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Geospatial Health Jun 2024Mpox is an emerging, infectious disease that has caused outbreaks in at least 91 countries from May to August 2022. We assessed the link between international air travel...
Mpox is an emerging, infectious disease that has caused outbreaks in at least 91 countries from May to August 2022. We assessed the link between international air travel patterns and Mpox transmission risk, and the relationship between the translocation of Mpox and human mobility dynamics after travel restrictions due to the COVID-19 pandemic had been lifted. Our three novel observations were that: i) more people traveled internationally after the removal of travel restrictions in the summer of 2022 compared to pre-pandemic levels; ii) countries with a high concentration of global air travel have the most recorded Mpox cases; and iii) Mpox transmission includes a number of previously nonendemic regions. These results suggest that international airports should be a primary location for monitoring the risk of emerging communicable diseases. Findings highlight the need for global collaboration concerning proactive measures emphasizing realtime surveillance.
Topics: Humans; Air Travel; COVID-19; SARS-CoV-2; Mpox (monkeypox); Global Health; Pandemics; Airports; Communicable Diseases, Emerging; Travel; Disease Outbreaks
PubMed: 38872388
DOI: 10.4081/gh.2024.1261 -
Nature Medicine Jun 2024Outbreaks of mpox have historically resulted from zoonotic spillover of clade I monkeypox virus (MPXV) in Central Africa and clade II MPXV in West Africa. In 2022,...
Outbreaks of mpox have historically resulted from zoonotic spillover of clade I monkeypox virus (MPXV) in Central Africa and clade II MPXV in West Africa. In 2022, subclade IIb caused a global epidemic linked to transmission through sexual contact. Here, we describe the epidemiological and genomic features of an mpox outbreak in a mining region in the Eastern Democratic Republic of the Congo (DRC), caused by clade I MPXV. Surveillance data collected between September 2023 and January 2024 identified 241 suspected cases. Genomic analysis demonstrates a distinct clade I lineage divergent from previously circulating strains in the DRC. Of the 108 PCR-confirmed mpox cases, the median age of individuals was 22 years, 51.9% were female, and 29% were sex workers, suggesting a potential role for sexual transmission. The predominance of APOBEC3-type mutations and the estimated emergence time around mid-September 2023 imply recent sustained human-to-human transmission.
PubMed: 38871006
DOI: 10.1038/s41591-024-03130-3 -
Cornea Jun 2024The objective of this study was to present a rare case of prolonged and severe ocular monkeypox virus infection in the absence of systemic manifestations.
PURPOSE
The objective of this study was to present a rare case of prolonged and severe ocular monkeypox virus infection in the absence of systemic manifestations.
METHODS
This was a single case report.
RESULTS
A 60-year-old man, having been symptomatic for 9 days, presented with several umbilicated, ulcerated papules on the left cheek, left side of the nose, and left upper eyelid, along with marked follicular conjunctivitis and multiple conjunctival ulcerations. Two weeks after presentation, he developed an irregular, 360° circumferential opacity in the peripheral cornea that progressed to a large epithelial defect with corneal thinning. Although the initial eyelid lesions and conjunctivitis quickly resolved, the patient experienced nonresolving corneal inflammation manifest with peripheral corneal thinning, epithelial defects, and stromal keratitis. Four months after presentation, with the presumptive diagnosis of peripheral ulcerative keratitis, the patient was treated with intravenous steroids and immunosuppressive treatment, after which the ocular surface inflammation improved. However, the inflammation recurred 12 weeks later, and the patient developed severe perilimbal necrotizing conjunctivitis, followed by recurrence of ulcerated nodular eyelid lesions. Eight months after presentation, nucleic acid amplification tests from eyelid lesion swabs returned positive for nonvariola Orthopoxviruses, which led to the diagnosis of mpox. Within 2 weeks of beginning antiviral treatment with systemic tecovirimat and cidofovir and topical trifluridine, the eyelid lesions, conjunctivitis, and corneal inflammation resolved.
CONCLUSIONS
We present an unusual and challenging case of ocular mpox with severe ocular surface inflammation including peripheral corneal thinning and epithelial defects, without systemic disease. Initiation of antiviral treatment resulted in a quick resolution of the ocular disease.
PubMed: 38870146
DOI: 10.1097/ICO.0000000000003574 -
Scientific Reports Jun 2024Since spring 2022, the global epidemiology of the monkeypox virus (MPXV) has changed. The unprecedented increase of human clade II MPXV cases worldwide heightened...
