Updating Reproduction Number Estimates for Mpox in the Democratic Republic of Congo Using Surveillance Data.

Incidence of human monkeypox (mpox) has been increasing in West and Central Africa, including in the Democratic Republic of Congo (DRC), where monkeypox virus (MPXV) is endemic. Most estimates of the pathogen's transmissibility in the DRC are based on data from the 1980s. Amid the global 2022 mpox outbreak, new estimates are needed to characterize the virus' epidemic potential and inform outbreak control strategies. We used the R package vimes to identify clusters of laboratory-confirmed mpox cases in Tshuapa Province, DRC. Cases with both temporal and spatial data were assigned to clusters based on the disease's serial interval and spatial kernel. We used the size of the clusters to infer the effective reproduction number, Rt, and the rate of zoonotic spillover of MPXV into the human population. Out of 1,463 confirmed mpox cases reported in Tshuapa Province between 2013 and 2017, 878 had both date of symptom onset and a location with geographic coordinates. Results include an estimated Rt of 0.82 (95% CI: 0.79-0.85) and a rate of 132 (95% CI: 122-143) spillovers per year assuming a reporting rate of 25%. This estimate of Rt is larger than most previous estimates. One potential explanation for this result is that Rt could have increased in the DRC over time owing to declining population-level immunity conferred by smallpox vaccination, which was discontinued around 1982. Rt could be overestimated if our assumption of one spillover event per cluster does not hold. Our results are consistent with increased transmissibility of MPXV in Tshuapa Province.

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

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

Monkeypox virus: insights into pathogenesis and laboratory testing methods.

The monkeypox virus (MPXV) is a zoonotic pathogen that transmits between monkeys and humans, exhibiting clinical similarities with the smallpox virus. Studies on the immunopathogenesis of MPXV revealed that an initial strong innate immune response is elicited on viral infection that subsequently helps in circumventing the host defense. Once the World Health Organization (WHO) declared it a global public health emergency in July 2022, it became essential to clearly demarcate the MPXV-induced symptoms from other viral infections. We have exhaustively searched the various databases involving Google Scholar, PubMed, and Medline to extract the information comprehensively compiled in this review. The primary focus of this review is to describe the diagnostic methods for MPXV such as polymerase chain reaction (PCR), and serological assays, along with developments in viral isolation, imaging techniques, and next-generation sequencing. These innovative technologies have the potential to greatly enhance the accuracy of diagnostic procedures. Significant discoveries involving MPXV immunopathogenesis have also been highlighted. Overall, this will be a knowledge repertoire that will be crucial for the development of efficient monitoring and control strategies in response to the MPXV infection helping clinicians and researchers in formulating healthcare strategies.

Optimizing skin disease diagnosis: harnessing online community data with contrastive learning and clustering techniques.

Skin diseases pose significant challenges in China. Internet health forums offer a platform for millions of users to discuss skin diseases and share images for early intervention, leaving large amount of valuable dermatology images. However, data quality and annotation challenges limit the potential of these resources for developing diagnostic models. In this study, we proposed a deep-learning model that utilized unannotated dermatology images from diverse online sources. We adopted a contrastive learning approach to learn general representations from unlabeled images and fine-tuned the model on coarsely annotated images from Internet forums. Our model classified 22 common skin diseases. To improve annotation quality, we used a clustering method with a small set of standardized validation images. We tested the model on images collected by 33 experienced dermatologists from 15 tertiary hospitals and achieved a 45.05% top-1 accuracy, outperforming the published baseline model by 3%. Accuracy increased with additional validation images, reaching 49.64% with 50 images per category. Our model also demonstrated transferability to new tasks, such as detecting monkeypox, with a 61.76% top-1 accuracy using only 50 additional images in the training process. We also tested our model on benchmark datasets to show the generalization ability. Our findings highlight the potential of unannotated images from online forums for future dermatology applications and demonstrate the effectiveness of our model for early diagnosis and potential outbreak mitigation.

The first two case reports of confirmed Mpox in patients with syphilis in a dense urban setting, Can Tho, Vietnam: From clinical presentation, treatment, and epidemiological surveillance to prevention.

