The wet nurses of the Hospital Real of Santiago de Compostela between 1803 and 1808.

Objective: To analyze the duties of wet nurses at the Hospital Real in Santiago de Compostela (Spain). The secondary objectives were to compare the mortality rate and distribution by parish of the foundlings under the care of the Royal House between 1803 and 1808; and to determine the origin of the Galician foundlings who participated in the Royal Philanthropic Expedition of the Smallpox Vaccine in 1803. Methods: Historiographic study that analyzed sorted and not sorted in series indirect positional and quantitative historical sources. Results: The duties of wet nurses during the studied period were to provide basic care and cultural instruction. The mortality rate of foundlings fluctuated during that period and their distribution by parish (functional unit of healthcare services at that time) was similar in those years, with a predominance in the provinces of A Coruña and Pontevedra. A total of 5 Galician foundlings from the House analyzed were part of the smallpox vaccine expedition, their names were Juan Antonio, Jacinto, Gerónimo María, Francisco Florencio and Juan Francisco. Conclusion: During the observed period the wet nurses of the Hospital Real of Santiago de Compostela were in charge of pediatric care. Wet nurses were vital in the role of keeping the foundlings alive and can be considered as one of the forerunners of the pediatric nurse profession at that time.

Mpox-specific immune responses elicited by vaccination or infection in people living with HIV.

In the recent mpox outbreak, people living with HIV (PLWH) were at high risk both for contracting infection and for suffering a more severe disease course. We studied cellular and humoral immune responses elicited by mpox infection (n = 5; n = 3 PLWH) or smallpox vaccination (n = 17; all PLWH) in a cohort of men who have sex with men. All PLWH were successfully treated, with stable CD4 counts and undetectable HIV viral loads. 11/17 vaccinated individuals had received childhood smallpox vaccination. In this group of individuals, both two-dose MVA-vaccination and natural infection evoked mpox-specific immune responses mediated by B cells as well as CD4 and CD8 T cells. This study improves our understanding of smallpox vaccination mediated cross-reactivity to other orthopox viruses, and the long-lasting durability of childhood smallpox vaccination mediated immune responses including in PLWH.

The Current State and Progress of Mpox Vaccine Research.

On July 23, 2022, the World Health Organization (WHO) declared the monkeypox (mpox) outbreak a "Public Health Emergency of International Concern." Since 2022, outbreaks of mpox in many countries around the world have primarily resulted in fatalities among immunocompromised individuals, such as untreated HIV/AIDS patients. Since the eradication of smallpox was declared by the WHO in 1980, the global vaccination against smallpox has been gradually discontinued. China also stopped routine smallpox vaccination in 1981. The protective effect of the smallpox vaccine has decreased over time due to aging and declining immunity in those who were vaccinated. For individuals, timely vaccination against smallpox is an effective means of protection against mpox. However, due to safety concerns with the smallpox vaccine and the limitations of current mpox vaccines, there is no vaccine that is safe, effective, and has low side effects applied in clinical settings. This article provides a comprehensive review of the development of mpox virus (MPXV) vaccines, their application in special populations, and the current state of vaccine research, considering the etiology, transmission, and prevention of the MPXV. Vaccination, as an effective method of epidemic prevention, can provide long-term immune protection and effectively reduce the severity of infection. However, as there is no licensed specific MPXV vaccine available globally, the vaccines currently used for mpox prevention are mostly smallpox vaccines. These smallpox vaccines can offer some degree of protection against mpox by activating cross-protection in the body.

The association between BCG scars and self-reported chronic diseases: A cross-sectional observational study within an RCT of Danish health care workers.

