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

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

Cross-reactive antibodies against monkeypox virus exist in the population immunized with vaccinia Tian Tan strain in China.

Monkeypox virus (MPXV) belongs to the Orthopoxvirus genus. The worldwide outbreak of MPXV in 2022 has caused widespread concerns. Cross-reactive antibodies induced by vaccinia-inoculation can provide protection against reinfection by MPXV. The vaccinia Tian Tan (VTT) strain, which was widely inoculated in the Chinese population before the 1980s, has genomic differences from other vaccinia strains, although they all belong to the orthopoxviruses family. The current seroprevalence of VTT-vaccinated populations remains unclear more than four decades after the termination of vaccination campaigns in China. Our results showed that cross-reactive IgG antibodies against MPXV were present in 31.8% (75/236) of vaccinees four decades after VTT-vaccination, suggesting that vaccination with VTT may provide long-term protection against MPXV infection in some individuals.

Orthopoxvirus Circulation in an Endemic Area in Brazil: Investigation of Infections in Small Mammals during an Absence of Outbreaks.

Vaccinia virus (VACV) is the causative agent of an emerging viral zoonosis called bovine vaccinia (BV). Several studies have documented characteristics of VACV infections in Brazil; however, the manner in which this virus is maintained in wildlife remains unknown. This work investigated the presence of viral DNA and anti-orthopoxvirus (OPXV) antibodies in samples collected from small mammals in a VACV-endemic area in Minas Gerais, Brazil, in the absence of current outbreaks. Samples did not show amplification of OPXV DNA in molecular tests. However, 5/142 serum samples demonstrated the presence of anti-OPXV neutralizing antibodies in serological tests. These data reinforce the involvement of small mammals in the natural cycle of VACV, highlighting the need for further ecological studies to better understand how this virus is maintained in nature and to develop measures to prevent BV outbreaks.

Interferon α/ß Decoy Receptor Encoded by a Variant in the Dryvax Smallpox Vaccine Contributes to Virulence and Correlates with Severe Vaccine Side Effects.

Although providing long-lasting immunity, smallpox vaccination was associated with local and systemic reactions and rarely with severe complications, including progressive vaccinia and postvaccinia encephalitis. As the Dryvax smallpox vaccine consists of a population of variants, we investigated a particularly pathogenic isolate called clone 3 (CL3). Virus replication was monitored by inserting the gene encoding firefly luciferase (Luc) into the genomes of CL3 and ACAM2000, the second-generation smallpox vaccine derived from a less virulent clone. Greater luminescence occurred following intranasal or intraperitoneal inoculation of mice with CL3-Luc than ACAM2000-Luc. Previous genome sequencing of CL3 and ACAM2000 revealed numerous differences that could affect pathogenicity. We focused on a 4.2-kbp segment, containing several open reading frames, in CL3 that is absent from ACAM2000 and determined that lower virulence of the latter was associated with a truncation of the interferon α/ß (IFN-α/ß) decoy receptor. Truncation of the decoy receptor in CL3-Luc and repair of the truncated version in ACAM2000-Luc decreased and increased virulence, respectively. Blockade of the mouse type 1 IFN receptor increased the virulence of ACAM2000-Luc to that of CL3-Luc, consistent with the role of IFN in attenuating the former. The severities of disease following intracranial inoculation of immunocompetent mice and intraperitoneal inoculation of T cell-depleted mice were also greater in viruses expressing the full-length decoy receptor. Previous evidence for the low affinity of a similarly truncated decoy receptor for IFN and the presence of a full-length decoy receptor in virus isolated from a patient with progressive vaccinia support our findings. IMPORTANCE Attenuated live viruses make effective vaccines, although concerns exist due to infrequent complications, particularly in individuals with immunological defects. Such complications occurred with smallpox vaccines, which were shown to be comprised of populations of variants. Clone 3, isolated from Dryvax, the vaccine most widely used in the United States during the smallpox eradication campaign, was particularly pathogenic in animal models. We demonstrated that the full-length IFN-α/ß decoy receptor in CL3 and a truncation of the receptor in the clone used for the second-generation smallpox vaccine ACAM2000 account for their difference in pathogenicity. Viruses expressing the full-length decoy receptor were more virulent following intranasal, intraperitoneal, or intracranial inoculation of mice than ACAM2000, and disease was exacerbated following T cell depletion. Correspondingly, the full-length decoy receptor is present in smallpox vaccines with high rates of side effects and in a Dryvax clone obtained from a lesion in a patient with progressive vaccinia.

