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Viruses Apr 2024To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific...
AIMS
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Topics: Humans; Antibodies, Viral; Smallpox Vaccine; B-Lymphocytes; Antibodies, Neutralizing; Cross Reactions; Vaccinia virus; Middle Aged; Immunologic Memory; Neutralization Tests; Smallpox; Animals; Male; T-Lymphocytes; Female; Enzyme-Linked Immunosorbent Assay; Orthopoxvirus; Vaccination; Chlorocebus aethiops; Adult; Lymphocyte Activation; Vero Cells
PubMed: 38675961
DOI: 10.3390/v16040620 -
Viruses Apr 2024Lumpy skin disease virus (LSDV) is a member of the capripoxvirus (CPPV) genus of the family. LSDV is a rapidly emerging, high-consequence pathogen of cattle, recently...
Lumpy skin disease virus (LSDV) is a member of the capripoxvirus (CPPV) genus of the family. LSDV is a rapidly emerging, high-consequence pathogen of cattle, recently spreading from Africa and the Middle East into Europe and Asia. We have sequenced the whole genome of historical LSDV isolates from the Pirbright Institute virus archive, and field isolates from recent disease outbreaks in Sri Lanka, Mongolia, Nigeria and Ethiopia. These genome sequences were compared to published genomes and classified into different subgroups. Two subgroups contained vaccine or vaccine-like samples ("Neethling-like" clade 1.1 and "Kenya-like" subgroup, clade 1.2.2). One subgroup was associated with outbreaks of LSD in the Middle East/Europe (clade 1.2.1) and a previously unreported subgroup originated from cases of LSD in west and central Africa (clade 1.2.3). Isolates were also identified that contained a mix of genes from both wildtype and vaccine samples (vaccine-like recombinants, grouped in clade 2). Whole genome sequencing and analysis of LSDV strains isolated from different regions of Africa, Europe and Asia have provided new knowledge of the drivers of LSDV emergence, and will inform future disease control strategies.
Topics: Lumpy skin disease virus; Animals; Genome, Viral; Lumpy Skin Disease; Phylogeny; Whole Genome Sequencing; Cattle; Africa, Central; Africa, Western; Disease Outbreaks
PubMed: 38675899
DOI: 10.3390/v16040557 -
Euro Surveillance : Bulletin Europeen... Apr 2024BackgroundFollowing the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future...
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.
Topics: Humans; Male; Netherlands; Seroepidemiologic Studies; Cross-Sectional Studies; Disease Outbreaks; Homosexuality, Male; Adult; Middle Aged; Vaccinia; Antibodies, Viral; Vaccination; Young Adult; Models, Theoretical; Enzyme-Linked Immunosorbent Assay; Immunoglobulin G
PubMed: 38666400
DOI: 10.2807/1560-7917.ES.2024.29.17.2300532 -
International Journal of Paleopathology Jun 2024This project seeks to create a differential diagnosis for lesions found on the skeletal remains of two children as a means to explore the presence of viral disease in...
OBJECTIVE
This project seeks to create a differential diagnosis for lesions found on the skeletal remains of two children as a means to explore the presence of viral disease in 16th- century Peru.
MATERIALS
Extremely well-preserved human remains of two children who died between the ages of 1-2 years old, recovered from the circum-contact (∼1540 CE) cemetery in Huanchaco, Peru.
METHODS
Macroscopic and radiographic analysis.
RESULTS
Both individuals present with cortical thickening, symmetrical destructive lesions, metaphyseal expansion, perforations, exposure of the medullary cavity, resorption of metaphyseal ends and necrosis of the long bones, and deposited reactive new bone. These features are consistent with osteomyelitis variolosa and bacterial osteomyelitis.
CONCLUSIONS
Three features of Individuals IG-124 and IG-493 suggest a highly consistent diagnosis of osteomyelitis variolosa: multiple skeletal lesions, the historical context of the area, and the high mortality rate of non-adults in the circum-contact cemetery.
SIGNIFICANCE
Although viral infections are ubiquitous and well documented historically, their etiologies are often difficult to determine in archaeological populations. Orthopoxvirus variola (smallpox) is one of the many viruses whose archaeological impact is still under explored in skeletal remains.
LIMITATIONS
The absence of smallpox in other children from the Huanchaco cemetery creates difficulty in ascertaining true prevalence rates or information on potential outbreaks.
SUGGESTIONS FOR FURTHER RESEARCH
Further research analyzing aDNA from calculus and/or residues using a DIP-GC-MS method might create a better understanding of how smallpox spread through the region.
Topics: Humans; Smallpox; Peru; History, 16th Century; Infant; Child, Preschool; Male; Osteomyelitis; Paleopathology; Female; Cemeteries
PubMed: 38653101
DOI: 10.1016/j.ijpp.2024.04.002 -
Acta Dermato-venereologica Apr 2024The association between molluscum contagiosum and concomitant atopic dermatitis and its impact on clinical features and treatment outcomes remains unclear. This...