INTRODUCTION: The live-attenuated vaccines Bacillus Calmette-Guérin (BCG) and Vaccinia have been associated with beneficial non-specific effects. We assessed the prevalence of BCG and Vaccinia vaccine scars in a cohort of Danish health care workers and investigated the association between the presence of vaccine scars and self-reported chronic diseases. METHODS: Cross-sectional study utilizing baseline data collected during 2020-2021 at enrollment in a BCG trial aiming to assess the effect of BCG vaccination on absenteeism and infectious disease morbidity during the SARS-COV-2 pandemic. In Denmark, Vaccinia was discontinued in 1977, and BCG was phased out in the early 1980s. We used logistic regression analysis (adjusted for sex, birth year, and smoking status) to estimate the association between scar status and chronic diseases, providing adjusted Odds Ratios (aORs) with 95 % Confidence Intervals, for participants born before 1977, and born from 1965 to 1976. RESULTS: The cohort consisted of 1218 participants (206 males; 1012 females) with a median age of 47 years (Q1-Q3: 36-56). Among participants born 1965-1976 (n = 403), who experienced the phase-outs, having BCG and/or Vaccinia scar(s) vs. having no vaccine scars yielded an aOR of 0.51 (0.29-0.90) of self-reported chronic disease; an effect primarily driven by BCG. In the same birth cohort, having vaccine scar(s) was most strongly associated with a lower prevalence of chronic respiratory and allergic diseases; the aORs being 0.39 (0.16-0.97) and 0.39 (0.16-0.91), respectively. CONCLUSION: Having a BCG scar was associated with a lower prevalence of self-reported chronic disease.

Live attenuated smallpox vaccine candidate (KVAC103) efficiently induces protective immune responses in mice.

Smallpox, caused by the variola virus belonging to the genus Orthopoxvirus, is an acute contagious disease that killed 300 million people in the 20th century. Since it was declared to be eradicated and the national immunization program against it was stopped, the variola virus has become a prospective bio-weapon. It is necessary to develop a safe vaccine that protects people from terrorism using this biological weapon and that can be administered to immunocompromised people. Our previous study reported on the development of an attenuated smallpox vaccine (KVAC103). This study evaluated cellular and humoral immune responses to various doses, frequencies, and routes of administration of the KVAC103 strain, compared to CJ-50300 vaccine, and its protective ability against the wild-type vaccinia virus Western Reserve (VACV-WR) strain was evaluated. The binding and neutralizing-antibody titers increased in a concentration-dependent manner in the second inoculation, which increased the neutralizing-antibody titer compared to those after the single injection. In contrast, the T-cell immune response (interferon-gamma positive cells) increased after the second inoculation compared to that of CJ-50300 after the first inoculation. Neutralizing-antibody titers and antigen-specific IgG levels were comparable in all groups administered KVAC103 intramuscularly, subcutaneously, and intradermally. In a protective immunity test using the VACV-WR strain, all mice vaccinated with CJ-50300 or KVAC103 showed 100% survival. KVAC103 could be a potent smallpox vaccine that efficiently induces humoral and cellular immune responses to protect mice against the VACV-WR strain.

What determines mpox vaccination uptake? Assessing the effect of intent-to-vaccinate versus other determinants among men who have sex with men.

BACKGROUND: In response to the mpox outbreak, vaccination was offered in the Netherlands to men who have sex with men (MSM) at increased risk for mpox. Successful vaccination campaigns are leveraged by high intent-to-vaccinate, yet intent might not always lead to uptake. Therefore, we assessed the impact of intent-to-vaccinate and other factors on vaccination uptake among participants of the Amsterdam Cohort Studies (ACS). METHOD: In July 2022, prior to the mpox vaccination campaign, we distributed an online survey regarding mpox intent-to-vaccinate, as well as e.g. beliefs, attitude, subjective norms, and perception of risk among ACS participants (all MSM). Vaccination uptake was self-reported during study visits after August 2022. The association between vaccination intent and uptake, and determinants of intent, was jointly assessed using a structural equation model (SEM) based on components of the Theory of Planned Behavior (TPB). In a second SEM, determinants of intent were allowed to have a direct effect on vaccination uptake. RESULTS: 492 MSM (median age = 46 years) were included in analyses. 380 (77%) had high intent-to-vaccinate and 238 (48%) received at least one vaccine dose. In the first model with a direct relation between intent and uptake only, TBP components predicted intent as expected, and high intent-to-vaccinate was significantly associated with getting vaccinated (ß = 1.1, 95%CI = 0.6-1.5). However, 175/380 (46%) participants with high intent-to-vaccinate did not get vaccinated. The second model had an improved model fit compared to the first model. The effect of intent on uptake was non-significant, and only perceiving to be at higher risk of infection significantly increased vaccination uptake later on (ß = 0.42, 95%CI = 0.26-0.59). Having a steady relationship decreased the probability of vaccination (ß = -0.59, 95%CI = -1.0- -0.18). CONCLUSIONS: While intent-to-vaccinate for mpox was high among MSM, high intent did not necessarily result in vaccine uptake. Mpox risk perception might have played a more pivotal role in getting vaccinated, which may be related to the evolution of vaccination eligibility criteria and accessibility to the vaccine.

