OBJECTIVE: The 2022 mpox epidemic reached a peak in Belgium and the rest of Europe in July 2022, after which it unexpectedly subsided. This study investigates epidemiological, behavioral, and immunological factors behind the waning of the epidemic in Belgium.
METHODS: We investigated temporal evolutions in the characteristics and behavior of mpox patients using national surveillance data and data from a prospective registry of mpox patients in the Institute of Tropical Medicine (Antwerp). We studied behavioral changes in the population at risk using a survey among HIV-preexposure prophylaxis (PrEP) users. We determined the seroprevalence of anti-orthopoxvirus antibodies among HIV-PrEP users across four-time points in 2022.
RESULTS: Mpox patients diagnosed at the end of the epidemic had less sexual risk behavior compared to those diagnosed earlier: they engaged less in sex at mass events, had fewer sexual partners, and were less likely to belong to the sexual network\'s central group. Among HIV-PrEP users there were no notable changes in sexual behavior. Anti-orthopoxvirus seroprevalence did not notably increase before the start of national vaccination campaigns.
CONCLUSIONS: The observed changes in group immunity and behavior in the population at greater risk of exposure to mpox seem unable to explain the waning of the mpox epidemic. A change in the profile of mpox patients might have contributed to the decline in cases.

Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce cross-reactive antibodies against the monkeypox virus (MPXV) and reduce the risk of infection. Data on antibodies against MPXV induced by historic smallpox vaccination in people with HIV are scarce. In this observational study, plasma samples were collected from people living with and without HIV in Shenzhen, China. We measured antibodies binding to two representative proteins of vaccinia virus (VACV; A27L and A33R) and homologous proteins of MPXV (A29L and A35R) using an enzyme-linked immunosorbent assay. We compared the levels of these antibodies between people living with and without HIV. Stratified analyses were performed based on the year of birth of 1981 when the smallpox vaccination was stopped in China. Plasma samples from 677 people living with HIV and 746 people without HIV were tested. A consistent pattern was identified among the four antibodies, regardless of HIV status. VACV antigen-reactive and MPXV antigen-reactive antibodies induced by historic smallpox vaccination were detectable in the people born before 1981, and antibody levels reached a nadir during or after 1981. The levels of smallpox vaccine-induced antibodies were comparable between people living with HIV and those without HIV. Our findings suggest that the antibody levels against MPXV decreased in both people living with and without HIV due to the cessation of smallpox vaccination.

To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific antibodies are endowed with the capacity to neutralize Mpox virus (MPXV) in vitro. To test a possible role of polyclonal non-specific activation in the maintenance of immunologic memory.
Sera were collected from the following groups: smallpox-vaccinated individuals with or without latent tuberculosis infection (LTBI), unvaccinated donors, and convalescent individuals after MPXV infection. Supernatant of VV- or MPXV-infected Vero cells were inactivated and used as antigens in ELISA or in Western blot (WB) analyses. An MPXV plaque reduction neutralization test (PRNT) was optimized and performed on study samples. VV- and PPD-specific memory T cells were measured by flow cytometry.
None of the smallpox unvaccinated donors tested positive in ELISA or WB analysis and their sera were unable to neutralize MPXV in vitro. Sera from all the individuals convalescing from an MPXV infection tested positive for anti-VV or MPXV IgG with high titers and showed MPXV in vitro neutralization capacity. Sera from most of the vaccinated individuals showed IgG anti-VV and anti-MPXV at high titers. WB analyses showed that positive sera from vaccinated or convalescent individuals recognized both VV and MPXV antigens. Higher VV-specific IgG titer and specific T cells were observed in LTBI individuals.
ELISA and WB performed using supernatant of VV- or MPXV-infected cells are suitable to identify individuals vaccinated against smallpox at more than 45 years from immunization and individuals convalescing from a recent MPXV infection. ELISA and WB results show a good correlation with PRNT. Data confirm that a smallpox vaccination induces a long-lasting memory in terms of specific IgG and that antibodies raised against VV may neutralize MPXV in vitro. Finally, higher titers of VV-specific antibodies and higher frequency of VV-specific memory T cells in LTBI individuals suggest a role of polyclonal non-specific activation in the maintenance of immunologic memory.

