Effectiveness of modified vaccinia Ankara-Bavarian Nordic vaccine against mpox infection: emulation of a target trial.

OBJECTIVE: To estimate the real world effectiveness of modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine against mpox infection. DESIGN: Emulation of a target trial. SETTING: Linked databases in Ontario, Canada. PARTICIPANTS: 9803 men aged ≥18 years with a history of being tested for syphilis and a laboratory confirmed bacterial sexually transmitted infection (STI) in the previous year, or who filled a prescription for HIV pre-exposure prophylaxis in the previous year. On each day between 12 June 2022 and 27 October 2022, those who had been vaccinated 15 days previously were matched 1:1 with unvaccinated men by age, geographical region, past HIV diagnosis, number of bacterial STI diagnoses in the previous three years, and receipt of any non-MVA-BN vaccine in the previous year. MAIN OUTCOME MEASURE: The main outcome measure was vaccine effectiveness ((1-hazard ratio)×100) of one dose of subcutaneously administered MVA-BN against laboratory confirmed mpox infection. A Cox proportional hazards model was used to estimate hazard ratios to compare the rate of laboratory confirmed mpox between the two groups. RESULTS: 3204 men who received the vaccine were matched to 3204 unvaccinated controls. A total of 71 mpox infections were diagnosed, with 0.09 per 1000 person days (95% confidence interval (CI) 0.05 to 0.13) in the vaccinated group and 0.20 per 1000 person days (0.15 to 0.27) in the unvaccinated group over the study period of 153 days. Estimated vaccine effectiveness of one dose of MVA-BN against mpox infection was 58% (95% CI 31% to 75%). CONCLUSION: The findings of this study, conducted in the context of a targeted vaccination programme and evolving outbreak of mpox, suggest that one dose of MVA-BN is moderately effective in preventing mpox infection.

Global prevalence and determinants associated with the acceptance of monkeypox vaccination.

Assessing the acceptance of the monkeypox vaccine is crucial for the success of vaccination programs, yet the prevalence reports remain inconclusive. The aim of this study was to determine the global prevalence of monkeypox vaccine acceptance and identify its associated factors. A meta-analysis was conducted with a comprehensive search strategy on the following databases, including Scopus, Embase, and PubMed, for articles published up to April 5, 2024. This study utilizes a single-arm meta-analysis to calculate the pooled prevalence of monkeypox vaccine acceptance. A Z-test was employed to identify factors associated with the vaccine acceptance. Our study analyzed 51 articles encompassing 98,746 participants, revealing an overall monkeypox vaccine acceptance rate of 65%. Notably, the highest acceptance rates were observed among men who have sex with men (MSMs), while healthcare workers (HCWs) showed the lowest acceptance rates. Additionally, our findings indicated an increased acceptance in individuals with educational attainment beyond a bachelor's degree, a history of COVID-19 and influenza vaccination, homosexual orientation, and HIV-positive status. Conversely, lower acceptance risk was associated with those with educational attainment below a bachelor's degree, heterosexual orientation, and bisexual orientation. In conclusion, our current study has determined the rate of monkeypox vaccine acceptance and identified its associated factors. These findings offer valuable insights as the foundation for targeted policies to manage and increase acceptance rates.

Contact Tracing for Mpox Clade II Cases Associated with Air Travel - United States, July 2021-August 2022.

Monkeypox virus (MPXV) can spread among humans through direct contact with lesions, scabs, or saliva; via respiratory secretions; and indirectly from fomites; via percutaneous injuries; and by crossing the placenta to the fetus during pregnancy. Since 2022, most patients with mpox in the United States have experienced painful skin lesions, and some have had severe illness. During 2021-2022, CDC initiated aircraft contact investigations after receiving reports of travelers on commercial flights with probable or confirmed mpox during their infectious period. Data were collected 1) during 2021, when two isolated clade II mpox cases not linked to an outbreak were imported into the United States by international travelers and 2) for flights arriving in or traveling within the United States during April 30-August 2, 2022, after a global clade II mpox outbreak was detected in May 2022. A total of 113 persons (100 passengers and 13 crew members) traveled on 221 flights while they were infectious with mpox. CDC developed definitions for aircraft contacts based on proximity to mpox cases and flight duration, sent information about these contacts to U.S. health departments, and received outcome information for 1,046 (68%) of 1,538 contacts. No traveler was found to have acquired mpox via a U.S. flight exposure. For persons with mpox and their contacts who had departed from the United States, CDC forwarded contact information as well as details about the exposure event to destination countries to facilitate their own public health investigations. Findings from these aircraft contact investigations suggest that traveling on a flight with a person with mpox does not appear to constitute an exposure risk or warrant routine contact tracing activities. Nonetheless, CDC recommends that persons with mpox isolate and delay travel until they are no longer infectious.

