Expanded Access Programme for the use of tecovirimat for the treatment of monkeypox infection: A study protocol for an Expanded Access Programme.

BACKGROUND: Monkeypox is a viral zoonotic disease commonly reported in humans in parts of Central and West Africa. This protocol is for an Expanded Access Programme (EAP) to be implemented in the Central African Republic, where Clade I monkeypox virus diseases is primarily responsible for most monkeypox infections. The objective of the programme is to provide patients with confirmed monkeypox with access to tecovirimat, a novel antiviral targeting orthopoxviruses, and collect data on clinical and virological outcomes of patients to inform future research. METHODS: The study will be conducted at participating hospitals in the Central African Republic. All patients who provide informed consent to enrol in the programme will receive tecovirimat. Patients will remain in hospital for the duration of treatment. Data on clinical signs and symptoms will be collected every day while the patient is hospitalised. Blood, throat and lesion samples will be collected at baseline and then on days 4, 8, 14 and 28. Patient outcomes will be assessed on Day 14 -end of treatment-and at Day 28. Adverse event and serious adverse event data will be collected from the point of consent until Day 28. DISCUSSION: This EAP is the first protocolised treatment programme in Clade I MPXV. The data generated under this protocol aims to describe the use of tecovirimat for Clade I disease in a monkeypox endemic region of Central Africa. It is hoped that this data can inform the definition of outcome measures used in future research and contribute to the academic literature around the use of tecovirimat for the treatment of monkeypox. The EAP also aims to bolster research capacity in the region in order for robust randomised controlled trials to take place for monkeypox and other diseases. TRIAL REGISTRATION: {2a & 2b}: ISRCTN43307947.

Cross-Country Discrepancies in Monkeypox Vaccine Hesitancy Among Postgraduate and Undergraduate Medical Students.

BACKGROUND: Medical students hold significant importance, as they represent the future of healthcare provision. This study aimed to explore psychological antecedents towards the monkeypox (mpox) vaccines among postgraduate and undergraduate medical students across countries. METHODS: A cross-sectional survey was conducted among medical students aged 18 years old and above in 7 countries; Egypt, Romania, Malaysia, and Yemen, Iraq, India, and Nigeria. We used social media platforms between September 27 and November 4, 2022. An anonymous online survey using the 5C scale was conducted using snowball and convenience Sampling methods to assess the 5 psychological antecedents of vaccination (i.e., confidence, constraints, complacency, and calculation, as well as collective responsibility). RESULTS: A total of 2780 participants were recruited. Participants' median age was 22 years and 52.1% of them were males. The 5C psychological antecedents of vaccination were as follows: 55% were confident about vaccination, 10% were complacent, 12% experienced constraints, and 41% calculated the risk and benefit. Lastly, 32% were willing to be vaccinated for the prevention of infection transmission to others. The Country was a significant predictor of confidence, complacency, having constraints, and calculation domains (P < 0.001). Having any idea about the mpox vaccine was linked to 1.6 times higher odds of being more confident [OR = 1.58 (95% CI, 1.26-1.98), P < 0.001] Additionally, living in a rural area significantly increased complacency [OR = 1.42 (95% CI, 1.05-1.95), P = 0.024] as well as having anyone die from mpox [OR = 3.3 (95% CI, 1.64-6.68), P < 0.001]. Education level was associated with increased calculation [OR = 2.74 (95% CI, 1.62-4.64), P < 0.001]. Moreover, being single and having no chronic diseases significantly increased the calculation domain [OR = 1.40 (95% CI, 1.06-1.98), P = 0.02] and [OR = 1.54 (95% CI, 1.10-2.16), P = 0.012] respectively. Predictors of collective responsibility were age 31-45 years [OR = 2.89 (95% CI, 1.29-6.48), P = 0.01], being single [OR = 2.76 (95% CI, 1.94 -3.92), P < 0.001], being a graduate [OR = 1.59 (95% CI (1.32-1.92), P < 0.001], having no chronic disease [OR = 2.14 (95% CI, 1.56-2.93), P < 0.001], and not knowing anyone who died from mpox [OR = 2.54 (95% CI, 1.39-4.64), P < 0.001), as well as living in a middle-income country [OR = 0.623, (95% CI, 0.51-0.73), P < 0.001]. CONCLUSIONS: This study underscores the multifaceted nature of psychological antecedents of vaccination, emphasizing the impact of socio-demographic factors, geographic location, and awareness, as well as previous experiences on individual attitudes and collective responsibility towards vaccination.