Evaluation of Cross-Immunity to the Mpox Virus Due to Historic Smallpox Vaccination.

When the Mpox virus (MPXV) began spreading globally in 2022, it became critical to evaluate whether residual immunity from smallpox vaccination provided cross-protection. To assess the cross-immune response to MPXV, we collected serum samples (n = 97) and PBMCs (n = 30) from healthy-donors, either born before 1974 and reporting smallpox vaccination during childhood or born after 1975 and not vaccinated with Vaccinia virus (VACV)-based vaccines. We evaluated the levels of anti-MPXV IgG and neutralizing antibodies (Nabs) and the presence of a T cell response against MPXV. We found anti-MPXV IgG and Nabs in 60 (89.6%) and 40 (70.1%) vaccinated individuals, respectively. We observed a T cell response to Orthopoxviruses and MPXV peptide pools in 30% of vaccinated individuals. We thus show that a high proportion of subjects who received the smallpox vaccine 40 to 60 years ago have humoral cross-immunity, while the T-cell-specific response against MPXV was observed in a smaller group (30%) of vaccinated individuals. This study, combined with information on immunity developed during natural infection or the administration of current vaccines, will contribute to a better understanding of humoral and cellular responses against MPXV.

Acceptance and timeliness of post-exposure vaccination against mpox in high-risk contacts, Amsterdam, the Netherlands, May-July 2022.

BACKGROUND: May 2022, several countries reported mpox outbreaks among men-who-have-sex-with-men. In the Netherlands, high-risk contacts were offered the third-generation smallpox vaccine as post-exposure-prophylaxis (PEP) within 4 but maximum 14 days after exposure. We investigated their PEP acceptance, timeliness of uptake and development of mpox for the region of the Public Health Service (PHS) Amsterdam. METHODS: High-risk contacts identified during 20 May-22 July 2022 were included. Contacts were followed-up 21 days after exposure and classified as: no patient (no mpox symptoms or orthopoxvirus PCR-negative) or mpox patient (clinically suspected mpox or orthopoxvirus PCR-positive). We calculated time intervals between date of last exposure and first PHS consultation, PEP administration, and symptom onset. RESULTS: Two-hundred-ninety contacts were at high-risk of mpox predominantly due to sexual and/or direct skin-skin contact (212/290, 73 %). First PHS consultation was a median of 5 (IQR 3, 7) days after exposure, at which point 26/290 (9 %) contacts were ineligible for PEP. 84 % (223/264) of contacts eligible for PEP, received PEP within a median of 6 (IQR 3, 8) days after exposure. Of 282 contacts (missing outcome n = 8) 38 (14 %) developed mpox a median of 7 (IQR 5, 12) days after exposure, of whom 50 % (19/38) developed mpox before their first PHS consultation. Among contacts eligible for PEP, 2/38 (5 %) unvaccinated and 16/218 (7 %) vaccinated contact developed mpox. CONCLUSIONS: PEP acceptance among contacts of mpox patients was high. However, PEP timeliness was inadequate. Half of contacts received PEP 6 or more days after exposure, and half of contacts who developed mpox had an onset prior to their first PHS consultation. Estimating PEP vaccine effectiveness is problematic due to the timeliness of PEP and the time it takes to generate vaccine-induced immunity. It is important to assess how PEP timeliness may improve and to promote pre-exposure vaccination to control mpox outbreaks.