This report elucidated the first two noteworthy cases of Mpox that manifested as an emerging concern in a densely populated city in Vietnam. Two male patients (22 and 27 years old) were admitted to the hospital due to the presence of small pustules on their faces, accompanied by symptoms of fatigue, drowsiness, and muscle pain. Reverse transcription-polymerase chain reaction confirmed the presence of Mpox. The patients possessed a medical history involving four previous treatments for syphilis, a continuous antiretroviral regimen for over 3 years, no previous history of chickenpox, a lack of vaccination against chickenpox, and engagement in intimate contact with other men. Following a 14-day isolation period coupled with appropriate medical interventions, both patients exhibited stable health conditions, marked by the absence of fever and the desiccation of skin blisters. Subsequently, they were discharged with instructions for ongoing health monitoring. Comprehensive surveillance and monitoring approaches have been implemented for all individuals in close contact with the affected patients, adhering to established guidelines. Notably, no suspected cases have been identified during the current surveillance efforts. The collective findings underscore the significance of robust surveillance, continuous monitoring, and strategic vaccination initiatives, particularly in densely populated urban centers, to effectively manage and mitigate the impact of Mpox outbreaks.

Case report: atypical presentation of mpox with massive hematochezia and prolonged viral shedding despite tecovirimat treatment.

BACKGROUND: The outbreak of mpox that occurred between 2022 and 2023 is primarily being transmitted through sexual contact. As of now, there is no consensus on the recommended duration of isolation to prevent sexual transmission of the virus. Moreover, this particular mpox outbreak has presented with distinct complications in comparison to previous occurrences. In this report, we present a case involving severe rectal bleeding from an ulcer in a mpox patient with a history of engaging in receptive sexual contact. CASE PRESENTATION: A 30-year-old Korean man presented at the hospital with complaints of fever, multiple skin lesions, and anal pain. Monkeypox virus polymerase chain reaction (PCR) results were positive for skin lesions on the penis and wrist. The patient received a 12-day course of tecovirimat due to anal symptoms and perianal skin lesions. Following isolation for 12 days and after all skin scabs had naturally fallen off, with no new skin lesions emerging for a consecutive 48 hours-conforming to the criteria of the Korean Disease Control and Prevention Agency-the patient was discharged. However, 1 day after discharge, the patient returned to the hospital due to hematochezia. His hemoglobin level had significantly dropped from 14.0 g/dL to 8.2 g/dL. Sigmoidoscopy unveiled a sizable rectal ulceration with exposed blood vessels, prompting the application of hemostasis through metal clipping. Subsequent monkeypox virus real-time PCR conducted on rectal tissue and swabs yielded positive results (with cycle threshold values of 28.48 and 31.23, respectively). An abdominal CT scan exposed a perirectal abscess, for which ampicillin-sulbactam was administered. CONCLUSION: This case underscores the importance of monitoring for bleeding complications and confirming the resolution of rectal lesions before discharging patients from isolation, particularly in cases where patients have a history of engaging in receptive sexual contact with men or are presenting with anal symptoms.

Proctitis: An Approach to the Symptomatic Patient.

Proctitis is an inflammatory condition of the distal rectum that can be associated with common sexually transmitted infections (STIs), such as gonorrhea, chlamydia, and syphilis. For persons presenting with ulcerative findings on examination, in addition to syphilis, Mpox, lymphogranuloma venereum, and herpes simplex virus should be in the differential. Providers should also be aware that there are evolving data to support a role for Mycoplasma genitalium in proctitis. Performing a comprehensive history, clinical evaluation including anoscopy, and rectal nucleic amplification STI testing may be useful in identifying the cause of proctitis and targeting treatment.

Lessons Learned From Implementation of Mpox Surveillance During an Outbreak Response in Tennessee, 2022.