Knowledge, concerns, and vaccine acceptance related to Mpox (Monkeypox) among university students in North and Northeast China: An online cross-sectional study.

The growing number of Mpox cases in China has posed a challenge to public health. The prevalence of men who have sex with men behaviors among students has been consistently increasing each year in China, accompanied by a high frequency of unprotected anal sex. As crowded places, schools are highly likely to cause an Mpox outbreak among students through long-term close contact. Understanding university students' perceptions about Mpox and willingness to vaccinate play a vital role in implementing preventive measures in schools. This study aimed to assess knowledge, concerns, and vaccine acceptance toward Mpox among university students in North and Northeast China. A cross-sectional study was conducted among 3831 university students from seven universities in North and Northeast China between September 10 and September 25, 2023. This study found a relative insufficiency in Mpox knowledge among university students (71.60%), with less than half expressing concern about the Mpox outbreak (39.57%), and the majority exhibiting a positive attitude to vaccination (76.30%). Multivariate regression analysis revealed that a good knowledge level was associated with age, study discipline, education level, and a high level of concern about Mpox. Male, elderly, or highly educated participants had a low level of concern about Mpox. Participants with a high level of knowledge toward Mpox were more likely to have the vaccination willingness. This study might help governments and schools to understand students' Mpox perceptions and vaccination intentions, enabling them to implement effective measures in addressing the issue of inadequate understanding regarding Mpox among university students.

The global patent landscape of emerging infectious disease monkeypox.

BACKGROUND: Monkeypox is an emerging infectious disease with confirmed cases and deaths in several parts of the world. In light of this crisis, this study aims to analyze the global knowledge pattern of monkeypox-related patents and explore current trends and future technical directions in the medical development of monkeypox to inform research and policy. METHODS: A comprehensive study of 1,791 monkeypox-related patents worldwide was conducted using the Derwent patent database by descriptive statistics, social network method and linear regression analysis. RESULTS: Since the 21st century, the number of monkeypox-related patents has increased rapidly, accompanied by increases in collaboration between commercial and academic patentees. Enterprises contributed the most in patent quantity, whereas the initial milestone patent was filed by academia. The core developments of technology related to the monkeypox include biological and chemical medicine. The innovations of vaccines and virus testing lack sufficient patent support in portfolios. CONCLUSIONS: Monkeypox-related therapeutic innovation is geographically limited with strong international intellectual property right barriers though it has increased rapidly in recent years. The transparent licensing of patent knowledge is driven by the merger and acquisition model, and the venture capital, intellectual property and contract research organization model. Currently, the patent thicket phenomenon in the monkeypox field may slow the progress of efforts to combat monkeypox. Enterprises should pay more attention to the sharing of technical knowledge, make full use of drug repurposing strategies, and promote innovation of monkeypox-related technology in hotspots of antivirals (such as tecovirimat, cidofovir, brincidofovir), vaccines (JYNNEOS, ACAM2000), herbal medicine and gene therapy.

The 5 C model and Mpox vaccination behavior in Germany: a cross-sectional survey.