Editorial: Reasons for Increasing Global Concerns for the Spread of Mpox.

On August 14, 2024, the Director General of the World Health Organization (WHO) declared that the increasing outbreaks of mpox (formerly monkeypox) should be regarded as an international public health emergency due to the growing number of cases in endemic and non-endemic geographical areas, and increasing disease severity. The latest update from the WHO and the alerts given regarding the status of mpox follows an upsurge in the incidence and severity of mpox in the Democratic Republic of the Congo (DRC) and an increasing number of African countries, with spread to other continents and countries This Editorial aims to provide an update on the current status of mpox and includes reasons for the increasing global concerns for the spread of the mpox virus (MPXV).

Development and validation of the mpox stigma scale (MSS) and mpox knowledge scale (MKS).

BACKGROUND: Few validated brief scales are available to measure constructs that may hinder mpox-related prevention and care engagement, such as knowledge and stigma. Both are highly salient barriers to infectious disease care and disease understanding, precursors to evaluating one's risk and need to, for example, accept vaccination. To address this gap, we developed and validated the Mpox Stigma Scale (MSS) and Mpox Knowledge Scale (MKS). METHODS: As part of a full-scale clinical trial, we offered an optional mpox survey to participants who self-identified as African American or Black, were 18-29 years old, and lived in Alabama, Georgia, or North Carolina (2023, N = 330). We calculated psychometric properties through confirmatory factor analyses (CFA) and applied Comparative Fit Index (CFI), Goodness of Fit Index (GFI), and Tucker-Lewis Index (TLI) values equal to or exceeding 0.90 and Root Mean Square Error of Approximation (RMSEA) and Standardized Root Mean Square Residual (SRMR) values less than 0.08 to determine adequate model fit. We computed internal reliability using Cronbach's alpha and calculated Pearson or Spearman correlation coefficients between the MSS and MKS and related variables. RESULTS: For the MSS, CFA results showed that the one-factor model fit the data well (χ2(df = 5, N = 330) = 34.962, CFI = 0.97, GFI = 0.99, TLI = 0.94, RMSEA = 0.13, SRMR = 0.03). For the MKS, the one-factor model provided a good fit to the data (χ2(df = 6, N = 330) = 8.44, CFI = 0.99, GFI = 0.99, TLI = 0.95, RMSEA = 0.15, SRMR = 0.02). Cronbach's alphas were MSS = 0.91 and MKS = 0.83, suggesting good to excellent reliability. The MSS was correlated with the MKS (r = .55, p < .001), stigmatizing attitudes (r = .24, p < .001), attitudes towards mpox vaccination (r=-.12, p = .030), and worry about contracting mpox (r = .44, p < .001). The MKS was correlated with worry about contracting mpox (r = .30, p < .001) and mpox disclosure (r=-.16, p = .003). CONCLUSIONS: The MSS and MKS are reliable and valid tools for public health practice, treatment and prevention research, and behavioral science. Further validation is warranted across populations and geographic locations. TRIAL REGISTRATION: ClinicalTrials.gov NCT05490329.

Monkeypox pandemic in Sudan, surveillance epidemiologic report, 2022.

BACKGROUND: Mpox, is a zoonosis that is known to be endemic in several Central and West African countries. Recently, in 2022, it has emerged in Europe and United States, what raised the alarm to be declared in late June 2024 as a public health event of international concern. This study aimed to give insight about the recent spread of mpox in Sudan, and documents the epidemiologic situation. METHODS: Through a cross-sectional design, Sudan mpox data was extracted from the disease surveillance line-list at the national level at Sudan Federal Ministry of Health. the data was customized and then analyzed using Epi Info7 software. Analysis was done using frequencies and percentages and the results presented in tables and figures. Permission and ethical approval were obtained from the Health Emergency and Epidemic Control Directorate at the Federal Ministry of Health. RESULTS: The outbreak of mpox was confirmed after testing of initial specimens outside Sudan with positivity rate of 72%. Later the cases continued to be reported based on the clinical diagnosis and standard case definition. Out of 375 reported cases, 54.4% were males, while 45.6% were females. The age of cases ranged from one month to 78 years with majority (41.1%) of the cases were children under 5 years of age. Regarding the reported symptoms, all cases had the characteristic skin rash and 74.1% of them had fever. Other symptoms included, headache (31.5%), sore throat (30.9%) and lymphadenopathy (26.1%). For occupation, 35.7% were preschool and 10.4% were school children, 9% of cases were prisoners. Around 22 (5.8%) reported contact history with a confirmed case, while (5.6%) of the cases were imported cases. Cases were reported from 17 states with 42 affected localities (districts) with an overall attack rate of 2.36/ 100,000. The highest number of cases was reported from Gadaref (45.3%), West Darfur (25.9%), Khartoum (13.3%) and north Darfur (3.5%). In Gadaref, 146 (85.8%) of the cases were from a refugees' camp. Started in epi week 19, the outbreak peaked in week 38 and last in week 42. CONCLUSION: Mpox was confirmed in the new Sudan for the first time with cases reported in most of states. Although importation of the virus is hypothesized, internal hidden circulation is possible and more in-depth investigation is highly recommended. The higher rate of infection among preschool, school children and refugees, highlights the need to strengthen the prevention and control measures in schools and camps. More focus on the data completeness is required for better understanding of the disease and can be ensured by the surveillance directorate through training of staff and updating of reporting forms. Strengthening the lab capacity inside the country is a necessity to ensure testing of all the clinically diagnosed cases.

