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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 -
Open Forum Infectious Diseases Apr 2024Though typically self-limiting, severe mpox infections have been treated with antiviral medications, most notably tecovirimat. Various reports exist of mpox progression...
Though typically self-limiting, severe mpox infections have been treated with antiviral medications, most notably tecovirimat. Various reports exist of mpox progression despite tecovirimat treatment. Treatment resistance can be due to acquired mpox strain mutations, most often occurring in an immunocompromised host. We present the case of a male with AIDS who developed disseminated treatment-resistant mpox infection complicated by superimposed bacterial and fungal infections. His orthopoxvirus polymerase chain reaction result remained positive despite treatment with 4 weeks of oral tecovirimat and 3 doses of intravenous cidofovir. Poor response to antiviral therapy was likely due to his underlying immunocompromised state; however, strain resistance cannot be ruled out given that the patient had started but not completed a 14-day course of tecovirimat 8 months prior, at the time of initial mpox diagnosis. Patients with mpox who are immunocompromised may require extended and additional treatment beyond the standard 14 days of tecovirimat, such as cidofovir, brincidofovir, or intravenous vaccina immune globulin.
PubMed: 38651138
DOI: 10.1093/ofid/ofae138 -
One Health (Amsterdam, Netherlands) Jun 2024The human population in Guyana, located on the South American continent, is vulnerable to zoonotic diseases due to an appreciable reliance on Neotropical wildlife as a...
BACKGROUND
The human population in Guyana, located on the South American continent, is vulnerable to zoonotic diseases due to an appreciable reliance on Neotropical wildlife as a food source and for trade. An existing suboptimal health surveillance system may affect the effective monitoring of important zoonotic diseases. To effectively address this deficit, a One Health zoonotic disease prioritization workshop was conducted to identify nationally significant zoonoses.
METHODS
Prioritization of zoonotic diseases was conducted for the first time in Guyana & Caribbean region using literature review, prioritization criteria and a risk prioritization tool in combination with a consultative One Health workshop. This involved multisectoral experts from varied disciplines of social, human, animal, and environmental health to prioritize zoonotic diseases using a modified semi-quantitative One Health Zoonotic Disease Prioritization (OHZDP) tool. The inclusion and exclusion criteria were applied to pathogen hazards in existence among wildlife in Guyana during the hazard identification phase.
RESULTS
In total, fifty zoonoses were chosen for prioritization. Based on their weighted score, prioritized diseases were ranked in order of relative importance using a one-to-five selection scale. In Guyana, this zoonotic disease prioritization method is the first significant step toward bringing together specialists from the fields of human, animal, and environmental health. Following discussion of the OHZDP Tool output among disease experts, a final zoonotic disease list, including tuberculosis, leptospirosis, gastroenteritis, rabies, coronavirus, orthopoxvirus, viral hemorrhagic fevers, and hepatitis were identified as the top eight priority zoonoses in Guyana.
CONCLUSIONS
This represents the first prioritization of nationally significant zoonotic diseases in Guyana and the English-speaking Caribbean. This One Health strategy to prioritize these eight zoonoses of wildlife origin is a step that will support future tracking and monitoring for disease prevalence among humans and wildlife and can be used as a decision-making guide for policymakers and stakeholders in Guyana.
PubMed: 38644970
DOI: 10.1016/j.onehlt.2024.100730 -
European Journal of Medicinal Chemistry May 2024New acyclic pyrimidine nucleoside phosphonate prodrugs with a 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid skeleton (O-DAPy nucleobase) were prepared...
Synthesis of LAVR-289, a new [(Z)-3-(acetoxymethyl)-4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid prodrug with pronounced antiviral activity against DNA viruses.
New acyclic pyrimidine nucleoside phosphonate prodrugs with a 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid skeleton (O-DAPy nucleobase) were prepared through a convergent synthesis by olefin cross-metathesis as the key step. Several acyclic nucleoside 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid prodrug exhibited in vitro antiviral activity in submicromolar or nanomolar range against varicella zoster virus (VZV), human cytomegalovirus (HCMV), human herpes virus type 1 (HSV-1) and type 2 (HSV-2), and vaccinia virus (VV), with good selective index (SI). Among them, the analogue 9c (LAVR-289) proved markedly inhibitory against VZV wild-type (TK+) (EC 0.0035 μM, SI 740) and for thymidine kinase VZV deficient strains (EC 0.018 μM, SI 145), with a low morphological toxicity in cell culture at 100 μM and acceptable cytostatic activity resulting in excellent selectivity. Compound 9c exhibited antiviral activity against HCMV (EC 0.021 μM) and VV (EC 0.050 μM), as well as against HSV-1 (TK-) (EC 0.0085 μM). Finally, LAVR-289 (9c) deserves further (pre)clinical investigations as a potent candidate broad-spectrum anti-herpesvirus drug.
Topics: Antiviral Agents; Prodrugs; Humans; DNA Viruses; Microbial Sensitivity Tests; Structure-Activity Relationship; Herpesvirus 1, Human; Molecular Structure; Herpesvirus 3, Human; Organophosphonates; Cytomegalovirus; Dose-Response Relationship, Drug; Vaccinia virus; Herpesvirus 2, Human
PubMed: 38643669
DOI: 10.1016/j.ejmech.2024.116412 -
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 -
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 -
Frontiers in Immunology 2024Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and...
Whole genome sequencing of recombinant viruses obtained from co-infection and superinfection of Vero cells with modified vaccinia virus ankara vectored influenza vaccine and a naturally occurring cowpox virus.
Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and animals. However, one biosafety concern about the use of MVA vectored vaccine is the potential for MVA to recombine with naturally occurring orthopoxviruses in cells and hosts in which it multiplies poorly and, therefore, producing viruses with mosaic genomes with altered genetic and phenotypic properties. We previously conducted co-infection and superinfection experiments with MVA vectored influenza vaccine (MVA-HANP) and a feline Cowpox virus (CPXV-No-F1) in Vero cells (that were semi-permissive to MVA infection) and showed that recombination occurred in both co-infected and superinfected cells. In this study, we selected the putative recombinant viruses and performed genomic characterization of these viruses. Some putative recombinant viruses displayed plaque morphology distinct of that of the parental viruses. Our analysis demonstrated that they had mosaic genomes of different lengths. The recombinant viruses, with a genome more similar to MVA-HANP (>50%), rescued deleted and/or fragmented genes in MVA and gained new host ranges genes. Our analysis also revealed that some MVA-HANP contained a partially deleted transgene expression cassette and one recombinant virus contained part of the transgene expression cassette similar to that incomplete MVA-HANP. The recombination in co-infected and superinfected Vero cells resulted in recombinant viruses with unpredictable biological and genetic properties as well as recovery of delete/fragmented genes in MVA and transfer of the transgene into replication competent CPXV. These results are relevant to hazard characterization and risk assessment of MVA vectored biologicals.
Topics: Chlorocebus aethiops; Animals; Cats; Humans; Influenza Vaccines; Cowpox virus; Vero Cells; Coinfection; Superinfection; Vaccinia virus; Vaccines, Synthetic; Whole Genome Sequencing
PubMed: 38633245
DOI: 10.3389/fimmu.2024.1277447