Breakthrough Mpox Outbreak Investigation, the Delicate Balance Between Host Immune Response and Viral Immune Escape.

BACKGROUND: Limited data are available on Mpox breakthrough infections. PURPOSE: The purpose of this study is to investigate a Mpox breakthrough outbreak in 3 vaccinated individuals. METHODS: Study participants provided informed consent. Serology testing was performed in one involved individual (ID-1) using an in-house assay detecting anti-orthopoxvirus IgG. Whole genome sequencing (WGS) was carried out and compared with the reference sequence ON563414.3 ( https://www.ncbi.nlm.nih.gov/nuccore/ON563414.3/ ). RESULTS: Three individuals vaccinated with modified vaccinia Ankara-Bavaria Nordic contracted Mpox following one sexual intercourse event. One of them (ID-1) had received only one vaccine dose, while the other two were fully vaccinated. ID-1 presented to the sexual health clinic of the Universitair Ziekenhuis Brussel with proctitis related to Mpox. Despite one vaccination, serology testing Three months post vaccine showed absence of Mpox virus (MPXV) specific antibodies in ID-1. In contrast, 2 weeks after the sexual intercourse, seroconversion occurred. Whole genome sequencing of the isolated MPXV showed, compared with the reference sequence, a total of seven single nucleotide variants with four of them indicating protein amino-acid changes. CONCLUSION: Incomplete MPXV vaccination as well as MPXV variants might result in breakthrough infections. Preventive measures, such as MPVX vaccination, could maintain immunity in individuals with higher risk of MPXV infection, and might lower disease severity.

Immune interactions and heterogeneity in transmission drives the pathogen-mediated invasion of grey squirrels in the UK.

Mathematical models highlighted the importance of pathogen-mediated invasion, with the replacement of red squirrels by squirrelpox virus (SQPV) carrying grey squirrels in the UK, a well-known example. In this study, we combine new epidemiological models, with a range of infection characteristics, with recent longitudinal field and experimental studies on the SQPV dynamics in red and grey squirrel populations to better infer the mechanistic basis of the disease interaction. A key finding is that a model with either partial immunity or waning immunity and reinfection, where individuals become seropositive on the second exposure to infection, that up to now has been shown in experimental data only, can capture the key aspects of the field study observations. By fitting to SQPV epidemic observations in isolated red squirrel populations, we can infer that SQPV transmission between red squirrels is significantly (4×) higher than the transmission between grey squirrels and as a result our model shows that disease-mediated replacement of red squirrels by greys is considerably more rapid than replacement in the absence of SQPV. Our findings recover the key results of the previous model studies, which highlights the value of simple strategic models that are appropriate when there are limited data, but also emphasise the likely complexity of immune interactions in wildlife disease and how models can help infer disease processes from field data.

Tracing the journey of poxviruses: insights from history.

The historical significance of the poxviruses is profound, largely due to the enduring impact left by smallpox virus across many centuries. The elimination of smallpox is a remarkable accomplishment in the history of science and medicine, with centuries of devoted efforts resulting in the development and widespread administration of smallpox vaccines. This review provides insight into the pivotal historical events involving medically significant poxviruses. Understanding the remarkable saga of combatting smallpox is crucial, serving as a guidepost for potential future encounters with poxvirus infections. There is a continual need for vigilant observation of poxvirus evolution and spillover from animals to humans, considering the expansive range of susceptible hosts. The recent occurrence of monkeypox cases in non-endemic countries stands as a stark reminder of the ease with which infections can be disseminated through international travel and trade. This backdrop encourages introspection about our journey and the current status of poxvirus research.

Prevalence, clinico-epidemiological features, and molecular characterization of bovine papular stomatitis virus in cattle in Iraq.

Bovine papular stomatitis virus (BPSV) is a parapoxvirus that infects cattle, causing skin lesions on the udder and mouth. There have been few studies on the prevalence and molecular characteristics of BPSV in Iraq. Here, we describe the prevalence, phylogenetic analysis, and clinico-epidemiological features of BPSV in cattle in Al-Qadisiyah, Iraq. A total of 264 animals were examined for teat and oral lesions, and BPSV was detected by PCR in 79.9% (211/264) of cattle and calves with skin lesions. The lesions included ulcers, papules, and scabby proliferative areas. The BPSV strains from Iraq clustered phylogenetically with BPSV strains detected in the USA. Further studies are needed to explore the evolution and epidemiology of this virus in the region.