BACKGROUND: Due to the authorization of the Mpox vaccines, we aimed to identify determinants of the intention to get vaccinated, actively trying to receive vaccination, and for successfully receiving a vaccination in Germany employing the 5 C model of vaccination readiness. METHODS: Data stem from a cross-sectional online survey that was available online from August 13, 2022 to August 31, 2022. To assess the influence of the 5 C Model on vaccination behavior, we conducted a multinomial logistic regression. RESULTS: 3,338 participants responded to the survey, with 487 already vaccinated and 2,066 intending to receive a vaccination. Confidence and collective responsibility were positively associated with intention to get vaccinated, while complacency was negatively correlated. A higher score on the calculation scale increased the odds of intention to receive vaccination but not with actively having tried to receive a vaccination. Fewer perceived constraints were associated with higher odds to be vaccinated. Patients in practices that focus on HIV treatment were more likely to intend to get vaccinated, to have tried to get vaccinated and to be vaccinated, regardless of indication. While level of education had no impact, having an indication to get vaccinated was a strong predictor of vaccination behavior in all groups. CONCLUSION: Future vaccination campaigns should aim to reduce specific constraints of the target group and make vaccines widely available in primary care institutions beyond HIV-focused practices.

Synergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection.

The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity against smallpox and related orthopoxviruses like Monkeypox virus gradually declines, highlighting the need for efficient countermeasures not only for the prevention, but also for the treatment of already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates. Two mAbs, MV33 and EV42, targeting the two infectious forms of the virus, were selected for in vivo evaluation, based on their in vitro neutralization potency. A single dose of either MV33 or EV42 administered three days post-infection (dpi) to BALB/c female mice provides full protection against lethal ectromelia virus challenge. Importantly, a combination of both mAbs confers full protection even when provided five dpi. Whole-body bioimaging and viral load analysis reveal that combination of the two mAbs allows for faster and more efficient clearance of the virus from target organs compared to either MV33 or EV42 separately. The combined mAbs treatment further confers post-exposure protection against the currently circulating Monkeypox virus in Cast/EiJ female mice, highlighting their therapeutic potential against other orthopoxviruses.

Scenarios of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data from the Netherlands, 2022.

BackgroundFollowing the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks.AimWe combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate scenarios of future mpox outbreaks among men who have sex with men (MSM).MethodsSerum samples were obtained from 1,065 MSM attending Centres for Sexual Health (CSH) in Rotterdam or Amsterdam following the peak of the Dutch mpox outbreak and the introduction of vaccination. For MSM visiting the Rotterdam CSH, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)-specific IgG. These observations were combined with published data on serial interval and vaccine effectiveness to inform a stochastic transmission model that estimates the risk of future mpox outbreaks.ResultsThe seroprevalence of VACV-specific antibodies was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Transmission modelling showed that the impact of risk group vaccination on the original outbreak was likely small. However, assuming different scenarios, the number of mpox cases in a future outbreak would be markedly reduced because of vaccination. Simultaneously, the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis is a key component of any strategy to prevent new outbreaks.ConclusionOur findings indicate a reduced likelihood of large future mpox outbreaks among MSM in the Netherlands under current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities and disease awareness.

Monkeypox: A re-emerging disease.

ABSTRACT: The virus known as monkeypox is the source of the zoonotic disease monkeypox, which was historically widespread in Central Africa and West Africa. The cases of monkeypox in humans are uncommon outside of West and Central Africa, but copious nonendemic nations outside of Africa have recently confirmed cases. People when interact with diseased animals, then, they may inadvertently contact monkeypox. There are two drugs in the market: brincidofovir and tecovirimat and both of these drugs are permitted for the cure of monkeypox by the US Food and Drug Administration. The present review summarizes the various parameters of monkeypox in context with transmission, signs and symptoms, histopathological and etiological changes, and possible treatment. Monkeypox is clinically similar to that of smallpox infection but epidemiologically, these two are different, the present study also signifies the main differences and similarities of monkeypox to that of other infectious diseases. As it is an emerging disease, it is important to know about the various factors related to monkeypox so as to control it on a very early stage of transmission.

Mpox Diagnosis, Behavioral Risk Modification, and Vaccination Uptake among Gay, Bisexual, and Other Men Who Have Sex with Men, United Kingdom, 2022.