Manejo desde atención primaria de la infección por la viruela del mono (MPOX) en humanos / Management from Primary Care of monkeypox infection (MPOX) in humans

La viruela del mono (MPOX) es una zoonosis vírica endémica en países de África occidental o central que esporádicamente se exporta a otras regiones. En mayo del 2022, comenzó a ocurrir un brote mundial de viruela MPOX en varias naciones de Europa y Norteamérica. La mayoría de los casos notificados se identificaron a nivel ambulatorio y afectaron principalmente a hombres que tienen sexo con hombres (HSH). El contagio es por contacto estrecho con lesiones, líquidos corporales, secreciones respiratorias o con material contaminado, de persona o animal infectado. El cuadro clínico es similar a la viruela humana, con menor gravedad. Predomina la afectación cutánea leve y autolimitada tras dos a cuatro semanas. En HSH aparecen lesiones cutáneas atípicas debido a la manera de contagio. En ciertos grupos de riesgo pueden presentarse formas graves o complicaciones. La tasa de letalidad es de 3 a 6% según el clado responsable. El diagnóstico de sospecha se confirma con la detección del virus, a partir de exudados de las lesiones o costras, con técnicas de amplificación de ácidos nucleicos mediante reacción en cadena de la polimerasa (PCR) convencional o en tiempo real. El manejo clínico en la mayoría de los casos se realiza desde atención primaria (AP), mediante el control de los principales síntomas. Entre 5 a 10% requieren un manejo hospitalario y existen algunas opciones de tratamiento antiviral específico. Las vacunas frente a la viruela humana protegen contra la MPOX y se utilizan como profilaxis pre y posexposición a personas de riesgo. Las medidas para reducir la exposición al virus, es la principal estrategia de prevención de la MPOX. Además, el papel del médico de familia es clave para controlar la propagación del virus de la MPOX mediante la vigilancia activa y el diagnóstico temprano de la enfermedad.(AU)

Monkeypox (MPOX) is a viral zoonosis endemic in West or Central African countries that is sporadically exported to another area. In May 2022, a global outbreak of MPOX smallpox began to occur in several countries in Europe and North America. Most of the reported cases are identified at the outpatient level and mainly affect men who have sex with men (MSM). Transmission is by close contact with lesions, body fluids, respiratory secretions or contaminated material from an infected person or animal. The clinical picture is similar to human smallpox, with less severity. Mild, self-limiting skin involvement predominates after 2-4 weeks. In MSM, atypical skin lesions appear due to the mode of infection. Severe forms or complications may appear in certain risk groups. The case fatality rate is 3%-6% depending on the clade responsible. The diagnosis of suspicion is confirmed by detection of the virus from exudates of lesions or scabs, with nucleic acid amplification techniques by conventional or real-time PCR. Clinical management in most cases is performed in primary care (PC), by monitoring the main symptoms. Between 5-10% require hospital management and there are some specific antiviral treatment options. Human smallpox vaccines protect against MPOX and are used as pre- and post-exposure prophylaxis for persons at risk. Measures to reduce exposure to the virus are the main MPOX prevention strategy. In addition, the role of the family physician is key to controlling the spread of MPOX through active surveillance and early diagnosis of the disease.(AU)

Proctitis y úlcera ano-rectal como presentación inicial en pacientes con Viruela símica

Objetivo: Describir hallazgos clínicos, quirúrgicos e imagenológicos de la patología anorrectal en pacientes con Viruela Símica. Materiales y Métodos: Reporte de serie de casos clínicos, observacional, en pacientes con Viruela Símica tratados en un centro de salud privado desde agosto 2022 a diciembre 2022. Resultados: El 100% de los casos pertenecía al sexo masculino, la edad promedio fue de 32 años, todos los pacientes mantuvieron relaciones sexuales con otros hombres, la mayoría debuto con síntomas rectales, incluyendo proctalgia, prurito anal y heces diarreicas con mucosidad. El diagnóstico se confirmó mediante PCR (reacción de polimerasa en cadena) y el tratamiento fue sintomático, con mejoría en todos los pacientes en un seguimiento de 10 días. Discusión: La Viruela Símica es una enfermedad viral que se encuentra, principalmente, en regiones remotas de África Central, con brotes esporádicos en países africanos. Está relacionada con el virus de la viruela y se transmite, principalmente, del contacto con animales infectados o fluidos corporales. La enfermedad presenta síntomas similares a la gripe, seguidos del desarrollo de una erupción cutánea que progresa a pústulas y costras. No hay tratamiento específico para la viruela símica, el manejo medico alivia los síntomas. El brote de viruela símica en 2022 presentó características novedosas y atípicas en su forma de presentación. Conclusión: Los síntomas rectales asociados a una historia clínica compatible con viruela símica se deben considerar como diagnóstico diferencial a la proctitis por esta etiología específica y emergente.