OBJECTIVES: Mpox surveillance was integral during the 2022 outbreak response. We evaluated implementation of mpox surveillance in Tennessee during an outbreak response and made recommendations for surveillance during emerging infectious disease outbreaks. METHODS: To understand surveillance implementation, system processes, and areas for improvement, we conducted 8 semistructured focus groups and 7 interviews with 36 health care, laboratory, and health department representatives during September 9-20, 2022. We categorized and analyzed session transcription and notes. We analyzed completeness and timeliness of surveillance data, including 349 orthopoxvirus-positive laboratory reports from commercial, public health, and health system laboratories during July 1-August 31, 2022. RESULTS: Participants described an evolving system and noted that existing informatics platforms inefficiently supported iterations of reporting requirements. Clear communication, standardization of terminology, and shared, adaptable, and user-friendly informatics platforms were prioritized for future emerging infectious disease surveillance systems. Laboratory-reported epidemiologic information was often incomplete; only 55% (191 of 349) of reports included patient address and telephone number. The median time from symptom onset to specimen collection was 5 days (IQR, 3-6 d), from specimen collection to laboratory reporting was 3 days (IQR, 1-4 d), from laboratory reporting to patient interview was 1 day (IQR, 1-3 d), and from symptom onset to patient interview was 9 days (IQR, 7-12 d). CONCLUSIONS: Future emerging infectious disease responses would benefit from standardized surveillance approaches that facilitate rapid implementation. Closer collaboration among informatics, laboratory, and clinical partners across jurisdictions and agencies in determining system priorities and designing workflow processes could improve flexibility of the surveillance platform and completeness and timeliness of laboratory reporting. Improved timeliness will facilitate public health response and intervention, thereby mitigating morbidity.

Detecting Mpox Cases Through Wastewater Surveillance - United States, August 2022-May 2023.

In October 2022, CDC's National Wastewater Surveillance System began routine testing of U.S. wastewater for Monkeypox virus. Wastewater surveillance sensitivity, positive predictive value (PPV), and negative predictive value (NPV) for Monkeypox virus were evaluated by comparing wastewater detections (Monkeypox virus detected versus not detected) to numbers of persons with mpox in a county who were shedding virus. Case ascertainment was assumed to be complete, and persons with mpox were assumed to shed virus for 25 days after symptom onset. A total of 281 cases and 3,492 wastewater samples from 89 sites in 26 counties were included in the analysis. Wastewater surveillance in a single week, from samples representing thousands to millions of persons, had a sensitivity of 32% for detecting one or more persons shedding Monkeypox virus, 49% for detecting five or more persons shedding virus, and 77% for detecting 15 or more persons shedding virus. Weekly PPV and NPV for detecting persons shedding Monkeypox virus in a county were 62% and 80%, respectively. An absence of detections in counties with wastewater surveillance signified a high probability that a large number of cases were not present. Results can help to guide the public health response to Monkeypox virus wastewater detections. A single, isolated detection likely warrants a limited public health response. An absence of detections, in combination with no reported cases, can give public health officials greater confidence that no cases are present. Wastewater surveillance can serve as a useful complement to case surveillance for guiding the public health response to an mpox outbreak.

[Survey on monkeypox knowledge awareness, risk perception and vaccination intention in men who have sex with men in five cities in northeast China].

Objective: To understand the monkeypox knowledge awareness, risk perception and vaccination intention in men who have sex with men (MSM) in five cities in northeast China. Methods: A cross-sectional study was conducted by using electronic questionnaire in MSM selected by convenience sampling in five cities in northeast China (Shenyang, Panjin, Changchun, Harbin and Jiamusi) from June 28 to July 8, 2023 by local centers for disease control and prevention and MSM communities. The sample size was estimated to be 220. Information about their demographics, monkeypox-related knowledge awareness, perceived concern about epidemic risk perception, and monkeypox vaccination intention were collected. Logistic regression model was used to analyze related factors for MSM's monkeypox vaccination intention. Results: In 355 MSM, 63.9% (227/355) had monkeypox vaccination intentions, and 55.5% (197/355) had high awareness of monkeypox related knowledge with a mean knowledge awareness score of 3.7±1.5. MSM with education level of high-school and above (aOR=1.93, 95%CI:1.01-3.69), higher knowledge awareness score (aOR=1.19, 95%CI:1.02-1.40) and higher risk perception of monkeypox infection (aOR=1.82, 95%CI:1.15-2.88), were more willing to receive monkeypox vaccination. The main reasons for willingness to receive monkeypox vaccine were preventing monkeypox (86.3%, 196/227) and worrying about appearance being affected (62.1%, 141/227). The main reasons for unwillingness for the vaccination included concerns about vaccine safety (53.1%, 68/128), clinical progression of AIDS being affected (46.1%, 59/128) and efficacy of antiretroviral therapy being affected (44.5%, 57/128). Conclusions: The levels of knowledge awareness and vaccine intentions still need to be improved among MSM in five cities of northeast China. It is necessary to improve the awareness of monkeypox and intention of monkeypox vaccination, promote protected sex behavior and self-assessment of infection risk, reduce vaccine hesitancy and increase monkeypox vaccination intention in MSM in 5 cities in northeast China.