Poxviruses in Children.

The family Poxviridae is a large family of viruses with a ubiquitous distribution, subdivided into two subfamilies: Chordopoxvirinae (poxviruses of vertebrates) and Entomopoxvirinae (poxviruses of insects). Only three species from the first subfamily, Orthopoxvirus (OPV), Molluscipoxvirus and Parapoxvirus, can infect the human being. In the paediatric population, viruses belonging to the first two subfamilies have the greatest importance. Following the eradication of smallpox in 1980, vaccination of the general population was discontinued after careful consideration of the risks and benefits. However, nearly all children and most of the world's population had little to no protection against OPV. The aim of this chapter is to review the current evidence on the aetiology, clinical manifestations, diagnosis and management of Poxviridae infections in children.

Poxvirus Vaccines: Past, Present, and Future.

Smallpox was a significant cause of mortality for over three thousand years, amounting to 10% of deaths yearly. Edward Jenner discovered smallpox vaccination in 1796, which rapidly became a smallpox infection preventive practice throughout the world and eradicated smallpox infection by 1980. After smallpox eradication, monkeypox vaccines have been used primarily in research and in outbreaks in Africa, where the disease is endemic. In the present, the vaccines are being used for people who work with animals or in high-risk areas, as well as for healthcare workers treating patients with monkeypox. Among all orthopoxviruses (OPXV), monkeypox viral (MPXV) infection occurs mainly in cynomolgus monkeys, natural reservoirs, and occasionally causes severe multi-organ infection in humans, who were the incidental hosts. The first case of the present epidemic of MXPV was identified on May 7, 2022, and rapidly increased the number of cases. In this regard, the WHO declared the outbreak, an international public health emergency on July 23, 2022. The first monkeypox vaccine was developed in the 1960s by the US Army and was based on the vaccinia virus, which is also used in smallpox vaccines. In recent years, newer monkeypox vaccines have been developed based on other viruses such as Modified Vaccinia Ankara (MVA). These newer vaccines are safer and can provide longer-lasting immunity with fewer side effects. For the future, there is ongoing research to improve the current vaccines and to develop new ones. One notable advance has been the development of a recombinant vaccine that uses a genetically modified vaccinia virus to express monkeypox antigens. This vaccine has shown promising results in pre-clinical trials and is currently undergoing further testing in clinical trials. Another recent development has been the use of a DNA vaccine, which delivers genetic material encoding monkeypox antigens directly into cells. This type of vaccine has shown effectiveness in animal studies and is also undergoing clinical testing in humans. Overall, these recent advances in monkeypox vaccine development hold promise for protecting individuals against this potentially serious disease.

Poxviruses from the Concept of One Health.

In the last 4 years, the world has experienced two pandemics of bat-borne viruses. Firstly, in 2019 the SARS-CoV-2 pandemic started and has been causing millions of deaths around the world. In 2022, a Monkeypox pandemic rose in various countries of the world. Those pandemics have witnessed movements and initiatives from healthcare and research institutions to establish a worldwide understanding to battle any future pandemics and biological threats. One Health concept is a modern, comprehensive, unifying ways to improve humans, animals, and ecosystems' health. This concept shows how much they are intertwined and related to one another, whether it is an environmental, or a pathological relation. This review aims to describe Poxviridae and its impact on the One Health concept, by studying the underlying causes of how poxviruses can affect the health of animals, humans, and environments. Reviewing the effect of disease transmission between animal to human, human to human, and animal to animal with pox viruses as a third party to achieve a total understanding of infection and viral transmission. Thus, contributing to enhance detection, diagnosis, research, and treatments regarding the application of One Health.

Molecular characterization of cetacean poxviruses along the coast of mainland Portugal.

Cetacean poxvirus (CePV) is the causative agent of tattoo skin disease (TSD) in dolphins, porpoises and whales, a condition characterized by pinhole, ring-like lesions or generalized tattoo-like skin lesions. This study genetically characterized cetacean poxviruses from stranded animals along mainland Portugal. Samples from skin lesions compatible with TSD were obtained from 4 odontocete species (Delphinus delphis, Stenella coeruleoalba, Phocoena phocoena, and Tursiops truncatus) and analyzed using a conventional PCR assay targeting the DNA polymerase gene partially. Among the positive samples (n = 29, 65.9%), a larger DNA polymerase gene fragment was obtained, allowing a robust phylogenetic analysis. Nineteen samples (43.2%) were successfully amplified and sequenced using Sanger sequencing. By combining 11 of these sequences with those from public databases, a maximum likelihood phylogenetic tree was constructed, revealing high heterogeneity within the group. These findings contribute to a better understanding of the genetic diversity, epidemiology, phylogenetics, and evolution of CePV.

