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Reports of mpox are rising in Africa where the disease is endemic and in new countries where the disease has not been previously seen. The 2022 global outbreak of clade II mpox and an ongoing outbreak of the more lethal clade I mpox highlight the pandemic potential for monkeypox virus. Waning population immunity after the cessation of routine immunization for smallpox plays a key role in the changing epidemiologic patterns of mpox. Sustained human-to-human transmission of mpox is occurring widely in the context of insufficient population immunity, fueling genetic mutations that affect the accuracy of some diagnostic tests and that could lead to changing virulence. Additional research should address complex challenges for control of mpox, including improved diagnostics and medical countermeasures. The availability of vaccines should be expanded not only for outbreak response but also for broader routine use for persons in mpox-endemic countries.

We report 2 immunocompetent and otherwise healthy adults in the United States who had monkeypox and required hospitalization for viral myocarditis. Both patients were unvaccinated against orthopoxviruses. They had shortness of breath or chest pain and elevated cardiac biomarkers. No immediate complications were observed. They were discharged home after symptoms resolved.

The 2022 Monkeypox virus (MPXV) global outbreak boosted development of multiple serological assays to aid understanding of Mpox immunology. The study aimed to assess a multiplexed solid-phase electrochemiluminescence immunoassay (Meso Scale Discovery (MSD)) for simultaneous detection of antibodies against MPXV, including A35, E8 and M1 antigens, along with corresponding Vaccina Virus (VACV) homologues and demonstrate its accuracy in assessing antibody titres post-vaccination and infection. Assay performance was assessed for simultaneous detection of antibodies against MPXV and corresponding VACV antigens. Sensitivity and specificity were evaluated with paediatric negatives (n = 215), pre- and post-IMVANEX vaccinated (n = 80), and MPXV (Clade IIb, n = 39) infected serum samples. The assay demonstrated high specificity (75.68 % (CI: 69.01–81.29) - 95.98 % (CI:92.54–97.87)) and sensitivity (62.11 % (CI:52.06–71.21) - 98.59 % (CI:92.44 %–99.93 %)) depending on the Orthopoxvirus antigen. Preferential binding was observed between MPXV-infected individuals and MPXV antigens, while vaccinated individuals exhibited increased binding to VACV antigens. These results highlight differential binding patterns between antigen homologues in related viruses. Overall, this assay demonstrates high sensitivities in detecting antibodies for multiple relevant MPXV and VACV antigens post-infection and post-vaccination, indicating its utility in understanding immune responses to Orthopoxviruses in current and future outbreaks and evaluating the immunogenicity of new-generation Mpox-specific vaccinations. •Simultaneous measurement of IgG to multiple MPXV and VACV homologous proteins•Sensitive and specific assay for detecting Orthopoxvirus antibodies•Detects Orthopoxvirus IgG antibodies in vaccinated sera 220 days after two doses•Mpox-infected individuals show preferential binding to MPXV over VACV antigens•Higher anti-MPXV A29 and anti-VACV A27 IgG titres post infection versus vaccination

Since the eradication of smallpox, there have been increases in poxvirus infections and the emergence of several novel poxviruses that can infect humans and domestic animals. In 2015, a novel poxvirus was isolated from a resident of Alaska. Diagnostic testing and limited sequence analysis suggested this isolate was a member of the Orthopoxvirus (OPXV) genus but was highly diverged from currently known species, including Akhmeta virus. Here, we present the complete 210,797 bp genome sequence of the Alaska poxvirus isolate, containing 206 predicted open reading frames. Phylogenetic analysis of the conserved central region of the genome suggested the Alaska isolate shares a common ancestor with Old World OPXVs and is diverged from New World OPXVs. We propose this isolate as a member of a new OPXV species, Alaskapox virus (AKPV). The AKPV genome contained host range and virulence genes typical of OPXVs but lacked homologs of C4L and B7R, and the hemagglutinin gene contained a unique 120 amino acid insertion. Seven predicted AKPV proteins were most similar to proteins in non-OPXV Murmansk or NY_014 poxviruses. Genomic analysis revealed evidence suggestive of recombination with Ectromelia virus in two putative regions that contain seven predicted coding sequences, including the A-type inclusion protein.