Prospective monitoring of adverse events following vaccination with Modified vaccinia Ankara - Bavarian Nordic (MVA-BN) administered to a Canadian population at risk of Mpox: A Canadian Immunization Research Network study.

MVA-BN is an orthopoxvirus vaccine that provides protection against both smallpox and mpox. In June 2022, Canada launched a publicly-funded vaccination campaign to offer MVA-BN to at-risk populations including men who have sex with men (MSM) and sex workers. The safety of MVA-BN has not been assessed in this context. To address this, the Canadian National Vaccine Safety Network (CANVAS) conducted prospective safety surveillance during public health vaccination campaigns in Toronto, Ontario and in Vancouver, British Columbia. Vaccinated participants received a survey 7 and 30 days after each MVA-BN dose to elicit adverse health events. Unvaccinated individuals from a concurrent vaccine safety project evaluating COVID-19 vaccine safety were used as controls. Vaccinated and unvaccinated participants that reported a medically attended visit on their 7-day survey were interviewed. Vaccinated participants and unvaccinated controls were matched 1:1 based on age group, gender, sex and provincial study site. Overall, 1,173 vaccinated participants completed a 7-day survey, of whom 75 % (n = 878) also completed a 30-day survey. Mild to moderate injection site pain was reported by 60 % of vaccinated participants. Among vaccinated participants 8.4 % were HIV positive and when compared to HIV negative vaccinated individuals, local injection sites were less frequent in those with HIV (48 % vs 61 %, p = 0.021), but health events preventing work/school or requiring medical assessment were more frequent (7.1 % vs 3.1 %, p = 0.040). Health events interfering with work/school, or requiring medical assessment were less common in the vaccinated group than controls (3.3 % vs. 7.1 %, p < 0.010). No participants were hospitalized within 7 or 30 days of vaccination. No cases of severe neurological disease, skin disease, or myocarditis were identified. Our results demonstrate that the MVA-BN vaccine appears safe when used for mpox prevention, with a low frequency of severe adverse events and no hospitalizations observed.

Perception and Awareness about Monkeypox and Vaccination Acceptance in an At-Risk Population in Brescia, Italy: An Investigative Survey.

Before 2022, monkeypox virus (Mpox) infection in humans was seldom reported outside Africa. During the May 2022 outbreak, most cases were detected among men who have sex with men (MSM). Since Mpox is largely unknown to the general population, through a self-completion questionnaire, we investigated the behaviours and knowledge of our at-risk population belonging to the sexually transmitted infection (STI) outpatient clinic of the Infectious Diseases Unit of the ASST Spedali Civili of Brescia, Italy, between August and October 2022. Most patients that took part in the compilation are HIV positive MSM. The other participants were HIV-seronegative patients with other STIs. Overall, 144 questionnaires were compiled. Most of the participants were Italians (130;90%) and males (139;96.5%) between 30 and 60 years (118;82%). Almost all (136;94%) reported having heard about Mpox and more than half (80;56%) received information about the transmission. Twenty-four respondents (16%) received information from health professionals and 14 (10%) believed that the information received was complete. Although 41% of respondents thought they were at risk of getting the infection and 62% were afraid to get it, the majority (56%) did not increase the precautions taken. When asked if they would accept a vaccine to prevent the disease, more than a third (32%) of respondents expressed hesitation or complete refusal to be vaccinated. Based on our results, what emerges is that there is still a lack of knowledge and awareness about Mpox. To address this issue, targeted health promotion and education strategies that provide the necessary resources to reduce risk behaviours and enhance connections with healthcare professionals are needed.