Orthopoxvirus Infections in Rodents, Nigeria, 2018-2019.

To investigate animal reservoirs of monkeypox virus in Nigeria, we sampled 240 rodents during 2018-2019. Molecular (real-time PCR) and serologic (IgM) evidence indicated orthopoxvirus infections, but presence of monkeypox virus was not confirmed. These results can be used to develop public health interventions to reduce human infection with orthopoxviruses.

Spatio-temporal analysis of sheep and goat pox outbreaks in Uganda during 2011-2022.

BACKGROUND: Sheep and goat pox (SGP) caused by sheep poxvirus (SPV) and goat poxvirus (GPV) respectively; are transboundary and World Organisation for Animal Health (WOAH)-notifiable viral diseases. There is barely any coherent information about the distribution and prevalence of SGP for Uganda. We therefore conducted this study to describe the temporal and spatial distribution of SGP suspected outbreaks in Uganda for the period 2011-2020 as well as serologically confirm presence of SGP antibodies in suspected SGP outbreaks reported in 2021-2022. RESULTS: Thirty-seven [37] SGP outbreaks were reported across the country during the study period. North-eastern region [that comprises of Karamoja region] had the highest number of outbreaks [n = 17, 45%]; followed by Central [n = 9, 2.4%], Northern [n = 8, 2.2%] and Western region [n = 3, 0.08%]. Reports from district veterinary personnel indicate that the prevalence of; and mortality rate and case fatality rate associated with SGP were 0.06%, 0.02% and 32% respectively. There was a steady increase in the number of reported SGP outbreaks [x̄ = 4] over the study period. Seropositivity of SGPV antibodies in outbreak sheep and goats that were investigated during the study period [2021-2022] was [n = 41, 27%, 95 CI;] CONCLUSION: Our analyses of SGPV passive and active reports indicate that SGP is present in Uganda with a decade long average of four outbreaks per annum. During this period, about a third of all SGPV-clinically infected animals died. SPG is therefore a major constraint to small ruminant health and productivity in Uganda. Introduction of animals from infected herds and breach in farm biosecurity were the most important predictors of SGP outbreaks. In addition to the already existing SGP commercial vaccines, small ruminant screening for SGPV before introducing them to naïve herds and ensuring on farm biosecurity should be part of the SGP control tool pack for Ugandan small ruminant farmers.

Enhancing diagnostic accuracy in common human poxvirus infections during mpox outbreak: A dermoscopy review.

Poxviruses belong to the Poxviridae family, a group of pathogens known for their high infectivity in humans, posing significant health threats. One of the most well-known representatives of poxvirus infections is smallpox, which has been successfully eradicated. However, in recent years, there has been a resurgence in cases of mpox, another member of the Poxviridae family, raising concerns about the potential for a global pandemic or a worldwide health crisis. While the typical clinical presentation of mpox and other poxvirus infections often involves cutaneous lesions, there have been reports of various atypical and non-classic clinical manifestations. Dermoscopy has emerged as a crucial diagnostic tool, aiding dermatologists in clinical practice to make informed decisions. In this summary, we provide an overview of the clinical and dermoscopic features of representative cutaneous lesions associated with human poxvirus infections, including mpox, orf, milker's nodule, and molluscum contagiosum.

Spatiotemporal and seasonality analysis of sheep and goat pox (SGP) disease outbreaks in Turkey between 2010 and 2019.

