Variability in clinical assessment of clade IIb mpox lesions
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PROVIDER: S-EPMC10914632 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
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Project description:Mpox is a great public health concern worldwide currently; thus, a global primary epidemiological analysis of mpox and a phylogenetic analysis of currently circulating MPXV strains based on open-source data is necessary. A total of 83,419 confirmed cases with 72 deaths were reported from 7 May to 23 December 2022, representing an ongoing increasing trend. Mpox was largely restricted to being endemic in children in West Africa (WA) before 2022, and it mainly spread from animals to humans. Our analysis highlights that mpox has not only spread across regions within Africa but has also led to most infection events outside Africa. Currently, mpox has been dominated by human-to-human spread in 110 countries, with the majority of cases distributed in the non-endemic regions of Europe and North America. These data indicate that the geographic range, transmission route, vulnerable populations, and clinical manifestations of mpox have changed, which suggests that the niche of mpox has the potential to change. Remarkably, approximately 38,025 suspected mpox cases were recorded in West and Central Africa during 1970-2022, which implied that the epidemiology of mpox in the two regions remained cryptic, suggesting that strengthening the accuracy of molecular diagnosis on this continent is a priority. Moreover, 617 mpox genomes have been obtained from 12 different hosts; these data imply that the high host diversity may contribute to its ongoing circulation and global outbreak. Furthermore, a phylogenetic analysis of 175 MPXV genome sequences from 38 countries (regions) showed that the current global mpox outbreak was caused by multiple sub-clades in the clade IIb lineage. These data suggest that MPXV strains from the clade IIb lineage may play a predominated role in the spread of mpox worldwide, implying that the current mpox outbreak has a single infection source. However, further investigations into the origin of the new global mpox outbreak are necessary. Therefore, our analysis highlights that adjusted timely interventive measures and surveillance programs, especially using cheap and quick strategies such as wastewater monitoring the DNA of MPXV in Africa (WA), are important for uncovering this disease's transmission source and chain, which will help curb its further spread.
| S-EPMC9966881 | biostudies-literature
Project description:Generating an infectious non-human primate (NHP) model using a prevalent monkeypox virus (MPXV) strain has emerged as a crucial strategy for assessing the efficacy of vaccines and antiviral drugs against human MPXV infection. Here, we established an animal model by infecting cynomolgus macaques with the prevalent MPXV strain, WIBP-MPXV-001, and simulating its natural routes of infection. A comprehensive analysis and evaluation were conducted on three animals, including monitoring clinical symptoms, collecting hematology data, measuring viral loads, evaluating cellular and humoral immune responses, and examining histopathology. Our findings revealed that initial skin lesions appeared at the inoculation sites and subsequently spread to the limbs and back, and all infected animals exhibited bilateral inguinal lymphadenopathy, eventually leading to a self-limiting disease course. Viral DNA was detected in post-infection blood, nasal, throat, rectal and blister fluid swabs. These observations indicate that the NHP model accurately reflects critical clinical features observed in human MPXV infection. Notably, the animals displayed clinical symptoms and disease progression similar to those of humans, rather than a lethal outcome as observed in previous studies. Historically, MPXV was utilized as a surrogate model for smallpox. However, our study contributes to a better understanding of the dynamics of current MPXV infections while providing a potential infectious NHP model for further evaluation of vaccines and antiviral drugs against mpox infection. Furthermore, the challenge model closely mimics the primary natural routes of transmission for human MPXV infections. This approach enhances our understanding of the precise mechanisms underlying the interhuman transmission of MPXV.
| S-EPMC10984234 | biostudies-literature
Project description:Monkeypox is caused by a sylvatic, double-stranded DNA zoonotic virus. Since 1 January 2022, monkeypox cases have been reported to WHO from 106 Member States across six WHO regions, and as of 2 October 2022, a total of 68,900 confirmed cases, including 25 deaths, occurred. Here, by using a whole genome approach, we perform a genetic and phylodynamic survey of the monkeypox virus Clade IIb B.1, which is the lineage causing the current multi-country outbreak. Results suggest that outbreaks seem to be isolated and localized in several epidemic clusters with geographic consistency. Currently, monkeypox appears to be a virus with a flattened genetic variability in terms of evolutionary path, with a very slow rate of growth in the population size. This scenario confirms that the monkeypox virus lacks the evolutionary advantage, given by the high level of mutation rate, which is very strong in RNA viruses. Of course, constant genome-based monitoring must be performed over time in order to detect the change in its genetic composition, if any.