Seroprevalence of bovine vaccinia in cows and its correlation with the productive profile of affected farms in Distrito Federal, Brazil.

Bovine vaccinia (BV) is an infectious disease caused by Vaccinia virus (VACV) characterized by vesicular and exanthematic lesions, mainly in cattle. Although BV has been described in some Brazilian regions in the last decades, official information regarding the current prevalence in bovine herds of Midwestern Brazil is lacking. Thus, the current study aimed to estimate the seroprevalence and risk factors associated with BV in cattle in the Distrito Federal (DF), Brazil. Sera of 312 cows of 64 herds were tested by virus-neutralizing test for VACV antibodies. Herd and animal seroprevalence were estimated to be 33.3% (CI 95%: 18.2-48.3%) and 10.6% (CI 95%: 1.0-20.2%), respectively. Seropositive cows were detected in dairy, beef, and mixed-purpose farms. The results of an epidemiological questionnaire showed that no risk factor analyzed was positively associated with seropositivity to VACV. There was no significant association between type of milking (manual/mechanic) and seropositivity to VACV; however, most seropositive cows were present in farms with high daily milk production and high number of lactating and adult cows. Our results indicate that VACV circulates in many regions of DF with considerable prevalence in dairy cows. Control measures to restrict VACV circulation and consequences of the infection may be advisable.

Buffalopox Disease in Livestock and Milkers, India.

Buffalopox outbreaks caused by vaccinia virus were observed in villages of Tamil Nadu, India, among lactating buffaloes and cows. Milkers also had lesions on their fingers. Because vaccinia virus is known to have extended its host range in Brazil, we recommend continuous surveillance to understand cross-species transmission and to curtail disease effects.

Genomic diversity of vaccinia virus strain Cantagalo isolated in southeastern Brazil during the early years of the outbreak, 1999-2006.

Outbreaks of a vesiculopustular disease in dairy cattle and milkers have been frequently reported in Brazil since 1999 when the vaccinia virus strain Cantagalo was first isolated in the State of Rio de Janeiro. However, the genomic diversity of the viral isolates associated with these outbreaks is not well known, particularly in the southeastern states that represent the focal point of virus spread to other regions. Here, we report the genomic sequences and an analysis of the polymorphic site profiles and genotypic diversity of four clinical isolates of vaccinia virus strain Cantagalo collected from 1999 to 2006 in southeastern Brazil.

Poxviruses diagnosed in cattle from Distrito Federal, Brazil (2015-2018).

A retrospective study of officially diagnosed poxvirus infections in cattle in Distrito Federal (DF), Brazil, between 2015 and 2018 was performed. All cases were investigated by the DF Official Veterinary Service. In the most cases, samples of oral, cutaneous (teats, udder) or foot lesions were submitted to molecular diagnosis by PCR. In approximately 70% of the cases, additional samples were also submitted for histopathology. Ninety-three out of 2,467 clinically examined cattle (from 385 farms) presented suggestive and/or compatible lesions with poxviruses. Fifty-two out of these 93 cases were confirmed as poxviruses: 27 vaccinia virus (VACV), 9 pseudocowpox virus (PCPV), 8 bovine papular stomatitis virus (BPSV), 5 coinfection by PCPV and BPSV and 3 unidentified parapoxvirus. The clinical cases were observed in farms with different exploration (beef, dairy or mixed) from 9 out of 30 administrative regions of DF. Gross findings consisted of papules, vesicles, ulcers, scabs and scars and varied of type, severity and affected tissue, according to the detected virus. A single human case was observed associated with a BPSV infection. Histologically, the lesions were very similar, independently of the detected poxvirus, and included mild to moderate, superficial, multifocal inflammatory infiltrate of lymphocytes, plasma cells, macrophages and/or neutrophils, with acanthosis and parakeratotic hyperkeratosis, usually associated with serous content, cellular debris and spongiosis. In the ulcerated lesions, there were focally extensive areas of necrosis with severe infiltrate of neutrophils in the adjacent connective tissue. Few to moderate amount of 4- to 8-µm eosinophilic inclusion bodies were observed in the cytoplasm of keratinocytes in 6 cases (2 of VACV, 2 of PCPV and 2 of PCPV/BPSV coinfection). Data of the current study demonstrate the wide circulation of different poxviruses in cattle from DF.