During the 2022 multicountry mpox outbreak, the United Kingdom identified cases beginning in May. UK cases increased in June, peaked in July, then rapidly declined after September 2022. Public health responses included community-supported messaging and targeted mpox vaccination among eligible gay, bisexual, and other men who have sex with men (GBMSM). Using data from an online survey of GBMSM during November-December 2022, we examined self-reported mpox diagnoses, behavioral risk modification, and mpox vaccination offer and uptake. Among 1,333 participants, only 35 (2.6%) ever tested mpox-positive, but 707 (53%) reported behavior modification to avoid mpox. Among vaccine-eligible GBMSM, uptake was 69% (95% CI 65%-72%; 601/875) and was 92% (95% CI 89%-94%; 601/655) among those offered vaccine. GBMSM self-identifying as bisexual, reporting lower educational qualifications, or identifying as unemployed were less likely to be vaccinated. Equitable offer and provision of mpox vaccine are needed to minimize the risk for future outbreaks and mpox-related health inequalities.

DeepSeq2Drug: An expandable ensemble end-to-end anti-viral drug repurposing benchmark framework by multi-modal embeddings and transfer learning.

Drug repurposing is promising in multiple scenarios, such as emerging viral outbreak controls and cost reductions of drug discovery. Traditional graph-based drug repurposing methods are limited to fast, large-scale virtual screens, as they constrain the counts for drugs and targets and fail to predict novel viruses or drugs. Moreover, though deep learning has been proposed for drug repurposing, only a few methods have been used, including a group of pre-trained deep learning models for embedding generation and transfer learning. Hence, we propose DeepSeq2Drug to tackle the shortcomings of previous methods. We leverage multi-modal embeddings and an ensemble strategy to complement the numbers of drugs and viruses and to guarantee the novel prediction. This framework (including the expanded version) involves four modal types: six NLP models, four CV models, four graph models, and two sequence models. In detail, we first make a pipeline and calculate the predictive performance of each pair of viral and drug embeddings. Then, we select the best embedding pairs and apply an ensemble strategy to conduct anti-viral drug repurposing. To validate the effect of the proposed ensemble model, a monkeypox virus (MPV) case study is conducted to reflect the potential predictive capability. This framework could be a benchmark method for further pre-trained deep learning optimization and anti-viral drug repurposing tasks. We also build software further to make the proposed model easier to reuse. The code and software are freely available at http://deepseq2drug.cs.cityu.edu.hk.

The successful treatment of mpox with brincidofovir in renal transplant recipients-a report of 2 cases.

An mpox outbreak was declared in July 2022 by the world health organization (WHO). It causes a mild self-limiting disease however; in immunosuppressed hosts, it tends to cause severe disseminated infection. Most cases of mpox in sold organ transplant (SOT) recipients reported in the literature were treated with tecovirimat. Here we report two cases of severe disseminated mpox infection in renal transplant recipients that were successfully treated with brincidofovir. Both patients were discharged from the hospital with no immediate significant side effects from brincidofovir reported until the submission of this report.

Underdetected dispersal and extensive local transmission drove the 2022 mpox epidemic.

The World Health Organization declared mpox a public health emergency of international concern in July 2022. To investigate global mpox transmission and population-level changes associated with controlling spread, we built phylogeographic and phylodynamic models to analyze MPXV genomes from five global regions together with air traffic and epidemiological data. Our models reveal community transmission prior to detection, changes in case reporting throughout the epidemic, and a large degree of transmission heterogeneity. We find that viral introductions played a limited role in prolonging spread after initial dissemination, suggesting that travel bans would have had only a minor impact. We find that mpox transmission in North America began declining before more than 10% of high-risk individuals in the USA had vaccine-induced immunity. Our findings highlight the importance of broader routine specimen screening surveillance for emerging infectious diseases and of joint integration of genomic and epidemiological information for early outbreak control.

Lot-to-lot consistency, immunogenicity, and safety of the Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccine regimen: A phase 3, randomized, double-blind, placebo-controlled trial.