| S-EPMC9695420 | biostudies-literature
Project description:Metagenomic sequencing of mpox virus clade Ib lesions
| PRJEB88042 | ENA
Project description:From 1 January 2022 to 31 May 2024, the World Health Organization (WHO) reported 97,745 laboratory-confirmed Mpox cases, including 203 deaths, across 116 countries. Despite a 2.3% decrease in new cases in May 2024 compared to April 2024, significant regional variations persist. The African Region reported the highest proportion of new cases, while other regions experienced mixed trends. Phylogenomic analyses of the Mpox virus Clade IIb lineage B.1 reveal stable genetic variability with minimal diversification. The Bayesian Skyline Plot indicates a generally stable viral population size with a modest peak in late 2023, followed by a decline. In general, the data indicate that the MPXV outbreak is primarily localized within a few consistent geographic clusters. The virus's evolution is relatively slow, as indicated by its stable genetic variability, and Clade IIb lineage B.1 does not currently show signs of rapid genetic changes or population growth. The current low level of genetic diversity should not lead to complacency. Ongoing genomic surveillance is essential for effective outbreak management and understanding. This monitoring is crucial for identifying any shifts in the virus's behavior or transmission, allowing for prompt public health responses and adjustments. In addition, continued vigilance is necessary to detect any new variants that might influence the outbreak's trajectory.
| S-EPMC11434445 | biostudies-literature
Project description:The 2022 monkeypox outbreak involved rapid global dissemination, prompting research into animal models for the monkeypox virus (MPXV), including non-human primates and mice. However, studies utilizing rabbits as models remain limited. In this study, we established three rabbit models using the current epidemic MPXV strain. Following intravenous MPXV injection, adult rabbits exhibited characteristic clinical manifestations, including widespread rash and fever, with viral replication in the skin, lungs, and testes, resulting in severe pathological damage by 6 days post-infection (dpi). Intradermal injection of MPXV into the dorsal skin of adult rabbits produced red lesions with central necrosis and hemorrhage accompanied by dense inflammatory infiltrates. Abundant viral particles were observed in epidermal cells at 6 dpi. Additionally, a fatal MPXV model was developed in 10-day-old rabbits using intranasal virus administration. These young rabbits exhibited lethargy and diarrhea beginning at 2 dpi, significant weight loss, and a 50% mortality rate by 15 dpi. Viral dissemination was detected in multiple organs, leading to extensive multi-organ damage. This study highlights the utility of rabbit models for MPXV, displaying typical clinical features and pathogenic mechanisms.
| S-EPMC11849023 | biostudies-literature
Project description:While mpox was well characterised during the 2022 global Clade IIb outbreak, little is known about persistent morbidity. We present interim results of a prospective cohort study of 95 mpox patients assessed 3-20 weeks post-symptom onset. Two-thirds of participants had residual morbidity, including 25 with persistent anorectal and 18 with genital symptoms. Loss of physical fitness, new-onset/worsened fatigue and mental health problems were reported in 36, 19 and 11 patients, respectively. These findings require attention by healthcare providers.
| S-EPMC9936596 | biostudies-literature
Project description:BackgroundDue to limited diagnostic capacity and availability of point-of-care tests, diagnosis of Clade I mpox in the geographical regions most affected is usually on clinical grounds. This may be complicated due to the similarity between mpox and varicella (chickenpox) lesions. Visual assessment of lesions is also used for determining clinical progress and to assess patient outcomes in clinical trials. However, there has been no investigation into whether clinicians can (i) identify Clade I mpox compared to other viral lesions (ii) differentiate between Clade I mpox lesion stages.Methodology/principle findingsThe objective of this study was to evaluate inter-rater reliability and agreement between clinicians assessing lesions in patients with Clade I mpox. We presented experienced clinicians with 17 images of Clade I mpox or varicella and asked them to independently indicate the most likely diagnosis-mpox or varicella-and to categorise the lesions according to their stage. When selecting the most likely diagnosis, accuracy varied across all images, the inter-rater reliability was poor (κ = 0.223; z = 10.1) and agreement was moderate (Po = 68%). When categorising lesions according to their type, if a single lesion type was present in the image, inter-rater reliability was moderate (κ = 0.671, z = 40.6) and agreement was good (Po = 78%), but when multiple lesion types were shown in an image, both inter-rater reliability (κ = 0.153, z = 10.5) and agreement (Po = 29%) decreased substantially.ConclusionsThis study demonstrates that there are presently limitations in using visual assessment to diagnose Clade I mpox and evaluate lesion stage and treatment outcomes, which have an impact on clinical practice, public health and clinical trials. More robust indicators and tools are required to inform clinical, public-health, and research priorities, but these must be implementable in countries affected by mpox.
| S-EPMC11226010 | biostudies-literature
Project description:Founder Effects, Gene Disruptions and Continuous non-Zoonotic Human Transmission of Monkeypox Virus from 18 Genomes Predating the 2022 Global Outbreak
| PRJNA864638 | ENA
Project description: Not available
| S-EPMC11646081 | biostudies-literature