Objective: To describe clinical, surgical and imaging findings of anorectal pathology in patients with monkeypox. Materials and Methods: Observational clinical case series report in patients with monkeypox treated in a private health center from August 2022 to December 2022. Results: 100% of the cases were male, the average age was 32 years old, all patients had sexual intercourse with other men, most debuted with rectal symptoms, including proctalgia, anal itching, and diarrheal stools with mucus. Diagnosis was confirmed by PCR (polymerase chain reaction) and treatment was symptomatic, with improvement in all patients at a 10-day follow-up. Discussion: Monkeypox is a viral disease found mainly in remote regions of Central Africa, with sporadic outbreaks in African countries. It is related to the smallpox virus and is transmitted primarily from contact with infected animals or bodily fluids. The disease presents with flu-like symptoms, followed by the development of a skin rash that progresses to pustules and scabs. There is no specific treatment for monkeypox; medical management alleviates the symptoms. The monkeypox outbreak in 2022 presented novel and atypical characteristics in its presentation. Conclusion: Rectal symptoms associated with a clinical history compatible with monkeypox should be considered as a differential diagnosis of proctitis due to this specific and emerging etiology.

Virus-specific and shared gene expression signatures in immune cells after vaccination in response to influenza and vaccinia stimulation.

Background: In the vaccine era, individuals receive multiple vaccines in their lifetime. Host gene expression in response to antigenic stimulation is usually virus-specific; however, identifying shared pathways of host response across a wide spectrum of vaccine pathogens can shed light on the molecular mechanisms/components which can be targeted for the development of broad/universal therapeutics and vaccines. Method: We isolated PBMCs, monocytes, B cells, and CD8+ T cells from the peripheral blood of healthy donors, who received both seasonal influenza vaccine (within <1 year) and smallpox vaccine (within 1 - 4 years). Each of the purified cell populations was stimulated with either influenza virus or vaccinia virus. Differentially expressed genes (DEGs) relative to unstimulated controls were identified for each in vitro viral infection, as well as for both viral infections (shared DEGs). Pathway enrichment analysis was performed to associate identified DEGs with KEGG/biological pathways. Results: We identified 2,906, 3,888, 681, and 446 DEGs in PBMCs, monocytes, B cells, and CD8+ T cells, respectively, in response to influenza stimulation. Meanwhile, 97, 120, 20, and 10 DEGs were identified as gene signatures in PBMCs, monocytes, B cells, and CD8+ T cells, respectively, upon vaccinia stimulation. The majority of DEGs identified in PBMCs were also found in monocytes after either viral stimulation. Of the virus-specific DEGs, 55, 63, and 9 DEGs occurred in common in PBMCs, monocytes, and B cells, respectively, while no DEGs were shared in infected CD8+ T cells after influenza and vaccinia. Gene set enrichment analysis demonstrated that these shared DEGs were over-represented in innate signaling pathways, including cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, Toll-like receptor signaling, RIG-I-like receptor signaling pathways, cytosolic DNA-sensing pathways, and natural killer cell mediated cytotoxicity. Conclusion: Our results provide insights into virus-host interactions in different immune cells, as well as host defense mechanisms against viral stimulation. Our data also highlights the role of monocytes as a major cell population driving gene expression in ex vivo PBMCs in response to viral stimulation. The immune response signaling pathways identified in this study may provide specific targets for the development of novel virus-specific therapeutics and improved vaccines for vaccinia and influenza. Although influenza and vaccinia viruses have been selected in this study as pathogen models, this approach could be applicable to other pathogens.

Belarusian Healthcare Professionals' Views on Monkeypox and Vaccine Hesitancy.