The association between molluscum contagiosum and concomitant atopic dermatitis and its impact on clinical features and treatment outcomes remains unclear. This retrospective study, conducted in the paediatric dermatology clinic of a tertiary medical centre, aimed to compare molluscum patients with and without atopic dermatitis. A total of 615 children with molluscum were included, 13.17% of whom had atopic dermatitis. While the latter group exhibited higher lesion count and itchiness (p=0.026 and p=0.044, respectively), no significant differences were observed in average lesion diameter, ulceration, purulence, and erythema (p=0.239, p=0.730, p=0.682, and p=0.296, respectively). Both groups showed comparable responses to molluscum-specific and supportive treatments, with no distinct difference in outcomes or recurrence of visits. It was concluded that atopic dermatitis does not exacerbate molluscum morbidity, inflammation markers, treatment outcomes or recurrence rates.
Topics: Child; Humans; Molluscum Contagiosum; Dermatitis, Atopic; Retrospective Studies; Inflammation
PubMed: 38643362
DOI: 10.2340/actadv.v104.39983 -
Swiss Medical Weekly Mar 2024The COVID-19 pandemic has drawn attention to the benefit of wastewater-based epidemiology, particularly when case numbers are underreported. Underreporting may be an... (Observational Study)
Observational Study
AIM OF THE STUDY
The COVID-19 pandemic has drawn attention to the benefit of wastewater-based epidemiology, particularly when case numbers are underreported. Underreporting may be an issue with mpox, where biological reasons and stigma may prevent patients from getting tested. Therefore, we aimed to assess the validity of wastewater surveillance for monitoring mpox virus DNA in wastewater of a Central European city and its association with official case numbers.
METHODS
Wastewater samples were collected between 1 July and 28 August 2022 in the catchment area of Basel, Switzerland, and the number of mpox virus genome copies they contained was determined by real-time quantitative PCR. Logistic regression analyses were used to determine the odds of detectability of mpox virus DNA in wastewater, categorised as detectable or undetectable. Mann-Whitney U tests were used to determine associations between samples that tested positive for the mpox virus and officially reported cases and patients' recorded symptomatic phases.
RESULTS
Mpox virus DNA was detected in 15 of 39 wastewater samples. The number of positive wastewater samples was associated with the number of symptomatic cases (odds ratio [OR] = 2.18, 95% confidence interval (CI) = 1.38-3.43, p = 0.001). The number of symptomatic cases differed significantly between days with positive versus negative wastewater results (median = 11 and 8, respectively, p = 0.0024).
CONCLUSION
Mpox virus DNA was detectable in wastewater, even when officially reported case numbers were low (0-3 newly reported mpox cases corresponding to 6-12 symptomatic patients). Detectability in wastewater was significantly associated with the number of symptomatic patients within the catchment area. These findings illustrate the value of wastewater-based surveillance systems when assessing the prevalence of emerging and circulating infectious diseases.
Topics: Humans; Wastewater; Monkeypox virus; Switzerland; Mpox (monkeypox); Pandemics; Wastewater-Based Epidemiological Monitoring; DNA
PubMed: 38642339
DOI: 10.57187/s.3706 -
Journal of Clinical Microbiology May 2024The mpox outbreak, caused by monkeypox virus (MPXV), accelerated the development of molecular diagnostics. In this study, we detail the evaluation of the Research Use...
UNLABELLED
The mpox outbreak, caused by monkeypox virus (MPXV), accelerated the development of molecular diagnostics. In this study, we detail the evaluation of the Research Use Only (RUO) NeuMoDx MPXV assay by multiple European and US sites. The assay was designed and developed by Qiagen for the NeuMoDx Molecular Systems. Primers and probes were tested for specificity and inclusivity . The analytical sensitivity of the assay was determined by testing dilutions of synthetic and genomic MPXV DNA. A total of 296 clinical samples were tested by three sites; the Johns Hopkins University (US), UZ Gent (Belgium, Europe), and Hospital Universitario San Cecilio (Spain, Europe). The analytical sensitivity of the assay was 50 copies/mL for both clades I and II. The assay showed 100% identity for 80 clade I and 99.98% identity for 5,162 clade II genomes. Clade II primers and probes showed 100% specificity; however, identity of at least one of the two sets of clade I primers and probes with variola, cowpox, camelpox, and vaccinia viruses was noticed. The clinical validation showed sensitivity of 99.21% [95% confidence interval (CI): 95.66-99.98%] and specificity of 96.64% (95% CI: 91.62-99.08%) for lesion swab samples. The NeuMoDx MPXV Test shows acceptable analytical and clinical performance. The assay improves the laboratory's workflow as it consolidates nucleic acid extraction, PCR, data analysis, and interpretation and can be interfaced. The Test Strip can differentiate clades I and II, which has important laboratory safety implications.