[Monkeypox: characteristics in female population, Buenos Aires, Argentina]. / Viruela símica: características en población femenina, Buenos Aires, Argentina.

Monkeypox is a zoonotic viral disease caused by a virus of the genus Orthopoxvirus. As of January 1, 2022, it has been reported in 110 WHO Member States. It presents with fever, fatigue, painful lymphadenopathy, and rash. It lasts between 2 and 4 weeks. It is usually self-limited, but severe cases have been described in immunocompromised people. This study describes cases of monkeypox in women, diagnosed between June 2022 and February 2023, and it reports epidemiology, clinical aspects, and complications after infection. A retrospective observational study was carried out in the Febrile Emergency Unit (UFU), reviewing positive cases (RT-PCR) for monkeypox and the population with female biological sex was selected. They were questioned about gynecological complications, menstrual pattern, dyspareunia and pelvic pain. 340 consultations for monkeypox were made, 214 (63%) were positive, 211 cases (99%) male and 3 cases (1%) female. Among these cases is a trans woman, who was not included. The average age is 31 years, immunocompetent, with a negative serology report for HIV, syphilis, hepatitis B and C. Both cases had sexual intercourse without a barrier method. The most frequent symptoms are asthenia and skin lesions, especially in the upper and lower limbs, perianal and genital region. As a risk factor they presented unprotected sexual contact. Within the differential diagnoses, other sexually transmitted infections (STIs) should be considered. There were no gynecological complications reported during follow-up.

La viruela símica es una enfermedad viral zoonótica debida a un virus del género Orthopoxvirus. Desde el 1 de enero de 2022, se ha notificado en 110 Estados Miembros de la OMS. Se presenta con fiebre, astenia, linfoadenopatías dolorosas y exantema. Dura entre 2 y 4 semanas. Suele ser autolimitada y se han descrito casos graves en personas inmunocomprometidas. El presente trabajo describe casos de viruela símica en mujeres, diagnosticados entre junio del 2022 y febrero del 2023 Se realizó un estudio observacional retrospectivo en la Unidad Febril de Urgencias (UFU), revisando casos positivos (RT-PCR) para viruela símica y se seleccionó la población con sexo biológico femenino. Se consultó sobre complicaciones ginecológicas, patrón menstrual, dispareunia y dolor pélvico. Se realizaron 340 consultas por viruela símica, 214 (63%) fueron positivos, 211 casos (99%) de sexo masculino y 3 casos (1%) femeninos. Dentro de estos casos se encuentra una mujer trans, la cual no se incluyó. La edad promedio es de 31 años, inmunocompetentes, con reporte de serologías negativas para HIV, sífilis, hepatitis B y C. Ambos casos mantuvieron relaciones sexuales sin método de barrera. Los síntomas más frecuentes fueron astenia y lesiones en piel, sobre todo en miembros superiores e inferiores, región perianal y genital. Como factor de riesgo presentaron contacto sexual sin protección. Dentro de los diagnósticos diferenciales, debe tenerse en cuenta otras infecciones de transmisión sexual (ITS). En seguimiento epidemiológico no refirieron complicaciones ginecológicas.

First case of MPox in Pakistan: What can we learn from it?

Background and Aims: This research paper discusses Pakistan's healthcare systems' challenges in managing the monkeypox outbreak in Pakistan. Monkeypox is a zoonotic viral disease caused by the monkeypox virus. The World Health Organization declared it a global public health emergency due to the surge in cases worldwide. Pakistan reported its first verified case in April 2023, necessitating immediate response. Body: This correspondence emphasizes on early detection, rapid diagnostic testing, and prompt treatment to limit the virus's transmission. Prevention strategies such as vaccination and travel restrictions on suspected cases are crucial for containment. Lessons from controlling the coronavirus disease 2019 pandemic can inform strategies for monkeypox. Conclusion: The recent outbreak of monkeypox has presented challenges to healthcare systems. Therefore, a coordinated approach involving healthcare providers, government organizations, and the public is crucial in controlling the monkeypox outbreak. Further research is necessary to understand the virus and develop effective interventions for future outbreaks.

Analysis of tweets discussing the risk of Mpox among children and young people in school (May-October 2022): a retrospective observational study.