Exposure of free-ranging capybaras (Hydrochoerus hydrochaeris) to the vaccinia virus.

The aim of this study was to evaluate the possibility of free-ranging animals/hunting dogs as sources of infection in the vaccinia virus (VACV) transmission chain. Serological, cell culture and molecular assays were conducted in 56 free-ranging animals and 22 hunting dogs. ELISA/neutralizing assays showed that two (2.5%) capybaras (Hydrochoerus hydrochaeris) had anti-OPV positive antibodies, while all samples tested negative through PCR/cell culture. After being hit by cars on roads, capybaras that exhibited neither clinical signs nor any association with bovine outbreaks had neutralizing antibodies against the Orthopoxvirus, as detected through plaque-reduction neutralizing tests and ELISA. Evidence exists regarding peridomestic capybaras acting as a source of the virus and serving as a link between wild and urban environments, thus contributing to viral maintenance.

Genomic diversity of vaccinia virus strain Cantagalo isolated in southeastern Brazil during the early years of the outbreak, 1999-2006

Outbreaks of a vesiculopustular disease in dairy cattle and milkers have been frequently reported in Brazil since 1999 when the vaccinia virus strain Cantagalo was first isolated in the State of Rio de Janeiro. However, the genomic diversity of the viral isolates associated with these outbreaks is not well known, particularly in the southeastern states that represent the focal point of virus spread to other regions. Here, we report the genomic sequences and an analysis of the polymorphic site profiles and genotypic diversity of four clinical isolates of vaccinia virus strain Cantagalo collected from 1999 to 2006 in southeastern Brazil.

Seroprevalence and Risk Factors Possibly Associated with Emerging Zoonotic Vaccinia Virus in a Farming Community, Colombia.

In 2014, vaccinia virus (VACV) infections were identified among farmworkers in Caquetá Department, Colombia; additional cases were identified in Cundinamarca Department in 2015. VACV, an orthopoxvirus (OPXV) used in the smallpox vaccine, has caused sporadic bovine and human outbreaks in countries such as Brazil and India. In response to the emergence of this disease in Colombia, we surveyed and collected blood from 134 farmworkers and household members from 56 farms in Cundinamarca Department. We tested serum samples for OPXV antibodies and correlated risk factors with seropositivity by using multivariate analyses. Fifty-two percent of farmworkers had OPXV antibodies; this percentage decreased to 31% when we excluded persons who would have been eligible for smallpox vaccination. The major risk factors for seropositivity were municipality, age, smallpox vaccination scar, duration of time working on a farm, and animals having vaccinia-like lesions. This investigation provides evidence for possible emergence of VACV as a zoonosis in South America.

Outbreak of Vaccinia Virus Infection from Occupational Exposure, China, 2017.

Human infections with vaccinia virus (VACV), mostly from laboratory accidents or contact with infected animals, have occurred since smallpox was eradicated in 1980. No recent cases have been reported in China. We report on an outbreak of VACV from occupational exposure to rabbit skins inoculated with VACV.

Vaccinia Virus in Blood Samples of Humans, Domestic and Wild Mammals in Brazil.

Outbreaks of Vaccinia virus (VACV) affecting cattle and humans have been reported in Brazil in the last 15 years, but the origin of outbreaks remains unknown. Although VACV DNA have been already detected in mice (Mus musculus), opossums (Didelphis albiventris) and dogs during VACV zoonotic outbreaks, no transmission to cattle or humans from any of these were reported during Brazilian outbreaks. In this work, we assessed the PCR positivity to VACV in blood samples of cows and other domestic mammals, wild rodents and other wild mammals, and humans from areas with or without VACV infection reports. Our results show the detection of VACV DNA in blood samples of cows, horse and opossums, raising important questions about VACV spread.