Sheep and goat pox (SGP) is a highly infectious disease with a high case fatality rate. It causes serious economic losses and decreases productivity in infected facilities and contact areas. As in many countries of the world, SGP outbreaks reported from Turkey to the World Organization for Animal Health (OIE) continue to threaten animal health. Therefore, studies that will guide the production of effective policies to prevent and control SGP are extremely important. This study aims at evaluating the spatiotemporal distribution of SGP outbreaks by geographical information system (GIS)-based analyses. In accordance with this purpose, spatiotemporal scan analyses were applied to reveal the spatiotemporal distribution pattern and transmission of SGP outbreaks reported in Turkey between 2010 and 2019. Space-time cluster analysis revealed 4 several clusters, indicating geographic areas at the highest risk. Spatiotemporal clusters were 6 to 11 times more likely to be exposed to SGP than the general distribution. The average spatiotemporal density of outbreaks in clusters was estimated as 0.20 ± 0.07 outbreaks per 1000 km2 per month. Seasonal analysis and time series analysis showed similar findings. The seasonality of SGP was mainly defined in the winter (from December to February) when the seasonal adjusted factor (SAF) was at a peak of 504.6. In addition, February had the highest SAF with 7.1. Directional distribution analysis showed that the transmission of SGP was oriented between northeast (NE)-southwest (SW) and northwest (NW)-southeast (SE) and that distribution was changed every 2 years. These findings present a basis for the effective monitoring and prevention of SGP and provide valuable information to policymakers.

The resurgence of a neglected orthopoxvirus: Immunologic and clinical aspects of monkeypox virus infections over the past six decades.

Monkeypox is a zoonotic Orthopoxvirus which has predominantly affected humans living in western and central Africa since the 1970s. Type I and II interferon signaling, NK cell function, and serologic immunity are critical for host immunity against monkeypox. Monkeypox can evade host viral recognition and block interferon signaling, leading to overall case fatality rates of up to 11%. The incidence of monkeypox has increased since cessation of smallpox vaccination. In 2022, a global outbreak emerged, predominantly affecting males, with exclusive human-to-human transmission and more phenotypic variability than earlier outbreaks. Available vaccines are safe and effective tools for prevention of severe disease, but supply is limited. Now considered a public health emergency, more studies are needed to better characterize at-risk populations and to develop new anti-viral therapies.

Are Parapoxvirus zoonotic diseases doomed to remain neglected?

Parapoxvirus (PPV) infections are considered neglected zoonoses because their incidence is often unknown or greatly underestimated despite being endemic globally. Here, we report the comprehensive diagnostic workflow that led to the identification of two cases of persistent PPV infections. The results obtained underline the importance of adopting a "One Health" approach and cross-sectoral collaboration between human and veterinary medicine for precise aetiological diagnosis and correct management of patients affected by zoonotic diseases.

[A grave concern for the prevalence of monkeypox virus].

Monkeypox is a zoonosis caused by monkeypox virus. Monkeypox virus belongs to the Orthopoxviruses genus in the Poxviridae family, which is regarded as the most important Orthopoxvirus infection in human beings after the extinction of smallpox. Since the first human monkeypox case was reported in the Democratic Republic of the Congo in 1970, monkeypox has become endemic in Central and West African. From May 6 to July 15, 2022, monkeypox has broken out in many countries. Monkeypox cases have been detected in 62 countries and regions. Moreover, human to human transmission has occurred and attracted high global attention. Monkeypox virus has been discovered for more than 60 years, but the understanding and research of its natural host, epidemiological characteristics and treatment are still relatively limited. Therefore, this study analyzes the epidemic situation, the possible causes of the outbreak and the future key research directions, and puts forward countermeasures to provide scientific basis for the prevention and control of monkeypox.

First molecular characterization of poxviruses in cattle, sheep, and goats in Botswana.

BACKGROUND: Poxviruses within the Capripoxvirus, Orthopoxvirus, and Parapoxvirus genera can infect livestock, with the two former having zoonotic importance. In addition, they induce similar clinical symptoms in common host species, creating a challenge for diagnosis. Although endemic in the country, poxvirus infections of small ruminants and cattle have received little attention in Botswana, with no prior use of molecular tools to diagnose and characterize the pathogens. METHODS: A high-resolution melting (HRM) assay was used to detect and differentiate poxviruses in skin biopsy and skin scab samples from four cattle, one sheep, and one goat. Molecular characterization of capripoxviruses and parapoxviruses was undertaken by sequence analysis of RPO30 and GPCR genes. RESULTS: The HRM assay revealed lumpy skin disease virus (LSDV) in three cattle samples, pseudocowpox virus (PCPV) in one cattle sample, and orf virus (ORFV) in one goat and one sheep sample. The phylogenetic analyses, based on the RPO30 and GPCR multiple sequence alignments showed that the LSDV sequences of Botswana were similar to common LSDV field isolates encountered in Africa, Asia, and Europe. The Botswana PCPV presented unique features and clustered between camel and cattle PCPV isolates. The Botswana ORFV sequence isolated from goat differed from the ORFV sequence isolated from sheep. CONCLUSIONS: This study is the first report on the genetic characterization of poxvirus diseases circulating in cattle, goats, and sheep in Botswana. It shows the importance of molecular methods to differentially diagnose poxvirus diseases of ruminants.

