Mpox has been growing, making it the most common Orthopoxvirus infection. Therefore, in this narrative review, we aimed to shed light on recent advancements in the pathophysiology, transmission routes, epidemiology, manifestations, diagnosis, prevention, and treatment of Mpox, as well as the application of artificial intelligence (AI) methods for predicting this disease. The clinical manifestations of Mpox, including the onset of symptoms and dermatologic characteristics, are similar to those of the infamous smallpox, but Mpox is clinically milder. Notably, a key difference between smallpox and Mpox is the high prevalence of lymphadenopathy. Human-to-human, animal-to-human, and animal-to-animal transmission are the three main pathways of Mpox spread that must be considered for effective prevention, particularly during outbreaks. PCR testing, as the preferred method for diagnosing Mpox infection, can enhance early detection of new cases and thereby improve infection control measures. JYNNEOS and ACAM2000 are among the vaccines most commonly recommended for the prevention of Mpox. Brincidofovir, Cidofovir, and Tecovirimat are the primary treatments for Mpox cases. Similar to other viral infections, the best approach to managing Mpox is prevention. This can, in part, be achieved through measures such as reducing contact with individuals displaying symptoms, maintaining personal safety, and adhering to practices commonly used to prevent sexually transmitted infections.

The recent increase in human mpox (monkeypox) cases emphasizes the importance of early detection, prompt response and preventive management to control the spread of the disease. Healthcare workers (HCWs) play a crucial role in this process. This study aimed to determine the global knowledge and attitudes towards mpox among HCWs.

This study searched multiple databases, including Google Scholar, Scopus, PubMed/MEDLINE, Science Direct, Web of Science, Embase, Springer and ProQuest, to locate various publications. The search was limited to English-language articles published between May 2022 (when the increase in mpox incidence was reported) and August 2023. The Joanna Briggs Institute (JBI) quality checklist was utilized to evaluate the quality of the included studies. Data were obtained using a Microsoft Excel spreadsheet and subsequently scrutinized through STATA software, version 14. The heterogeneity of the studies was assessed using the inverse variance and Cochran Q statistics based on the I2 test statistics. The Dersimonian and Liard random effects models were used where heterogeneity existed. Subgroup analysis and univariate and multivariable metaregression techniques were used to examine the causes of heterogeneity.

A total of 22 studies, including 22 studies for knowledge (27 731 HCWs) and 6 studies for attitudes (14 388 HCWs), were included in the meta-analysis. The pooled estimates for good knowledge and positive attitudes among HCWs were 26.0% (95% confidence interval [CI] 17.8 to 34.2) and 34.6% (95% CI 19.0 to 50.2), respectively. Moreover, the knowledge was 34.8% (95% CI 24.1 to 45.6) among HCWs with <5 y of work experience and 41.6% (95% CI 33.1 to 50) among individuals possessing >5 y of professional background.

Good knowledge of HCWs is at a low level. It is suggested that training sessions should be tailored towards younger HCWs with less healthcare experience. Additionally, it is essential to identify strategies on how to improve the knowledge and attitudes for better practice about the disease in HCWs worldwide.

Vaccine hesitancy is a significant barrier to achieving high vaccination rates, particularly among men who have sex with men (MSM), a group at increased risk for Mpox. This study aimed to develop and validate a Mpox vaccine hesitancy scale specifically tailored for Chinese MSM, grounded in the protection motivation theory (PMT).

An online survey through snowball sampling was conducted from October 2023 to March 2024, collecting 2403 valid responses across six representative regions in China. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to evaluate the scale's construct validity, while reliability was assessed using Cronbach's α coefficient. The predictive validity of the scale was analyzed using Receiver Operating Characteristic (ROC) analysis.

EFA ultimately retained 22 items in the Mpox vaccination scale and identified four distinct dimensions: Maladaptive Rewards (seven items), Self-efficacy (seven items), Response Efficacy (four items), and Response Costs (four items). These dimensions were confirmed by CFA, which demonstrated satisfactory model fit indices (χ²/df = 4.382, RMSEA = 0.053, SRMR = 0.048, GFI = 0.935, CFI = 0.967, NFI = 0.958, TLI = 0.963, and IFI =0.967). All indices were within acceptable ranges. The scale exhibited good internal consistency, with a Cronbach's alpha of 0.906, and strong content validity, with an S-CVI/Ave of 0.952. The scale's predictive accuracy was evaluated using Receiver Operating Characteristic (ROC) analysis. When used to evaluate the scale's predictive accuracy, it yielded an area under the curve (AUC) of 0.854 after adjustments, indicating good predictive ability between high and low hesitancy.

This scale provides a reliable and valid tool for assessing Mpox vaccine hesitancy among MSM and can be used to gauge Mpox vaccination intention within this group.

Monkeypox virus (MPXV) is another zoonotic virus spilled over to the man and resulted in pandemic. World Health Organization declared it as a 'Public Health Emergency of International Concern (PHEIC) on July 22, 2022. Mpox affected over 95226 individuals among them claimed the lives of 185. Despite the fact that Mpox is generally mild and self-limited, immunocompromised people with low CD4 counts may experience severe disease course. Management of Mpox patients has three pillars. First symptomatic approach includes pain management, prophylaxis for secondary infections and when needed effective treatment of superinfections. Second, vaccines developed against smallpox can be used in preexposure or postexposure prophylaxis strategies against Mpox. Third, current antiviral options include tecovirimat, cidofovir and birincidofovir all of which have been recommended relying on experience from animal studies, clinical case reports or case series. Results of well-planned randomized control trials are not available. Occupational exposure to MPXV is especially a manageable risk for health care workers. Prevention of Mpox also requires risk communication with vulnerable population and their involvement in mitigation efforts.