•40 years after smallpox eradication, monkeypox is a human disease.•2018–19 export of monkeypox from Nigeria to the UK, Israel and Singapore.•Monkeypox epidemiology needs more study.•Human monkeypox, an unintended consequence of smallpox eradication.•Other orthopox viruses, a threat to animal and human health. Smallpox eradication, coordinated by the WHO and certified 40 years ago, led to the cessation of routine smallpox vaccination in most countries. It is estimated that over 70% of the world’s population is no longer protected against smallpox, and through cross-immunity, to closely related orthopox viruses such as monkeypox. Monkeypox is now a re-emerging disease. Monkeypox is endemic in as yet unconfirmed animal reservoirs in sub-Saharan Africa, while its human epidemiology appears to be changing. Monkeypox in small animals imported from Ghana as exotic pets was at the origin of an outbreak of human monkeypox in the USA in 2003. Travellers infected in Nigeria were at the origin of monkeypox cases in the UK in 2018 and 2019, Israel in 2018 and Singapore in2019. Together with sporadic reports of human infections with other orthopox viruses, these facts invite speculation that emergent or re-emergent human monkeypox might fill the epidemiological niche vacated by smallpox. An ad-hoc and unofficial group of interested experts met to consider these issues at Chatham House, London in June 2019, in order to review available data and identify monkeypox-related research gaps. Gaps identified by the experts included:•understanding of zoonotic hosts, reservoirs and vectors.•risks associated with transmission.•full description of the clinical spectrum and the natural history of infection including an estimation of the prevalence of monkeypox specific antibodies in humans living in areas of emergence.The experts further agreed on the need for a better understanding of the genomic evolution and changing epidemiology of orthopox viruses, the usefulness of in-field genomic diagnostics, and the best disease control strategies, including the possibility of vaccination with new generation non-replicating smallpox vaccines and treatment with recently developed antivirals.

Monkeypox virus (MPXV) has emerged as a threatening zoonosis. Its spread around the world has been growing fast over the last 2 years, particularly in 2022. The reasons for this sudden spread are probably multifactorial. The R0 values of the two MPXV clades are rather low, and a massive pandemic is considered unlikely, although the increase in the number of single-nucleotide polymorphisms found in the 2022 MPXV strain could indicate an accelerated human adaptation. Very little is known about the risks of an infection during pregnancy for both the mother and the fetus. Further observations must be made to create clear, adapted, evidence-based guidelines. This article summarizes the current knowledge about MPXV infections and similar pregnancy virus infections.

Human mpox is a zoonotic disease, caused by the mpox virus (MPXV), that can spread either between animals and humans or humans and humans. In 1970 the first human case of mpox was reported in Zaire, Democratic Republic of the Congo (DRC). Other notable human mpox outbreaks in non-endemic countries were identified in June 2003 in the United States, in July 2021 in Dallas (USA), and the most recent one in May 2022 in Europe in the United Kingdom (UK). During the 2022 outbreak, sexual intercourse was observed to be the most prevalent transmission method, although other means should not be ignored, such as the involvement of respiratory droplets, exposure to surfaces and skin suspected of contamination. In the context of the current mpox outbreak, we consider it important and necessary to correctly identify the virus, use the proper laboratory testing for a correct diagnosis of mpox, understand the means of prophylaxis, and apply the correct treatment, highlighting these facts being the aim of this study.

Abstract Mpox has recently re-emerged as a global entity of concern. We report one of the first pediatric cases in the United States and provide updated recommendations relevant to infection control and prevention measures of those in close contact with mpox.

In west and central Africa, monkeypox occurs mainly in older children, adolescents and young adults. In two large epidemiology studies of monkeypox outbreaks, the investigators observed a sizable number of coinfections of chickenpox (varicella) and monkeypox. Based on a review of the literature, we propose that chickenpox (human herpesvirus-3 infection) is a risk factor for acquisition of monkeypox infection. Our hypothesis states that the chickenpox skin lesion provides an entry site for the monkeypox virus, which is harbored on a fomite in the environment of the patient. The fact that monkeypox can enter via a scratch or abrasion is a known mechanism of spread for three other poxviruses, including mousepox (ectromelia), orf and molluscum contagiosum. There are many similarities in pathogenesis between certain poxviruses and chickenpox, including a viremia with a cellular stress response leading to high levels of the IL-6 cytokine. One very revealing observation in the two epidemiology studies was that the number of pox as well as the severity of disease in children with chickenpox and monkeypox coinfection was not greater than found in children with monkeypox alone. Based on the above observations, we conclude that, when chickenpox precedes monkeypox, priming of the immune system by the earlier chickenpox infection moderates the severity of the secondary infection with monkeypox. This conclusion also has important public health implications about chickenpox surveillance.

In the late 1970s, global vaccination programs resulted in the eradication of smallpox. The Monkeypox virus (MPXV), which is closely related to the smallpox-inducing variola virus, was previously endemic only in Sub-Saharan Africa but is currently spreading worldwide. Only older people who have been vaccinated against smallpox are expected to be sufficiently protected against poxviruses. Here I will summarize current knowledge about the virus, the disease caused by MPXV infections, and strategies to limit its spread.