This phase-3, double-blind, placebo-controlled study (NCT04228783) evaluated lot-to-lot consistency of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen. Participants were randomized (6:6:6:1) to receive the two-dose regimen from three consecutively manufactured lots of Ad26.ZEBOV on Day 1 paired with three consecutively manufactured lots of MVA-BN-Filo on Day 57 (Groups 1-3) or two doses of placebo (Group 4). An additional cohort also received an Ad26.ZEBOV booster or placebo 4 months post-dose 2. Equivalence of the immunogenicity at 21 days post-dose 2 between any two groups was demonstrated if the 95% confidence interval (CI) of the Ebola virus glycoprotein (EBOV GP)-binding antibody geometric mean concentration (GMC) ratio was entirely within the prespecified margin of 0.5-2.0. Lot-to-lot consistency (i.e., consecutive lots can be consistently manufactured) was accomplished if equivalence was shown for all three pairwise comparisons. Results showed that the primary objective in the per-protocol immunogenicity subset (n = 549) was established for each pairwise comparison (Group 1 vs 2: GMC ratio = 0.9 [95% CI: 0.8, 1.1], Group 1 vs 3: 0.9 [0.8, 1.1], Group 2 vs 3: 1.0 [0.9, 1.2]). Equivalence of the three groups for the Ad26.ZEBOV component only was also demonstrated at 56 days post-dose 1. EBOV GP-binding antibody responses (post-vaccination concentrations >2.5-fold from baseline) were observed in 419/421 (99.5%) vaccine recipients at 21 days post-dose 2 and 445/460 (96.7%) at 56 days post-dose 1. In the booster cohort (n = 39), GMCs increased 9.0- and 11.8-fold at 7 and 21 days post-booster, respectively, versus pre-booster. Ad26.ZEBOV, MVA-BN-Filo was well tolerated, and no safety issues were identified.

Prolonged viral shedding in an immunocompromised Korean patient infected with hMPXV, sub-lineage B.1.3, with acquired drug resistant mutations during tecovirimat treatment.

Following the worldwide surge in mpox (monkeypox) in 2022, cases have persisted in Asia, including South Korea, and sexual contact is presumed as the predominant mode of transmission, with a discernible surge in prevalence among immunocompromised patients. Drugs such as tecovirimat can result in drug-resistant mutations, presenting obstacles to treatment. This study aimed to ascertain the presence of tecovirimat-related resistant mutations through genomic analysis of the monkeypox virus isolated from a reported case involving prolonged viral shedding in South Korea. Here, tecovirimat-resistant mutations, previously identified in the B.1 clade, were observed in the B.1.3 clade, predominant in South Korea. These mutations exhibited diverse patterns across different samples from the same patient and reflected the varied distribution of viral subpopulations in different anatomical regions. The A290V and A288P mutant strains we isolated hold promise for elucidating these mechanisms, enabling a comprehensive analysis of viral pathogenesis, replication strategies, and host interactions. Our findings imply that acquired drug-resistant mutations, may present a challenge to individual patient treatment. Moreover, they have the potential to give rise to transmitted drug-resistant mutations, thereby imposing a burden on the public health system. Consequently, the meticulous genomic surveillance among immunocompromised patients, conducted in this research, assumes paramount importance.

A theory-based assessment of mpox: Findings from a nationally representative survey of U.S. adults.