The increase in mpox incidence underscores the crucial need to understand and effectively address prevention, early detection, and agile response to this disease. Therefore, the present study aims to determine the knowledge and attitude towards mpox.

A systematic review and comprehensive literature meta-analysis were conducted using prominent databases such as PubMed, Scopus, Web of Science, Embase, and ScienceDirect, with an updated search until June 25, 2023. The quality of the included observational studies was assessed using the Joanna Briggs Institute's Statistical Meta-Analysis Review Instrument. The collected data were recorded in a Microsoft Excel spreadsheet, and analyses were conducted using R software version 4.2.3. Additionally, Cochran's Q statistics were applied to assess the heterogeneity of the included studies.

A total of 299 articles were retrieved from 5 databases. This study included 27 cross-sectional articles with a total sample of 22,327 participants, of which 57.13% were women. The studies were conducted in 15 countries through an online survey. All studies had a moderate level of quality. The combined prevalence of a good level of knowledge about mpox was 33% (95% CI: 22%-45%; 22,327 participants; 27 studies; I2 = 100%), and the combined prevalence of a positive attitude towards mpox was 40% (95% CI: 19%-62%; 2,979 participants; 6 studies; I2 = 99%). Additionally, as a secondary outcome, the combined prevalence of the intention to vaccinate against mpox was 58% (95% CI: 37%-78%; 2,932 participants; 7 studies; I2 = 99%).

Good knowledge and a positive attitude towards mpox were found to be low. The findings of this study highlight the need to identify gaps and focus on implementing educational programs on mpox.

Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI), Prospective International Registry of Systematic Reviews (PROSPERO), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

The aim was to estimate the effect of reported history of smallpox vaccination prior to 1980 on clinical expression of mpox.

We included all confirmed mpox cases identified by the national mpox surveillance system in France between May and July 2022. Cases tested positive for monkeypox virus or orthopoxviruses by PCR. Cases were interviewed by phone using a questionnaire documenting demographics, symptoms and exposures. To estimate the effect of smallpox vaccination on the presence of marked mpox symptoms (association of fever, lymphadenopathy and extensive mucocutaneous lesions), we estimated prevalence ratios (PRs) and 95% CIs using Poisson regression models with robust standard errors.

There were 1888 confirmed mpox cases with date of symptom onset between 7 May and 31 July 2022. Overall, 7% (93/1394) presented marked mpox symptoms. Among patients who provided information about their vaccination status, 14% (207/1469) reported smallpox vaccination prior to 1980. The proportion of cases with marked symptoms was 2% (3/170) among those reporting smallpox vaccination prior to 1980 and 8% (76/974) among those who reported no vaccination. The proportion of marked symptoms was four times lower among cases reporting previous smallpox vaccination than in cases reporting no vaccination (PR, 0.24; 95% CI: 0.08-0.76). There was no evidence of an effect of smallpox vaccination on development of complications (PR, 0.65; 95% CI: 0.35-1.22) or hospitalization due to mpox (PR, 0.64; 95% CI: 0.23-1.80).

Our results suggest that smallpox vaccination during childhood attenuated the clinical expression of monkeypox virus infection, but there was no evidence of an effect on complications or hospitalization.

The 2022 global mpox outbreak disproportionately impacted people living with HIV. This review explores recent evidence on mpox in this group, focusing on clinical presentation, complications, treatment modalities and vaccine strategies.

Recent studies have suggested that people with HIV diagnosed with mpox have a greater risk of proctitis and hospitalization compared with people without HIV. In addition, those with advanced immunosuppression face an elevated risk of severe mpox infection, which can lead to mortality. Comprehensive and prompt supportive care using antiretrovirals and mpox antivirals is crucial in this group. Although results from randomized clinical trials are still forthcoming, recent studies suggest that early initiation of tecovirimat can prevent disease progression in people with HIV. The non-replicative attenuated smallpox vaccine is well tolerated and effective in preventing monkeypox virus infections in people with HIV. Further studies are needed regarding long-term vaccine effectiveness for this population.

Evaluating the risk of severe mpox in people living with HIV requires assessing the level of immune suppression and viral control. Universal access to vaccination is imperative to prevent the resurgence of future outbreaks.

We assessed early antibody responses after two doses of JYNNEOS (IMVANEX) mpox vaccine in the District of Columbia (D.C.) in persons at high risk for mpox without characteristic lesions or rash. Participants with PCR mpox negative specimens (oral swab, blood, and/or rectal swab) on the day of receipt of the first vaccine dose and who provided a baseline (day 0) serum sample and at least one serum sample at ∼28, ∼42-56 days, or 180 days post vaccination were included in this analysis. Orthopoxvirus (OPXV)-specific IgG and IgM ELISAs and neutralizing antibody titers were performed, and longitudinal serologic responses were examined. Based on participants' IgG and IgM antibody levels at baseline, they were categorized as naïve or non-naïve. Linear mixed effects regression models were conducted to determine if IgG antibody response over time varied by age, sex, HIV status, and route of administration for both naïve and non-naïve participants. Among both naïve and non-naïve participants IgG seropositivity rates increased until day 42-56, with 89.4 % of naïve and 92.1 % of non-naïve participants having detectable IgG antibodies. The proportion of naive participants with detectable IgG antibodies declined by day 180 (67.7 %) but remained high among non-naïve participants (94.4 %). Neutralizing antibody titers displayed a similar pattern, increasing initially post vaccination but declining by day 180 among naïve participants. There were no significant serologic response differences by age, sex, or HIV status. Serologic response did vary by route of vaccine administration, with those receiving a combination of intradermal and subcutaneous doses displaying significantly higher IgG values than those receiving both doses intradermally. These analyses provide initial insights into the immunogenicity of a two-dose JYNNEOS PEP regimen in individuals at high risk of mpox exposure in the United States.