OBJECTIVE: To determine the number of tweets discussing the risk of Mpox to children and young people in school and (1) determine accuracy, (2) for inaccurate tweets, determine if risk was minimised or exaggerated and (3) describe the characteristics of the accounts and tweets which contained accurate versus inaccurate information. DESIGN: Retrospective observational study. SETTING: Twitter advanced search in January 2023 of tweets spanning 18 May 2022-19 September 2022. PARTICIPANTS: Accounts labelled as: MD, DO, nurse, pharmacist, physical therapist, other healthcare provider, PhD, MPH, Ed. degree, JD, health/medicine/public policy reporter (including students or candidates) who tweeted about the risk of Mpox to children and young people in school. EXPOSURES: Tweets containing the keywords 'school' and 'mpox', 'pox', or 'monkeypox' from May to October 2022. MEASURES: (1) The total and ratio of accurate versus inaccurate tweets, the latter further subdivided by exaggerating or minimising risk, and stratified by account author credential type. (2) The total likes, retweets and follower counts by accurate versus inaccurate tweets, by month and account credentials. (3) Twitter user exposure to inaccurate versus accurate tweets was estimated. RESULTS: 262 tweets were identified. 215/262 (82%) were inaccurate and 215/215 (100%) of these exaggerated risks. 47/262 (18%) tweets were accurate. There were 163 (87%) unique authors of inaccurate tweets and 25 (13%) of accurate tweets. Among healthcare professionals, 86% (95/111) of tweets were inaccurate. Multiplying accuracy by followers and retweets, Twitter users were approximately 974× more likely to encounter inaccurate than accurate information. CONCLUSION: Credentialed Twitter users were 4.6 times more likely to tweet inaccurate than accurate messages. We also demonstrated how incorrect tweets can be quickly amplified by retweets and popular accounts. In the case of Mpox in children and young people, incorrect information always exaggerated risks.

Prospective screening for monkeypox infection among users of HIV pre-exposure prophylaxis in Denmark.

INTRODUCTION: During the 2022 outbreak of mpox (previously called monkeypox), which primarily affected Gay, Bisexual, and other Men who have Sex with Men (GBMSM), testing was mainly limited to individuals with symptoms of infection. Although sporadic cases of mpox continue to be diagnosed in Denmark, the feasibility of screening asymptomatic high-risk populations, such as those using HIV pre-exposure prophylaxis (PrEP), is still unknown. METHODS: During the autumn of 2022, a rectal swab test for mpox PCR was included in the routine sexually transmitted infections (STI) screening for PrEP users. RESULTS: The screening included 224 asymptomatic men with a median age of 36.5 years. One patient (0.4%) tested positive for mpox. Ten (4.5%) and nine (4.0%) had chlamydia and gonorrhea, respectively. DISCUSSION: Our study demonstrates that screening for mpox is feasible in two Danish PrEP clinics.

Clinical Features of Mpox Patients in Korea: A Multicenter Retrospective Study.

BACKGROUND: Mpox is a viral illness with a characteristic skin rash caused by the monkeypox virus. In 2022, Mpox spread throughout the world, and an epidemic through domestic transmission started in South Korea in early 2023. This study aimed to summarize the clinical features of Mpox patients in South Korea. METHODS: This is a multicenter retrospective study conducted at four hospitals in South Korea. All adult patients diagnosed with Mpox who were admitted to the study hospitals between June 1, 2022 and May 26, 2023 and were discharged by June 30, 2023 were reviewed. RESULTS: Sixty patients were included, accounting for 65.9% of Mpox cases reported in South Korea during the study period. Median age was 32 years and 97% (58/60) of patients were male. In total, 85% (51/60) of patients reported their sexual orientation as homosexual or bisexual. The most common route of transmission was sexual or close contact (55/60). Every patient had a skin rash and 88% (53/60) had constitutional symptoms. In total, 42% (25/60) of patients had human immunodeficiency virus and 25% (15/60) had concomitant sexually transmitted infections. Severe manifestations of Mpox were identified in only two patients. CONCLUSION: Mpox patients in South Korea were mainly young adult males and were infected through sexual contact. The clinical outcomes were favorable.