BACKGROUND: Despite the low transmission risk of Monkeypox (mpox) in Belarus, this study is vital as it contributes to our understanding of vaccine hesitancy among healthcare professionals (HCPs). It aims to assess vaccination perceptions and evaluate the willingness to pay for the vaccine among Belarusian HCPs, thereby enhancing pandemic preparedness. METHODS: in October 2022, a cross-sectional survey-based study was conducted among Belarusian HCPs using a self-administered questionnaire (SAQ). Invitations were disseminated via social media platforms using a snowball sampling method. The SAQ encompassed various categories, including sociodemographic details, medical history, sources of mpox information, perceived and factual mpox knowledge, and perceptions of the mpox vaccine according to the health belief model (HBM), mpox vaccine acceptance and willingness to pay (WTP). RESULTS: while a large proportion of respondents had good knowledge of mpox epidemiology and its clinical manifestations, their awareness of available vaccines and treatment options was limited. Consequently, a significant correlation was found between the history of influenza vaccination and mpox-related knowledge. Furthermore, the study showed that just over half of the participants (51.4%) were willing to receive the mpox vaccine if offered for free, safely, and effectively, with their decision largely influenced by perceived benefits (Spearman's rho = 0.451) and cues to action (Spearman's rho = 0.349). However, a considerable degree of hesitancy (30.6%) and resistance (18.1%) towards the mpox vaccine was observed, underscoring the need for targeted interventions to address these issues. CONCLUSIONS: this study highlights a significant knowledge gap among Belarusian HCPs about mpox vaccines and treatments, despite a general awareness of the disease's epidemiology and symptoms, and it underscores the need for targeted interventions to enhance mpox knowledge and vaccine acceptance.

Efficacy and Safety of the Smallpox Vaccine for Postexposure Prophylaxis in Monkeypox: Protocol for an Open-Labeled, Single-Armed Study.

BACKGROUND: In May 2022, a case of monkeypox (currently known as "mpox") with no history of overseas travel was reported in the United Kingdom, followed by reports of infections reported in Europe, the United States, and other countries worldwide. Due to the significant overlap in immune responses among viruses of the genus Orthopoxvirus (including smallpox virus, mpox virus, and vaccinia virus), it is believed that cross-immunity can be achieved by administering the smallpox virus vaccine. In Japan, a smallpox vaccine (LC16m8 strain vaccine) has been approved; however, there was no regulatory approval for the mpox vaccine during the design of this study. Although it is believed that individuals exposed to the mpox virus may receive smallpox vaccination as mpox prophylaxis, the existing evidence is not clear. OBJECTIVE: The primary objective was to evaluate the efficacy of the LC16m8 strain vaccine, approved for smallpox in Japan, for postexposure prophylaxis against mpox when administered to close contacts of individuals with mpox. The secondary objective was to investigate the safety of the vaccine for postexposure prophylaxis against mpox. METHODS: The study aimed to enroll 100 vaccinated participants who had been identified as close contacts of individuals with mpox. Consent was obtained, and the participants are inoculated with the vaccine. Daily recordings of symptoms (body temperature, headache, rash, and side effects) were made until day 21 and then again on day 28. Furthermore, additional evaluations of adverse events were performed by the investigators on days 7, 14, 21, and 28. Considering that the maximum incubation period for mpox is 21 days, the primary end point is the presence or absence of the disease 21 days after close contact. The primary analysis focused on cases within 4 days of intense contact as it has been reported that vaccination within this timeframe can reduce the incidence of the disease. RESULTS: The first trial participant was enrolled on July 28, 2022, and the research period concluded in March 2023. The study results will be published in a peer-reviewed scientific journal. CONCLUSIONS: This study allowed us to investigate the efficacy and safety of the LC16m8 strain vaccine in postexposure prophylaxis against mpox. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs031220137; https://jrct.niph.go.jp/en-latest-detail/jRCTs031220137. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46955.

An open-label, non-randomized study investigating the safety and efficacy of smallpox vaccine, LC16, as post-exposure prophylaxis for mpox.

Mpox is an acute exanthematous disease caused by the monkeypox virus. Since May 2022, it has spread as a community-acquired infection, mainly in Europe and the United States, and urgent measures to prevent this infection were also required in Japan. In this study, we investigated the post-exposure prophylaxis of mpox and safety after inoculating the smallpox vaccine. Participants in close contact with patients with mpox were inoculated with "Freeze-dried cell culture Smallpox Vaccine LC16," within 14 days after close contact. Six cases were registered, and all the participants were inoculated. No mpox symptoms or related complications were observed in the participants for 21 days after the close contact. Adverse events due to inoculation, such as rash, fever, lymphadenopathy, and local reaction at the inoculation site (comprising erythema, swelling, induration, and pain) were observed in the participants; however, all inoculation-related events were non-severe and non-serious, and the participants recovered during the 28-day observation period. The findings of this study suggest that inoculation with LC16 is an effective post-exposure prophylaxis in individuals who had close contact with patients with mpox. Further large-scale studies are warranted to validate these findings.