[Zoonotic vaccinia in Colombia: Cumulative evidence of the emergence of poxviruses in the world]. / Vaccinia zoonótica en Colombia: evidencia acumulativa de la emergencia de los poxvirus en el mundo.

The recent occurrence of vaccinia virus infections in humans and animals in Colombia, together with that reported for this and other species of the genus Orthopoxvirus in some South American, African, Asian and European countries, is supporting evidence of the emergence and re-emergence of the genus. This fact has become of great interest for public health around the world due to its biological and an epidemiological features, as was in the past the variola virus, one of its representatives. The emergence and re-emergence of the genus Orthopoxvirus may be a consequence of stopping vaccination against the variola virus in the 1970s and 1980s. This vaccination unsuspectedly induced cross-protective immunity to other species of that genus. This is a review of the history, biology and epidemiology of the main species of the genus Orthopoxvirus, together with its clinical presentation, social context and public health impact in the past, present and future.

La reciente ocurrencia de infecciones por el virus vaccinia en animales y humanos en distintos lugares de la geografía colombiana, sumadas a otras por éste y por otros virus pertenecientes al género Orthopoxvirus (familia Poxviridae), ocurridas en algunos países de Suramérica, África, Asia y Europa se convierten en evidencia de la inminente emergencia y re-emergencia de este género, con características biológicas y epidemiológicas que le confieren gran interés para la salud pública del mundo, como lo fue en el pasado una de sus especies representativas: el virus de la viruela. Esta emergencia y re-emergencia parecen estar relacionadas con la suspensión en las décadas de los 70s y 80s de las campañas de vacunación contra la viruela, las cuales; insospechadamente estuvieron protegiendo a la población, no únicamente contra este virus, sino contra otros del mismo género. En el presente artículo se hace una revisión de la biología y epidemiología de los principales miembros del género Orthopoxvirus, su presentación clínica, antecedentes históricos, contexto social, e impacto en la salud pública mundial en el pasado, presente y a futuro.

Ocular Vaccinia Infection in Dairy Worker, Brazil.

We studied a clinical case of vaccinia virus that caused an ocular manifestation in a dairy worker in Brazil. Biologic and molecular analyses identified a co-infection with 2 isolates from different Brazilian vaccinia virus phylogenetic groups.

Vaccinia Virus Natural Infections in Brazil: The Good, the Bad, and the Ugly.

The orthopoxviruses (OPV) comprise several emerging viruses with great importance to human and veterinary medicine, including vaccinia virus (VACV), which causes outbreaks of bovine vaccinia (BV) in South America. Historically, VACV is the most comprehensively studied virus, however, its origin and natural hosts remain unknown. VACV was the primary component of the smallpox vaccine, largely used during the smallpox eradication campaign. After smallpox was declared eradicated, the vaccination that conferred immunity to OPV was discontinued, favoring a new contingent of susceptible individuals to OPV. VACV infections occur naturally after direct contact with infected dairy cattle, in recently vaccinated individuals, or through alternative routes of exposure. In Brazil, VACV outbreaks are frequently reported in rural areas, affecting mainly farm animals and humans. Recent studies have shown the role of wildlife in the VACV transmission chain, exploring the role of wild rodents as reservoirs that facilitate VACV spread throughout rural areas. Furthermore, VACV circulation in urban environments and the significance of this with respect to public health, have also been explored. In this review, we discuss the history, epidemiological, ecological and clinical aspects of natural VACV infections in Brazil, also highlighting alternative routes of VACV transmission, the factors involved in susceptibility to infection, and the natural history of the disease in humans and animals, and the potential for dissemination to urban environments.

Ecological niche modeling to determine potential niche of Vaccinia virus: a case only study.