Immunogenicity and reactogenicity of modified vaccinia Ankara pre-exposure vaccination against mpox according to previous smallpox vaccine exposure and HIV infection: prospective cohort study.

Background: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve quickly adequate coverage in front of low supplies. Using epidemiological models, real-life effectiveness was estimated at approximately 36%-86%, but no clinical trials were performed. Few data on MVA-BN immunogenicity are currently available, and there are no established correlates of protection. Immunological response in PLWH in the context of the 2022 outbreak was also poorly described. Methods: Blood samples were collected from participants eligible for pre-exposure MVA-BN vaccination before (T1) receiving a full course of vaccine (single-dose for vaccine-experienced or smallpox-primed and two-dose for smallpox vaccine-naïve or smallpox non-primed) and one month after the last dose (T2 and T3, respectively). MPXV-specific IgGs were measured by in-house immunofluorescence assay, using 1:20 as screening dilution, MPXV-specific nAbs by 50% plaque reduction neutralization test (PRNT50, starting dilution 1:10), and IFN-γ-producing specific T cells to MVA-BN vaccine, by ELISpot assay. Paired or unpaired t-test and Wilcoxon or Mann-Whitney test were used to analyse IgG and nAbs, and T-cell response, as appropriate. The probability of IgG and nAb response in vaccine-experienced vs. vaccine-naïve was estimated in participants not reactive at T1. The McNemar test was used to evaluate vaccination's effect on humoral response both overall and by smallpox vaccination history. In participants who were not reactive at T1, the proportion of becoming responders one month after full-cycle completion by exposure groups was compared by logistic regression and then analysed by HIV status strata (interaction test). The response was also examined in continuous, and the Average Treatment Effect (ATE) of the difference from baseline to schedule completion according to previous smallpox vaccination was estimated after weighting for HIV using a linear regression model. Self-reports of adverse effects following immunization (AEFIs) were prospectively collected after the first MVA-BN dose (T1). Systemic (S-AEFIs: fatigue, myalgia, headache, GI effects, chills) and local (L-AEFIs: redness, swelling, pain) AEFIs were graded as absent (grade 0), mild (1), moderate (2), or severe (3). The maximum level of severity for S-AEFIs and L-AEFIs ever experienced over the 30 days post-dose by vaccination exposure groups were analysed using a univariable multinomial logistic regression model and after adjusting for HIV status; for each of the symptoms, we also compared the mean duration by exposure group using an unpaired t-test. Findings: Among the 164 participants included, 90 (54.8%) were smallpox vaccine-experienced. Median age was 49 years (IQR 41-55). Among the 76 (46%) PLWH, 76% had a CD4 count >500 cells/µL. There was evidence that both the IgG and nAbs titers increased after administration of the MVA-BN vaccine. However, there was no evidence for a difference in the potential mean change in humoral response from baseline to the completion of a full cycle when comparing primed vs. non-primed participants. Similarly, there was no evidence for a difference in the seroconversion rate after full cycle vaccination in the subset of participants not reactive for nAbs at T1 (p = 1.00 by Fisher's exact test). In this same analysis and for the nAbs outcome, there was some evidence of negative effect modification by HIV (interaction p-value = 0.17) as primed people living with HIV (PLWH) showed a lower probability of seroconversion vs. non-primed, and the opposite was seen in PLWoH. When evaluating the response in continuous, we observed an increase in T-cell response after MVA-BN vaccination in both primed and non-primed. There was evidence for a larger increase when using the 2-dose vs. one-dose strategy with a mean difference of -2.01 log2 (p ≤ 0.0001), after controlling for HIV. No evidence for a difference in the risk of developing any AEFIs of any grade were observed by exposure group, except for the lower risk of grade 2 (moderate) fatigue, induration and local pain which was lower in primed vs. non-primed [OR 0.26 (0.08-0.92), p = 0.037; OR 0.30 (0.10-0.88), p = 0.029 and OR 0.19 (0.05-0.73), p = 0.015, respectively]. No evidence for a difference in symptom duration was also detected between the groups. Interpretation: The evaluation of the humoral and cellular response one month after the completion of the vaccination cycle suggested that MVA-BN is immunogenic and that the administration of a two-dose schedule is preferable regardless of the previous smallpox vaccination history, especially in PLWH, to maximize nAbs response. MVA-BN was safe as well tolerated, with grade 2 reactogenicity higher after the first administration in vaccine-naïve than in vaccine-experienced individuals, but with no evidence for a difference in the duration of these adverse effects. Further studies are needed to evaluate the long-term duration of immunity and to establish specific correlates of protection. Funding: The study was supported by the National Institute for Infectious Disease Lazzaro Spallanzani IRCCS "Advanced grant 5 × 1000, 2021" and by the Italian Ministry of Health "Ricerca Corrente Linea 2".