Since spring 2022, the global epidemiology of the monkeypox virus (MPXV) has changed. The unprecedented increase of human clade II MPXV cases worldwide heightened concerns about this emerging zoonotic disease. We analysed the positivity rates, viral loads, infectiousness, and persistence of MPXV DNA for up to 4 months in several biological samples from 89 MPXV-confirmed cases. Our data showed that viral loads and positivity rates were higher during the first two weeks of symptoms for all sample types. Amongst no-skin-samples, respiratory specimens showed higher MPXV DNA levels and median time until viral clearance, suggesting their usefulness in supporting MPXV diagnosis, investigating asymptomatic patients, and monitoring viral shedding. Infectious virus was cultured from respiratory samples, semen, and stools, with high viral loads and collected within the first 10 days. Notably, only one saliva and one semen were found positive for viral DNA after 71 and 31 days from symptoms, respectively. The focus on bloodstream samples showed the best testing sensitivity in plasma, reporting the overall highest MPXV DNA detection rate and viral loads during the 3-week follow-up as compared to serum and whole-blood. The data here presented can be useful for MPXV diagnostics and a better understanding of the potential alternative routes of its onward transmission.
Topics: Humans; DNA, Viral; Viral Load; Body Fluids; Male; Monkeypox virus; Kinetics; Semen; Mpox (monkeypox); Saliva; Female; Adult; Virus Shedding; Middle Aged
PubMed: 38866796
DOI: 10.1038/s41598-024-63044-5 -
American Journal of Kidney Diseases :... Jun 2024Monkeypox (mpox) is an orthopoxviral zoonotic disease with a similar, but less severe, clinical presentation as smallpox. However, immunocompromised patients such as...
Monkeypox (mpox) is an orthopoxviral zoonotic disease with a similar, but less severe, clinical presentation as smallpox. However, immunocompromised patients such as solid organ transplant recipients are at higher risk of developing severe forms of the disease. Herein, we describe the case of a 43 years-old female kidney transplant recipient that manifested severe skin ulcers alongside nodular lung opacities and pleural effusion attributed directly to the Monkeypox virus. Notwithstanding the initiation of early treatment with tecovirimat, a satisfactory response was not achieved until a reduction in immunosuppression to everolimus monotherapy, coupled with the transition to cidofovir for antiviral treatment. In conclusion, mpox has the potential to produce a severe form of systemic infection in individuals who have undergone solid organ transplantation, demanding a meticulous approach involving sequential antiviral treatment and modifications to immunosuppressive regimens in order to achieve complete healing.
PubMed: 38866126
DOI: 10.1053/j.ajkd.2024.06.001 -
Journal of Infection and Public Health Jul 2024Poxviruses comprise a group of large double-stranded DNA viruses and are known to cause diseases in humans, livestock animals, and other animal species. The Mpox virus...
Formulation of next-generation polyvalent vaccine candidates against three important poxviruses by targeting DNA-dependent RNA polymerase using an integrated immunoinformatics and molecular modeling approach.
BACKGROUND
Poxviruses comprise a group of large double-stranded DNA viruses and are known to cause diseases in humans, livestock animals, and other animal species. The Mpox virus (MPXV; formerly Monkeypox), variola virus (VARV), and volepox virus (VPXV) are among the prevalent poxviruses of the Orthopoxviridae genera. The ongoing Mpox infectious disease pandemic caused by the Mpox virus has had a major impact on public health across the globe. To date, only limited repurposed antivirals and vaccines are available for the effective treatment of Mpox and other poxviruses that cause contagious diseases.
METHODS
The present study was conducted with the primary goal of formulating multi-epitope vaccines against three evolutionary closed poxviruses i.e., MPXV, VARV, and VPXV using an integrated immunoinformatics and molecular modeling approach. DNA-dependent RNA polymerase (DdRp), a potential vaccine target of poxviruses, has been used to determine immunodominant B and T-cell epitopes followed by interactions analysis with Toll-like receptor 2 at the atomic level.
RESULTS
Three multi-epitope vaccine constructs, namely DdRp_MPXV (V1), DdRp_VARV (V2), and DdRp_VPXV (V3) were designed. These vaccine constructs were found to be antigenic, non-allergenic, non-toxic, and soluble with desired physicochemical properties. Protein-protein docking and interaction profiling analysis depicts a strong binding pattern between the targeted immune receptor TLR2 and the structural models of the designed vaccine constructs, and manifested a number of biochemical bonds (hydrogen bonds, salt bridges, and non-bonded contacts). State-of-the-art all-atoms molecular dynamics simulations revealed highly stable interactions of vaccine constructs with TLR2 at the atomic level throughout the simulations on 300 nanoseconds. Additionally, the outcome of the immune simulation analysis suggested that designed vaccines have the potential to induce protective immunity against targeted poxviruses.
CONCLUSIONS
Taken together, formulated next-generation polyvalent vaccines were found to have good efficacy against closely related poxviruses (MPXV, VARV, and VPXV) as demonstrated by our extensive immunoinformatics and molecular modeling evaluations; however, further experimental investigations are still needed.