After the eradication of smallpox in China in 1979, vaccination with the vaccinia virus (VACV) Tiantan strain for the general population was stopped in 1980. As the monkeypox virus (MPXV) is rapidly spreading in the world, we would like to investigate whether the individuals with historic VACV Tiantan strain vaccination, even after more than 40 years, could still provide ELISA reactivity and neutralizing protection; and whether the unvaccinated individuals have no antibody reactivity against MPXV at all.
We established serologic ELISA to measure the serum anti-MPXV titer by using immunodominant MPXV surface proteins, A35R, B6R, A29L, and M1R. A small proportion of individuals (born before 1980) with historic VACV Tiantan strain vaccination exhibited serum ELISA cross-reactivity against these MPXV surface proteins. Consistently, these donors also showed ELISA seropositivity and serum neutralization against VACV Tiantan strain. However, surprisingly, some unvaccinated young adults (born after 1980) also showed potent serum ELISA activity against MPXV proteins, possibly due to their past infection by some self-limiting Orthopoxvirus (OPXV).
We report the serum ELISA cross-reactivity against MPXV surface protein in a small proportion of individuals both with and without VACV Tiantan strain vaccination history. Combined with our serum neutralization assay against VACV and the recent literature about mice vaccinated with VACV Tiantan strain, our study confirmed the anti-MPXV cross-reactivity and cross-neutralization of smallpox vaccine using VACV Tiantan strain. Therefore, it is necessary to restart the smallpox vaccination program in high risk populations.

The eradication of smallpox and the cessation of vaccination have led to the growth of the susceptible human population to poxviruses. This has led to the increasing detection of zoonotic orthopoxviruses. Among those viruses, monkeypox virus (MPV) is the most commonly detected in Western and Central African regions. Since 2022, MPV is causing local transmission in newly affected countries all over the world. While the virus causing the current outbreak remains part of clade II (historically referred to as West African clade), it has a significant number of mutations as compared to other clade II sequences and is therefore referred to as clade IIb. It remains unclear whether those mutations may have caused a change in the virus phenotype. Vaccine effectiveness data show evidence of a high cross-protection of vaccines designed to prevent smallpox against mpox. These vaccines therefore represent a great opportunity to control human-to-human transmission, provided that their availability has short time-frames and that mistakes from the recent past (vaccine inequity) will not be reiterated.

Mpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. Following historic success of smallpox vaccination with vaccinia virus (VACV)-based vaccines, the third generation modified vaccinia Ankara (MVA)-based vaccine was used as prophylaxis for MPXV, but its effectiveness remains poorly characterized. Here, we applied two assays to quantify neutralizing antibodies (NAbs) in sera from control, MPXV-infected, or MVA-vaccinated individuals. Various levels of MVA NAbs were detected after infection, historic smallpox, or recent MVA vaccination. MPXV was minimally sensitive to neutralization. However, addition of complement enhanced detection of responsive individuals and NAb levels. Anti-MVA and -MPXV NAbs were observed in 94% and 82% of infected individuals, respectively, and 92% and 56% of MVA vaccinees, respectively. NAb titers were higher in individuals born before 1980, highlighting the impact of historic smallpox vaccination on humoral immunity. Altogether, our results indicate that MPXV neutralization is complement dependent and uncover mechanisms underlying vaccine effectiveness.

UNASSIGNED: The presentation of mpox clade IIb during the 2022 outbreak overlaps with a range of other diseases. Understanding the factors associated with mpox is important for clinical decision making.
UNASSIGNED: We described the characteristics of mpox patients who sought care at Belgian sexual health clinic. Furthermore we compared their characteristics to those of patients with a clinical suspicion of mpox but who tested negative on polymerase chain reaction.
UNASSIGNED: Between May 23 and September 20, 2022, 155 patients were diagnosed with mpox, and 51 patients with suspected symptoms tested negative. All mpox patients self-identified as men and 148/155 (95.5%) as gay or bisexual MSM. Systemic symptoms were present in 116/155 (74.8%) patients. All but 10 patients (145/155, 93.5%) presented with skin lesions. Other manifestations were lymphadenopathy (72/155, 46.5%), proctitis (50/155, 32.3%), urethritis (12/155, 7.7%), tonsillitis (2/155, 1.3%). Complications involved bacterial skin infection (13/155, 8.4%) and penile oedema with or without paraphimosis (4/155, 2.6%). In multivariable logistic regression models, the presence of lymphadenopathy (OR 3.79 95% CI 1.44-11.49), skin lesions (OR 4.35 95% CI 1.15-17.57) and proctitis (OR 9.41 95% CI 2.72-47.07) were associated with the diagnosis of mpox. There were no associations with age, HIV status, childhood smallpox vaccination, number of sexual partners and international travel.
UNASSIGNED: The presence of proctitis, lymphadenopathies and skin lesions should increase clinical suspicion of mpox in patients with compatible symptoms.