Impact of vaccination and high-risk group awareness on the mpox epidemic in the United States, 2022-2023: a modelling study.

Background: The unprecedented global outbreak of mpox in 2022 posed a public health challenge. In addition to the mpox vaccine campaign in the United States (US), community organisations and public health agencies initiated educational efforts to promote sexual risk reduction. This modelling study estimated the impact of the two-dose vaccination campaign and sexual behaviour changes coincident with high-risk group awareness on the mpox epidemic in the US. Methods: We fitted a deterministic, risk-structured SEIARV model to the epidemic curve of reported mpox cases in the US between May 22, 2022 and December 22, 2022. We evaluated the putative effects of the two preventive responses in the US -- vaccination and sexual risk reduction -- at the population-level, by calculating the prevention percentages of cumulative cases compared to the counterfactual scenario without interventions. We performed sensitivity analyses with four parameters: case reporting fidelity, vaccine effectiveness, proportion of asymptomatic cases, and assortative mixing. Findings: Model fitting revealed a basic reproduction number of 3.88 and 0.39 for the high-risk and low-risk populations, respectively, with 71.8% of mpox cases estimated from the high-risk population. A two-dose vaccination campaign, solely, could prevent 21.2% (10.2%-24.1%) of cases, while behaviour changes due to high-risk group awareness alone could prevent 15.4% (14.3%-20.6%). The combination of both measures were synergistic, with the model suggesting that 64.0% (43.8%-69.0%) of US cases were averted that would have otherwise occurred. Interpretation: Our models suggest that the 2022-2023 mpox epidemic in the US was controlled by a combination of two-dose mpox vaccination campaign and high-risk group awareness and sexual risk reduction. Funding: Taiwan Ministry of Education grant #NTU-112L9004, Taiwan National Science and Technology Council grant #MOST-109-2314-B-002-147-MY3 and grant #NSC-112-2314-B-002-216-MY3. SHV was supported, in part, by US National Institutes of Health grant #P30MH062294.

Fabrication of label-free immunoprobe for monkeypox A29 detection using one-step electrodeposited molybdenum oxide-graphene quantum rods.

Monkeypox is a zoonotic viral infection caused by the monkeypox virus (MPXV), which belongs to the Poxviridae family of the Orthopoxvirus (OPXV) genus. Monkeypox is transmitted from animals to humans and humans to humans; therefore, the accurate and early detection of MPXV is crucial for reducing mortality. A novel graphene-based material, graphene quantum rods (GQRs) was synthesized and confirmed using high-resolution transmission electron microscopy (HR-TEM) and atomic force microscopy (AFM). In this study, molybdenum oxide was electrodeposited and one-pot electrodeposition of MoO3-GQRs composite on carbon fiber paper (CFP) enabled by an antibody (Ab A29)/MoO3-GQRs immunoprobe was developed for the early diagnosis of MPXV protein (A29P). Several studies were conducted to analyze the MoO3-GQRs composite, and the prepared Ab A29/MoO3-GQRs immunoprobe selectively bound to the A29P antigen that was measured using differential pulse voltammetry (DPV) analysis and impedance spectroscopy. The antigen-antibody interaction was analyzed using X-ray photoelectron spectroscopy. DPV analysis showed a wide linear range of detection from 0.5 nM to 1000 nM, a detection limit of 0.52 nM, and a sensitivity of 4.51 µA in PBS. The prepared immunoprobe was used to analyze A29P in serum samples without reducing electrode sensitivity. This system is promising for the clinical analysis of A29P antigen and offers several advantages, including cost-effectiveness, ease of use, accuracy, and high sensitivity.