Inequity in the global distribution of monkeypox vaccines.

Monkeypox (mpox) has been a public health emergency of international concern that emerged in mid-2022 and has spread to 110 countries. The clinical findings of the disease vary according to the seriousness of the cases. Although its case fatality risk has not been high, a significant percentage of patients require hospitalization. In this context, local initiatives were taken to extend the limited supply of vaccines against the disease; however, such measures have not been sufficient to contain the spread of cases and ensure an equitable distribution of health resources. As a result, endemic regions of low-income countries continue to have insufficient access to mpox vaccination. Despite this and considering the global scope of the disease, there is still little discussion in the literature about the difficulties in achieving adequate vaccination coverage rates for the target population of interest. In this article, we briefly discussed general aspects of the disease, including its surveillance, the current global context of challenges for mpox vaccination, and issues on global allocation of health resources as well as proposed related recommendations.

Identification of novel T-cell epitopes on monkeypox virus and development of multi-epitopes vaccine using immunoinformatics approaches.

Monkeypox virus (MPV) is closely related to the smallpox virus, and previous data from Africa suggest that the smallpox vaccine (VARV) is at least 85% effective in preventing MPV. No multi-epitope vaccine has yet been developed to prevent MPV infection. In this work, we used in silico structural biology and advanced immunoinformatic strategies to design a multi-epitope subunit vaccine against MPV infection. The designed vaccine sequence is adjuvanted with CpG-ODN and includes HTL/CTL epitopes for similar proteins between vaccinia virus (VACV) that induced T-cell production in vaccinated volunteers and the first draft sequence of the MPV genome associated with the suspected outbreak in several countries, May 2022. In addition, the specific binding of the modified vaccine and the immune Toll-like receptor 9 (TLR9) was estimated by molecular interaction studies. Strong interaction in the binding groove as well as good docking scores confirmed the stringency of the modified vaccine. The stability of the interaction was confirmed by a classical molecular dynamics simulation and normal mode analysis. Then, the immune simulation also indicated the ability of this vaccine to induce an effective immune response against MPV. Codon optimization and in silico cloning of the vaccine into the pET-28a (+) vector also showed its expression potential in the E. coli K12 system. The promising data obtained from the various in silico studies indicate that this vaccine is effective against MPV. However, additional in vitro and in vivo studies are still needed to confirm its efficacy.Communicated by Ramaswamy H. Sarma.

Post-exposure vaccine effectiveness and contact management in the mpox outbreak, Madrid, Spain, May to August 2022.

BackgroundAppropriate vaccination strategies have been key to controlling the outbreak of mpox outside endemic areas in 2022, yet few studies have provided information on mpox vaccine effectiveness (VE).AimTo assess VE after one dose of a third-generation smallpox vaccine against mpox when given as post-exposure prophylaxis (PEP) within 14 days.MethodsA survival analysis in a prospective cohort of close contacts of laboratory-confirmed mpox cases was conducted from the beginning of the outbreak in the region of Madrid in May 2022. The study included contacts of cases in this region diagnosed between 17 May and 15 August 2022. Follow up was up to 49 days. A multivariate proportional hazard model was used to evaluate VE in the presence of confounding and interaction.ResultsInformation was obtained from 484 close contacts, of which 230 were vaccinated within 14 days of exposure. Of the close contacts, 57 became ill during follow-up, eight vaccinated and 49 unvaccinated. The adjusted effectiveness of the vaccine was 88.8% (95% CI: 76.0-94.7). Among sexual contacts, VE was 93.6% (95% CI: 72.1-98.5) for non-cohabitants and 88.6% (95% CI: 66.1-96.2) for cohabitants.ConclusionPost-exposure prophylaxis of close contacts of mpox cases is an effective measure that can contribute to reducing the number of cases and eventually the symptoms of breakthrough infections. The continued use of PEP together with pre-exposure prophylaxis by vaccination and other population-targeted prevention measures are key factors in controlling an mpox outbreak.

[Management from Primary Care of monkeypox infection (MPOX) in humans]. / Manejo desde atención primaria de la infección por la viruela del mono (MPOX) en humanos.