OBJECTIVE: The worldwide mpox outbreak starting in May 2022 marks the occurrence of another previously atypical infectious disease in Europe. This study\'s objective was to present a comprehensive overview based on the gathered data and to illustrate the approach of the Cologne Health Department to contain the mpox outbreak.
METHODS: In this retrospective observational study, 368 individuals reported to the Cologne Health Department as PCR-positive for mpox were included. Data were collected in structured telephone interviews and digitally processed.
RESULTS: The first mpox case in Cologne was recorded on May 24, 2022. The local outbreak lasted approximately 4 months and reached its peak in July. The last reported case in Cologne occurred on September 17. Transmissions mostly occurred through sexual contacts (67.4%) or other close physical contacts (4.6%) between men, but also through fomites, in the context of events or occasionally in the work environment. In 21.5% of cases, no route of infection could be determined. The mean incubation period was 8.2 days. Clinically, mpox infections usually presented with skin and/or mucosal lesions accompanied by general symptoms. In 74.8% of cases, a prodromal stage was absent. Initially, the rash often had an unspecific appearance, but in the further clinical course, it usually passed through the typical stages. Most infections resolved spontaneously under home care. In 3.5% of cases, however, inpatient hospitalisation was required. Infected persons with a previous smallpox vaccination had 0.43 times the odds of unvaccinated persons to be affected by lesions in 3 or more body regions and 0.30 times the odds to develop lesions in all 5 body regions. Previous vaccination statistically reduced the total duration of symptoms by 2.0 days.
CONCLUSIONS: The mpox outbreak 2022 in Cologne primarily affected men who have sex with men and have reported recent sexual encounters. The observed average incubation period was shorter than initially assumed. Mucosal involvement and associated symptoms occur in a relevant number of cases and can lead to more severe clinical courses. Previous smallpox vaccination was statistically significantly associated with milder courses of mpox. In the case of an unclear rash or symptoms suggesting mucosal involvement, mpox should be considered as a differential diagnosis. An equally rapid and well-orchestrated public health response are crucial for infection control.

Monkeypox (MPVX) infection has been associated with multiorgan presentations. Thus, monkeypox infection\'s early and late complications are of particular concern, prompting health systems to decipher threatening sequels and their possible countermeasures. The current article will review the clinical signs and symptoms of the present and former outbreaks, differential diagnoses, workup and treatment of the ocular manifestations of MPXV infection in detail. One of the uncommon yet considerable MPXV complications is ocular involvement. These injuries are classified as (1) more frequent and benign lesions and (2) less common and vision-threatening sequels. Conjunctivitis, blepharitis and photophobia are the most uncomplicated reported presentations. Moreover, MPXV can manifest as eye redness, frontal headache, orbital and peri-ocular rashes, lacrimation and ocular discharge, subconjunctival nodules and, less frequently, as keratitis, corneal ulceration, opacification, perforation and blindness. The ocular manifestations have been less frequent and arguably less severe within the current outbreak. Despite the possibility of underestimation, the emerging evidence from observational investigations documented rates of around 1% for ocular involvement in the current outbreak compared to a 9-23% incidence in previous outbreaks in the endemic countries. The history of smallpox immunization is a protective factor against these complications. Despite a lack of definite and established treatment, simple therapies like regular lubrication and prophylactic use of topical antibiotics may be considered for MPXV ocular complications. Timely administration of specific antivirals may also be effective in severe cases. Monkeypox usually has mild to moderate severity and a self-limited course. However, timely recognition and proper management of the disease could reduce the risk of permanent ocular sequelae and disease morbidity.

Monkeypox virus (MPXV) was declared by the World Health Organization (WHO) in mid-2022 to be a public health emergency of international concern, following its spread around the world after circulating in Western and Central Africa. This new outbreak is concentrated in men who have sex with men (MSM). Moreover, beyond the epidemiological change, compared with endemic countries, differences in clinical features and many other aspects have also been detected. These and other characteristics are unusual and still unclear. Based on the available data, the authors try to help to clarify some of the current major gaps in monkeypox knowledge to strengthen the outbreak response.