The purpose of this research was to examine individual differences related to fear of, perceived susceptibility to, and perceived severity of mpox as well as mpox knowledge, fear, perceived susceptibility, and perceived severity as predictors of vaccine intention in a national survey of U.S. adults (aged ≥18 years). Address-based sampling (ABS) methods were used to ensure full coverage of all households in the nation, reflecting the 2021 March Supplement of the Current Population Survey. Internet-based surveys were self-administered by Ipsos between September 16-26, 2022. N = 1018 participants completed the survey. The survey included items, based partially on the Health Belief Model, assessing vaccine intention (1 item; responses from 1 [Definitely not] to 5 [Definitely]), fear of mpox (7-item scale; α = .89; theoretical mean = 7-35), perceived susceptibility to mpox (3-item scale; α = .85; theoretical mean = 3-15), and perceived severity of mpox (4-item scale; α = .65; theoretical mean = 4-20). Higher scores indicate greater fear, susceptibility, and severity. One-way ANOVAs were run to examine mean score differences by demographic groups (e.g., gender, race/ethnicity, sexual orientation), and multiple regression analyses assessed the relationship between predictors (mpox knowledge, susceptibility/severity, fear) and a single outcome (vaccination intention), while controlling for demographic covariates. Sampling weights were applied to all analyses. Only 1.8% (n = 18) of respondents reported having received the mpox vaccine. While mpox vaccine intention was low (M = 2.09, SD = 0.99), overall differences between racial/ethnic, sexual orientation, education, and household income groups were statistically significant. Fear of mpox was very low (M = 13.13, SD = 5.33), and there were overall statistically significant differences in both fear and perceived severity among gender, race/ethnicity, sexual orientation, education, and household income groups. While respondents reported not feeling very susceptible to mpox (M = 5.77, SD = 2.50), they generally rated mpox as just above the theoretical mean in terms of severity (M = 11.01, SD = 2.85). Mpox knowledge, fear, severity, and susceptibility, as well as race/ethnicity, were all statistically significant predictors of intention to vaccinate, with susceptibility representing the strongest predictor. Overall, Americans' vaccination for mpox/vaccine intent was low. Gay/lesbian and racial/ethnic minority respondents felt more susceptible to and viewed mpox more severely, compared with heterosexual and White respondents, respectively. These data may be used to tailor risk and prevention (e.g., vaccination) interventions, as cases continue to surge in the current global mpox outbreak. Greater perceptions of susceptibility, severity, and fear about mpox exist largely among minority populations. While public health messaging to promote mpox vaccination can focus on improving knowledge, as well as addressing fear and perceived severity of, and susceptibility to, mpox, such messages should be carefully crafted to prevent disproportionate negative effects on marginalized communities.

Adverse Reactions After Intradermal Vaccination With JYNNEOS for Mpox in Korea.

In response to the Mpox domestic epidemic, South Korea initiated a nationwide vaccination program in May 2023, administering a 0.1 mL intradermal dose of JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to a high-risk group. To investigate the adverse reactions after intradermal JYNNEOS vaccination, an anonymous online survey was conducted at the National Medical Center from May 22 to July 31, 2023. Overall, 142 individuals responded. Over 80% of the respondents reported local reactions of predominantly mild severity. The predominant local reactions were pruritus, redness, and swelling; their incidence rates after the first dose were 66.2%, 48.1%, and 49.4%, respectively; the corresponding rates after the second dose were 69.2%, 60.6%, and 53.8%. Fewer respondents reported systemic symptoms. The most common systemic symptom was fatigue, the incidence rates of which after the first and second doses were 37.7% and 24.6%, respectively. Overall, the intradermally administered JYNNEOS vaccine appeared well tolerated.

An overview on mRNA-based vaccines to prevent monkeypox infection.