Topics: Viral Vaccines; Poxviridae; Computational Biology; Epitopes, T-Lymphocyte; DNA-Directed RNA Polymerases; Models, Molecular; Animals; Humans; Poxviridae Infections; Epitopes, B-Lymphocyte; Molecular Docking Simulation; Immunoinformatics
PubMed: 38865776
DOI: 10.1016/j.jiph.2024.102470 -
Frontiers in Cellular and Infection... 2024Monkeypox (mpox) is an infectious disease caused by the mpox virus and can potentially lead to fatal outcomes. It resembles infections caused by viruses from other... (Review)
Review
Monkeypox (mpox) is an infectious disease caused by the mpox virus and can potentially lead to fatal outcomes. It resembles infections caused by viruses from other families, challenging identification. The pathogenesis, transmission, and clinical manifestations of mpox and other species are similar due to their closely related genetic material. This review provides a comprehensive discussion of the roles of various proteins, including extracellular enveloped virus (EEV), intracellular mature virus (IMV), and profilin-like proteins of mpox. It also highlights recent diagnostic techniques based on these proteins to detect this infection rapidly.
Topics: Monkeypox virus; Humans; Viral Proteins; Mpox (monkeypox); Animals
PubMed: 38863833
DOI: 10.3389/fcimb.2024.1414224 -
Genomics, Proteomics & Bioinformatics May 2024The monkeypox virus (mpox virus, MPXV) epidemic in 2022 has posed a significant public health risk. Yet, the evolutionary principles of MPXV remain largely unknown....
The monkeypox virus (mpox virus, MPXV) epidemic in 2022 has posed a significant public health risk. Yet, the evolutionary principles of MPXV remain largely unknown. Here, we examined the evolutionary patterns of protein sequences and codon usage in MPXV. We first demonstrated the signal of positive selection in OPG027, specifically in the Clade I lineage of MPXV. Subsequently, we discovered accelerated protein sequence evolution over time in the variants responsible for the 2022 outbreak. Furthermore, we showed strong epistasis between amino acid substitutions located in different genes. The codon adaptation index (CAI) analysis revealed that MPXV genes tended to use more non-preferred codons compared to human genes, and the CAI decreased over time and diverged between clades, with Clade I > IIa and IIb-A > IIb-B. While the decrease in fatality rate among the three groups aligned with the CAI pattern, it remains unclear whether this correlation was coincidental or if the deoptimization of codon usage in MPXV led to a reduction in fatality rates. This study sheds new light on the mechanisms that govern the evolution of MPXV in human populations.
Topics: Evolution, Molecular; Codon Usage; Humans; Monkeypox virus; Viral Proteins; Phylogeny; Selection, Genetic; Codon; Amino Acid Sequence; Amino Acid Substitution; Mpox (monkeypox)
PubMed: 38862422
DOI: 10.1093/gpbjnl/qzad003 -
The Journal of General Virology Jun 2024Increased human-to-human transmission of monkeypox virus (MPXV) is cause for concern, and antibodies directed against vaccinia virus (VACV) are known to confer...
Increased human-to-human transmission of monkeypox virus (MPXV) is cause for concern, and antibodies directed against vaccinia virus (VACV) are known to confer cross-protection against Mpox. We used 430 serum samples derived from the Scottish patient population to investigate antibody-mediated cross-neutralization against MPXV. By combining electrochemiluminescence immunoassays with live-virus neutralization assays, we show that people born when smallpox vaccination was routinely offered in the United Kingdom have increased levels of antibodies that cross-neutralize MPXV. Our results suggest that age is a risk factor of Mpox infection, and people born after 1971 are at higher risk of infection upon exposure.
Topics: Humans; Antibodies, Viral; Smallpox Vaccine; Adult; Middle Aged; Monkeypox virus; Young Adult; Antibodies, Neutralizing; Mpox (monkeypox); Female; Adolescent; Aged; Male; Cross Protection; Scotland; Age Factors; Neutralization Tests; Child; Vaccination; Smallpox; Child, Preschool; Cross Reactions; Aged, 80 and over
PubMed: 38861287
DOI: 10.1099/jgv.0.001999 -
Journal of Medical Virology Jun 2024Since May 2022, several countries outside of Africa experienced multiple clusters of monkeypox virus (MPXV)-associated disease. In the present study, anti-MPXV and...
Since May 2022, several countries outside of Africa experienced multiple clusters of monkeypox virus (MPXV)-associated disease. In the present study, anti-MPXV and anti-vaccinia virus (VACV) neutralizing antibody responses were evaluated in two cohorts of subjects from the general Italian population (one half born before the WHO-recommended end of smallpox vaccination in 1980, the other half born after). Higher titers (either against MPXV or VACV) were observed in the cohort of individuals born before the interruption of VACV vaccination. An association between VACV and MPXV antibody levels was observed, suggesting that the smallpox vaccination may confer some degree of cross-protection against MPXV infection. Results from this study highlight low levels of immunity toward the assessed Orthopoxviruses, especially in young adults, advocating the introduction of a VACV- or MPXV-specific vaccine in case of resurgence of monkeypox disease outbreaks.
Topics: Humans; Antibodies, Neutralizing; Antibodies, Viral; Male; Adult; Female; Smallpox Vaccine; Italy; Monkeypox virus; Young Adult; Seroepidemiologic Studies; Middle Aged; Vaccination; Vaccinia virus; Mpox (monkeypox); Adolescent; Smallpox; Cross Protection; Aged; Cohort Studies; Child
PubMed: 38860589
DOI: 10.1002/jmv.29728