Monkeypox (MPOX) is a viral zoonosis endemic in West or Central African countries that is sporadically exported to another area. In May 2022, a global outbreak of MPOX smallpox began to occur in several countries in Europe and North America. Most of the reported cases are identified at the outpatient level and mainly affect men who have sex with men (MSM). Transmission is by close contact with lesions, body fluids, respiratory secretions or contaminated material from an infected person or animal. The clinical picture is similar to human smallpox, with less severity. Mild, self-limiting skin involvement predominates after 2-4 weeks. In MSM, atypical skin lesions appear due to the mode of infection. Severe forms or complications may appear in certain risk groups. The case fatality rate is 3%-6% depending on the clade responsible. The diagnosis of suspicion is confirmed by detection of the virus from exudates of lesions or scabs, with nucleic acid amplification techniques by conventional or real-time PCR. Clinical management in most cases is performed in primary care (PC), by monitoring the main symptoms. Between 5-10% require hospital management and there are some specific antiviral treatment options. Human smallpox vaccines protect against MPOX and are used as pre- and post-exposure prophylaxis for persons at risk. Measures to reduce exposure to the virus are the main MPOX prevention strategy. In addition, the role of the family physician is key to controlling the spread of MPOX through active surveillance and early diagnosis of the disease.

Features of Mpox infection: The analysis of the data submitted to the ID-IRI network.

Background: Mpox is a rare zoonotic disease caused by the Mpox virus. On May 21, 2022, WHO announced the emergence of confirmed Mpox cases in countries outside the endemic areas in Central and West Africa. Methods: This multicentre study was performed through the Infectious Diseases International Research Initiative network. Nineteen collaborating centres in 16 countries participated in the study. Consecutive cases with positive Mpoxv-DNA results by the polymerase chain reaction test were included in the study. Results: The mean age of 647 patients included in the study was 34.5.98.6% of cases were males, 95.3% were homosexual-bisexual, and 92.2% had a history of sexual contact. History of smallpox vaccination was present in 3.4% of cases. The median incubation period was 7.0 days. The most common symptoms and signs were rashes in 99.5%, lymphadenopathy in 65.1%, and fever in 54.9%. HIV infection was present in 93.8% of cases, and 17.8% were followed up in the hospital for further treatment. In the two weeks before the rash, prodromal symptoms occurred in 52.8% of cases. The incubation period was 3.5 days shorter in HIV-infected Mpox cases with CD4 count <200/µL, we disclosed the presence of lymphadenopathy, a characteristic finding for Mpox, accompanied the disease to a lesser extent in cases with smallpox vaccination. Conclusions: Mpox disseminates globally, not just in the endemic areas. Knowledge of clinical features, disease transmission kinetics, and rapid and effective implementation of public health measures are paramount, as reflected by our findings in this study.

Viruela símica grave en un paciente con infección por VIH, Ecuador / Severe mpox in a HIV patient, Ecuador. A case report

En mayo de 2022 se reportó un aumento de casos de viruela símica (mpox en inglés) en el mundo, cuyo comportamiento epidemiológico y clínico, particularmente en pacientes con infección por VIH, condujo a la declaración del brote de mpox 2022 como emergencia de salud pública internacional. Se presenta el caso de un paciente con infección por VIH que cursó con mpox grave y fulminante, con placas necróticas en párpado y membrana inflamatoria sobre la superficie ocular; mucosa oral con lesiones blanquecinas y úlceras en lengua; induración de tejidos blandos y lesiones necróticas en los pies. Tras múltiples complicaciones, se convirtió en la primera víctima fatal reportada en Ecuador en 2022. En pacientes con infección por VIH, mpox puede presentarse como un agente oportunista, causando lesiones cutáneas graves, con o sin manifestaciones sistémicas.

In May 2022 several cases of mpox were reported worldwide, whose epidemiological and clinical outcome, particularly in patients seropositive for HIV, led to declaring the 2022 mpox outbreak as a public health emergency. We describe a case of a patient with HIV infection and severe and fulminant mpox, with necrotic plaques on the eyelid and an inflammatory membrane on the ocular surface; oral mucosa with whitish lesions and ulcers on the tongue; soft tissues induration, and necrotic lesions on the feet. After multiple complications, he became the first fatality reported in Ecuador in 2022. In HIV-infected patients mpox can be considered an opportunistic agent, with severe skin lesions with or without systemic manifestations.