The human monkeypox virus (Mpox) is classified as a member of the Poxviridae family and belongs to the Orthopoxvirus genus. Mpox possesses double-stranded DNA, and there are two known genetic clades: those originating in West Africa and the Congo Basin, commonly known as Central African clades. Mpox may be treated with either the vaccinia vaccination or the therapeutics. Modifying the smallpox vaccine for treating and preventing Mpox has shown to be beneficial because of the strong link between smallpox and Mpox viruses and their categorization in the same family. Cross-protection against Mpox is effective with two Food and Drug Administration (FDA)-approved smallpox vaccines (ACAM2000 and JYNNEOSTM). However, ACAM2000 has the potential for significant adverse effects, such as cardiac issues, whereas JYNNEOS has a lower risk profile. Moreover, Mpox has managed to resurface, although with modified characteristics, due to the discontinuation and cessation of the smallpox vaccine for 40 years. The safety and efficacy of the two leading mRNA vaccines against SARS-CoV-2 and its many variants have been shown in clinical trials and subsequent data analysis. This first mRNA treatment model involves injecting patients with messenger RNA to produce target proteins and elicit an immunological response. High potency, the possibility of safe administration, low-cost manufacture, and quick development is just a few of the benefits of RNA-based vaccines that pave the way for a viable alternative to conventional vaccines. When protecting against Mpox infection, mRNA vaccines are pretty efficient and may one day replace the present whole-virus vaccines. Therefore, the purpose of this article is to provide a synopsis of the ongoing research, development, and testing of an mRNA vaccine against Mpox.

Mpox virus Clade IIb infected Cynomolgus macaques via mimic natural infection routes closely resembled human mpox infection.

Generating an infectious non-human primate (NHP) model using a prevalent monkeypox virus (MPXV) strain has emerged as a crucial strategy for assessing the efficacy of vaccines and antiviral drugs against human MPXV infection. Here, we established an animal model by infecting cynomolgus macaques with the prevalent MPXV strain, WIBP-MPXV-001, and simulating its natural routes of infection. A comprehensive analysis and evaluation were conducted on three animals, including monitoring clinical symptoms, collecting hematology data, measuring viral loads, evaluating cellular and humoral immune responses, and examining histopathology. Our findings revealed that initial skin lesions appeared at the inoculation sites and subsequently spread to the limbs and back, and all infected animals exhibited bilateral inguinal lymphadenopathy, eventually leading to a self-limiting disease course. Viral DNA was detected in post-infection blood, nasal, throat, rectal and blister fluid swabs. These observations indicate that the NHP model accurately reflects critical clinical features observed in human MPXV infection. Notably, the animals displayed clinical symptoms and disease progression similar to those of humans, rather than a lethal outcome as observed in previous studies. Historically, MPXV was utilized as a surrogate model for smallpox. However, our study contributes to a better understanding of the dynamics of current MPXV infections while providing a potential infectious NHP model for further evaluation of vaccines and antiviral drugs against mpox infection. Furthermore, the challenge model closely mimics the primary natural routes of transmission for human MPXV infections. This approach enhances our understanding of the precise mechanisms underlying the interhuman transmission of MPXV.

Human monkeypox virus: Epidemiologic review and research progress in diagnosis and treatment.

Monkeypox virus (MPXV) is responsible for causing a zoonotic disease called monkeypox (mpox), which sporadically infects humans in West and Central Africa. It first infected humans in 1970 and, along with the variola virus, belongs to the genus Orthopoxvirus in the poxvirus family. Since the World Health Organization declared the MPXV outbreak a "Public Health Emergency of International Concern" on July 23, 2022, the number of infected patients has increased dramatically. To control this epidemic and address this previously neglected disease, MPXV needs to be better understood and reevaluated. In this review, we cover recent research on MPXV, including its genomic and pathogenic characteristics, transmission, mutations and mechanisms, clinical characteristics, epidemiology, laboratory diagnosis, and treatment measures, as well as prevention of MPXV infection in light of the 2022 and 2023 global outbreaks. The 2022 MPXV outbreak has been primarily associated with close intimate contact, including sexual activity, with most cases diagnosed among men who have sex with men. The incubation period of MPXV infection usually lasts from 6 to 13 days, and symptoms include fever, muscle pains, headache, swollen lymph nodes, and a characteristic painful rash, including several stages, such as macules, papules, blisters, pustules, scabs, and scab shedding involving the genitals and anus. Polymerase chain reaction (PCR) is usually used to detect MPXV in skin lesion material. Treatment includes supportive care, antivirals, and intravenous vaccinia immune globulin. Smallpox vaccines have been designed with four givens emergency approval for use against MPXV infection.