Geographic distribution and genetic characterization of poxviruses from human infections in Georgia, 2009-2014.

Anthrax is endemic in Georgia, as are multiple zoonotic poxviruses. Poxvirus-associated infections share some clinical manifestations and exposure risks with anthrax, and so it is important to distinguish between the two. With this in mind, an archived collection of anthrax-negative DNA samples was retrospectively screened for poxviruses, and of the 148 human samples tested, 64 were positive. Sequence analysis confirmed the presence of orf virus, bovine papular stomatitis virus, and pseudocowpox virus. This study provides evidence of previously unrecognized poxvirus infections in Georgia and highlights the benefit of the timely identification of such infections by improving laboratory capacity.

Molecular phylogenetics of a recently isolated goat pox virus from Vietnam.

BACKGROUND: After a decade of silence, an outbreak of the contagious and Asian endemic disease, goat pox re-emerged in North Vietnam affecting more than 1800 heads with a mortality rate of 6.5%. The inevitable impact of goat pox on hide quality, breeding, chevon and milk production has resulted in a significant economic losses to the developing goat industry of Vietnam. In the act of establishing an effective control of this devastating disease, tracing the source of re-emergence via a phylogenetic study was carried out to reveal their genetic relatedness. Either skin scab or papule from the six affected provinces were collected, cultured into Vero cells followed by restricted enzyme digestion of targeted P32 gene DNA encoding. The P32 gene was then cloned and transformed into E.coli competent cells for further sequencing. RESULTS: The isolated sequence is deposited into GenBank under Accession No. MN317561/VNUAGTP1. The phylogenetic tree revealed high similarity of nucleotide and amino acid sequences to references goat pox strains accounting for 99.6 and 99.3, respectively. The Vietnamese strain is clustered together with currently circulating goat pox virus in China, India and Pakistan which suggested the origin of South China. CONCLUSIONS: This Vietnam isolate is clustered together with other Asian goat pox strains indicating the dissemination of a common goat pox virus within this continent.

Carp edema virus-related mortality in wild adult common carp (cyprinus carpio) in Italy.

Mortality in wild fish populations represents a challenging issue for public fish health inspectors. When a single fish species is involved, an infective aetiology is frequently suspected, with focus on viral notifiable diseases. However, other viral agents not subjected to regulation and causing mortality in common carp have been reported such as carp edema virus (CEV). In mid-June 2020, a severe common carp mortality was observed in an artificial lake in north-east of Italy. Sleepy fish were noted some days before the beginning of the mortality itself, which lasted several days and involved over 340 adult specimens. During the outbreak, water temperature was around 15°C, water quality was normal, and no adverse meteorological events were reported in the area. Four specimens, which showed severe cutaneous hyperaemia and increased mucus production on skin and gills, were tested by bacteriological methods and virological analysis targeting the main carp pathogens. Molecular analysis performed on gills, kidney and brains from all the fish analysed resulted positive for CEV, which, based on anamnestic information and laboratory findings, was considered the responsible for the mortality event herein described.

The Disease Ecology, Epidemiology, Clinical Manifestations, Management, Prevention, and Control of Increasing Human Infections with Animal Orthopoxviruses.

Zoonotic orthopoxvirus outbreaks have occurred repeatedly worldwide, including monkeypox in Africa and the United States, cowpox in Europe, camelpox in the Middle East and India, buffalopox in India, vaccinia in South America, and novel emerging orthopoxvirus infections in the United States, Europe, Asia, and South America. Waning smallpox immunity may increase the potential for animal-to-human transmission followed by further community transmission person-to-person (as demonstrated by monkeypox and buffalopox outbreaks) and by contact with fomites (as demonstrated by camelpox, cowpox, and, possibly, Alaskapox). The objectives of this review are to describe the disease ecology, epidemiology, clinical manifestations, prevention, and control of human infections with animal orthopoxviruses and to discuss the association with diminished population herd immunity formerly induced by vaccinia vaccination against smallpox. Internet search engines were queried with key words, and case reports, case series, seroprevalence studies, and epidemiologic investigations were found for review.