BACKGROUND: Emerging and understudied pathogens often lack information that most commonly used analytical tools require, such as negative controls or baseline data; thus, new analytical strategies are needed to analyze transmission patterns and drivers of disease emergence. Zoonotic infections with Vaccinia virus (VACV) were first reported in Brazil in 1999, VACV is an emerging zoonotic Orthopoxvirus, which primarily infects dairy cattle and farmers in close contact with infected cows. Prospective studies of emerging pathogens could provide critical data that would inform public health planning and response to outbreaks. By using the location of 87-recorded outbreaks and publicly available bioclimatic data, we demonstrate one such approach. Using an ecological niche model (ENM) algorithm, we identify the environmental conditions under which VACV outbreaks have occurred, and determine additional locations in two affected countries that may be susceptible to transmission. Further, we show how suitability for the virus responds to different levels of various environmental factors and highlight the most important factors in determining its transmission. METHODS: A literature review was performed and the geospatial coordinates of 87 molecularly confirmed VACV outbreaks in Brazil were identified. An ENM was generated using MaxENT software by combining principal component analysis results of 19 bioclim spatial layers, and 25 randomly selected subsets of the original list of 87 outbreaks. RESULTS: The final ENM predicted all areas where Brazilian outbreaks occurred, one out of five of the Colombian outbreak regions and identified new regions within Brazil that are suitable for transmission based on bioclimatic factors. Further, the most important factors in determining transmission suitability are precipitation of the wettest quarter, annual precipitation, mean temperature of the coldest quarter and mean diurnal range. CONCLUSION: The analyses here provide a means by which to study patterns of an emerging infectious disease and identify regions that are potentially suitable for its transmission, in spite of the paucity of high-quality critical data. Policy and methods for the control of infectious diseases often use a reactionary model, addressing diseases only after significant impact on human health has ensued. The methodology used in the present work allows the identification of areas where disease is likely to appear, which could be used for directed intervention.

Subclinical bovine vaccinia: An important risk factor in the epidemiology of this zoonosis in cattle.

Bovine vaccinia (BV) is a zoonosis caused by Vaccinia virus (VACV) that mainly affects lactating cows and dairy farm milkers. The epidemiological role(s) of other cattle categories such as dry cows, bulls, and heifers in BV remains unclear. This study was performed to investigate VACV in affected dairy cattle herds and perifocal farms during an outbreak in Brazil. Crusts from lesions of cows' teats were collected from all farms with BV outbreaks. Milk, feces, blood, and serum were collected from symptomatic and asymptomatic lactating cows. Blood and serum were also sampled from other cattle categories (calves, heifers, dry cows, and bulls). The samples were tested for VACV by PCR, and to confirm VACV viability, VACV-positive samples were inoculated in BSC-40 cells and stained using immunoperoxidase. Neutralizing antibodies were investigated using plaque reduction neutralization test. Viral DNA was detected in milk, blood, and feces samples of symptomatic and asymptomatic dairy cows and in blood samples from other cattle categories on farms with and without confirmed BV outbreak. In affected farms, viable virus was identified in feces and milk samples from lactating cows and in blood samples from asymptomatic dry cows. Viable VACV was also identified in feces from lactating cows and one bull's blood sample from perifocal farms. Neutralizing antibodies were detected in 81.6% of the herds affected by BV and in 53.8% of the herds on perifocal farms. The presented data indicate a potential source of viral dissemination, which contributes to the persistence and spread of VACV in the environment.

Serologic and Molecular Evidence of Vaccinia Virus Circulation among Small Mammals from Different Biomes, Brazil.

Vaccinia virus (VACV) is a zoonotic agent that causes a disease called bovine vaccinia, which is detected mainly in milking cattle and humans in close contact with these animals. Even though many aspects of VACV infection have been described, much is still unknown about its circulation in the environment and its natural hosts/reservoirs. To investigate the presence of Orthopoxvirus antibodies or VACV DNA, we captured small rodents and marsupials in 3 areas of Minas Gerais state, Brazil, and tested their samples in a laboratory. A total of 336 animals were tested; positivity ranged from 18.1% to 25.5% in the 3 studied regions located in different biomes, including the Atlantic Forest and the Cerrado. Analysis of nucleotide sequences indicated co-circulation of VACV groups I and II. Our findings reinforce the possible role played by rodents and marsupials in VACV maintenance and its transmission chain.