IMPORTANCE
In this manuscript, we provide detailed analysis and clinical evaluation of the assay using a large cohort of clinical samples across three academic centers in Europe and the United States. Because the assay differentiates MPXV clades I and II, this manuscript is timely due to the current need to rule out the regulated clade I by diagnostic clinical laboratories. In December 2023, and due to first report of cases of sexually transmitted clade I infections in the Democratic Republic of the Congo, when generic assays that do not differentiate the clades are used, samples are considered regulated. The assay meets the need of full automation and has a marked positive impact on the laboratory workflow.
Topics: Humans; Sensitivity and Specificity; Monkeypox virus; Real-Time Polymerase Chain Reaction; Mpox (monkeypox); Molecular Diagnostic Techniques; Europe; United States; Automation, Laboratory; DNA Primers; Belgium
PubMed: 38639489
DOI: 10.1128/jcm.00028-24 -
Human Vaccines & Immunotherapeutics Dec 2024The growing number of Mpox cases in China has posed a challenge to public health. The prevalence of men who have sex with men behaviors among students has been...
The growing number of Mpox cases in China has posed a challenge to public health. The prevalence of men who have sex with men behaviors among students has been consistently increasing each year in China, accompanied by a high frequency of unprotected anal sex. As crowded places, schools are highly likely to cause an Mpox outbreak among students through long-term close contact. Understanding university students' perceptions about Mpox and willingness to vaccinate play a vital role in implementing preventive measures in schools. This study aimed to assess knowledge, concerns, and vaccine acceptance toward Mpox among university students in North and Northeast China. A cross-sectional study was conducted among 3831 university students from seven universities in North and Northeast China between September 10 and September 25, 2023. This study found a relative insufficiency in Mpox knowledge among university students (71.60%), with less than half expressing concern about the Mpox outbreak (39.57%), and the majority exhibiting a positive attitude to vaccination (76.30%). Multivariate regression analysis revealed that a good knowledge level was associated with age, study discipline, education level, and a high level of concern about Mpox. Male, elderly, or highly educated participants had a low level of concern about Mpox. Participants with a high level of knowledge toward Mpox were more likely to have the vaccination willingness. This study might help governments and schools to understand students' Mpox perceptions and vaccination intentions, enabling them to implement effective measures in addressing the issue of inadequate understanding regarding Mpox among university students.
Topics: Aged; Humans; Male; Female; Cross-Sectional Studies; Mpox (monkeypox); Homosexuality, Male; Universities; Sexual and Gender Minorities; Vaccines; China
PubMed: 38639480
DOI: 10.1080/21645515.2024.2339922 -
Euro Surveillance : Bulletin Europeen... Apr 2024BackgroundMpox, caused by monkeypox virus (MPXV), was considered a rare zoonotic disease before May 2022, when a global epidemic of cases in non-endemic countries led to...
BackgroundMpox, caused by monkeypox virus (MPXV), was considered a rare zoonotic disease before May 2022, when a global epidemic of cases in non-endemic countries led to the declaration of a Public Health Emergency of International Concern. Cases of mpox in Ireland, a country without previous mpox reports, could reflect extended local transmission or multiple epidemiological introductions.AimTo elucidate the origins and molecular characteristics of MPXV circulating in Ireland between May 2022 and October 2023.MethodsWhole genome sequencing of MPXV from 75% of all Irish mpox cases (182/242) was performed and compared to sequences retrieved from public databases (n = 3,362). Bayesian approaches were used to infer divergence time between sequences from different subclades and evaluate putative importation events from other countries.ResultsOf 242 detected mpox cases, 99% were males (median age: 35 years; range: 15-60). All 182 analysed genomes were assigned to Clade IIb and, presence of 12 distinguishable subclades suggests multiple introductions into Ireland. Estimation of time to divergence of subclades further supports the hypothesis for multiple importation events from numerous countries, indicative of extended and sustained international spread of mpox. Further analysis of sequences revealed that 92% of nucleotide mutations were from cytosine to thymine (or from guanine to adenine), leading to a high number of non-synonymous mutations across subclades; mutations associated with tecovirimat resistance were not observed.ConclusionWe provide insights into the international transmission dynamics supporting multiple introductions of MPXV into Ireland. Such information supported the implementation of evidence-informed public health control measures.
Topics: Male; Humans; Adult; Female; Ireland; Monkeypox virus; Bayes Theorem; Mpox (monkeypox); Disease Outbreaks
PubMed: 38639093
DOI: 10.2807/1560-7917.ES.2024.29.16.2300505 -
Nature Communications Apr 2024The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person...
The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.
Topics: Humans; Monkeypox virus; Genomics; Orthopoxvirus; Mpox (monkeypox); Poxviridae
PubMed: 38637500
DOI: 10.1038/s41467-024-46949-7