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.

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.

The transmission dynamics of an infectious disease model in fractional derivative with vaccination under real data.

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.

Rapid regional mobile laboratory response and genomic monkeypox virus (MPXV) surveillance in seven East African Community partner states, August 2024: preparedness activities for the ongoing outbreak.

The East African Community (EAC) is experiencing an unprecedented, emerging mpox outbreak since July 2024 in five of eight partner states. We highlight rapid regional response measures, initiated August 2024 coordinated by EAC: field deployment of six mobile laboratories in Burundi, Rwanda, Uganda, Tanzania, Kenya, South Sudan to high-risk areas, donation of one mobile laboratory to Democratic Republic of the Congo and genomic monkeypox virus (MPXV) surveillance support. These interventions aim to limit local mpox spread and support international containment.

Effectiveness of historical smallpox vaccination against mpox clade II in men in Denmark, France, the Netherlands and Spain, 2022.

BackgroundIn 2022, a global monkeypox virus (MPXV) clade II epidemic occurred mainly among men who have sex with men. Until early 1980s, European smallpox vaccination programmes were part of worldwide smallpox eradication efforts. Having received smallpox vaccine > 20 years ago may provide some cross-protection against MPXV.AimTo assess the effectiveness of historical smallpox vaccination against laboratory-confirmed mpox in 2022 in Europe.MethodsEuropean countries with sufficient data on case vaccination status and historical smallpox vaccination coverage were included. We selected mpox cases born in these countries during the height of the national smallpox vaccination campaigns (latest 1971), male, with date of onset before 1 August 2022. We estimated vaccine effectiveness (VE) and corresponding 95% CI for each country using logistic regression as per the Farrington screening method. We calculated a pooled estimate using a random effects model.ResultsIn Denmark, France, the Netherlands and Spain, historical smallpox vaccination coverage was high (80-90%) until the end of the 1960s. VE estimates varied widely (40-80%, I2 = 82%), possibly reflecting different booster strategies. The pooled VE estimate was 70% (95% CI: 23-89%).ConclusionOur findings suggest residual cross-protection by historical smallpox vaccination against mpox caused by MPXV clade II in men with high uncertainty and heterogeneity. Individuals at high-risk of exposure should be offered mpox vaccination, following national recommendations, regardless of prior smallpox vaccine history, until further evidence becomes available. There is an urgent need to conduct similar studies in sub-Saharan countries currently affected by the MPXV clade I outbreak.

Equivalence of freeze-dried and liquid-frozen formulations of MVA-BN as smallpox and mpox vaccine.

Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) as a smallpox and mpox vaccine has been approved in its liquid-frozen (LF) formulation in the US, Canada, and EU. A freeze-dried (FD) formulation may offer additional benefits, such as a longer shelf life and reduced dependence on cold chain storage and transport. In a phase 2 clinical trial, 651 vaccinia-naïve participants were vaccinated with two doses of MVA-BN LF or FD, 4 weeks apart. The objectives were to compare MVA-BN FD with LF in terms of vaccine-induced immune responses, safety, and reactogenicity. Non-inferiority of the immune response was assessed by the 95% CI of the geometric mean ratios. Both formulations induced robust vaccinia-specific humoral and cellular immune responses. At peak humoral responses (Week 6), geometric means of total antibody titers were 1096 (95% CI 1013, 1186) from the FD group and 877 (95% CI 804, 956) from the LF group, achieving the primary endpoint of non-inferiority of MVA-BN FD compared to MVA-BN LF. At peak cellular responses (Week 2), geometric means of T cell spot forming units were 449 (95% CI 341, 590) from the FD group and 316 (95% CI 234, 427) from the LF group. Both formulations of MVA-BN were well tolerated, with similar unsolicited AEs and solicited systemic reactions in both groups but slightly more local reactions in the FD group. No vaccine-related serious adverse events (SAEs) or vaccine-related AE of special interest were reported. The FD formulation of MVA-BN was shown to be equivalent to MVA-BN LF.