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Environment International May 2024The Chicago Department of Public Health tested wastewater samples for the presence of Monkeypox Virus (MPXV) from March 13 through June 26, 2023. There were persistent...
The Chicago Department of Public Health tested wastewater samples for the presence of Monkeypox Virus (MPXV) from March 13 through June 26, 2023. There were persistent detections prior to reported cases. This indicated the baseline levels of MPXV prevalence might warrant routine monitoring. Detections in areas without corresponding reported clinical cases might highlight areas where cases are being under-reported by traditional surveillance.
PubMed: 38885552
DOI: 10.1016/j.envint.2024.108749 -
Indian Journal of Otolaryngology and... Jun 2024A case of mpox pharyngitis in absence of cutaneous lesions is reported. Usually, clinical presentation is either a cutaneous eruption or a combination of cutaneous and...
A case of mpox pharyngitis in absence of cutaneous lesions is reported. Usually, clinical presentation is either a cutaneous eruption or a combination of cutaneous and mucosal lesions. In patients with atypical pharyngitis, regardless of the presence of skin lesions, pharyngeal swabs should be collected to rule out mpox.
PubMed: 38883515
DOI: 10.1007/s12070-024-04567-1 -
International Journal of Infectious... Jun 2024Monkeypox (Mpox) is a neglected viral endemic tropical disease in both Central and Western African countries transmitted to humans by an animal. However, the natural...
Monkeypox (Mpox) is a neglected viral endemic tropical disease in both Central and Western African countries transmitted to humans by an animal. However, the natural reservoir of the virus remains elusive. In this study we looked for potential reservoirs of MPXV in Gabonese wildlife to prevent future outbreaks and enrich the literature with additional data on animal reservoirs. DNA was extracted from livers and spleens from 2549 animals (bats (859), bushmeats (356), rodents (1309), and shrews (25)) collected between 2012 and 2021. DNA was analyzed by real-time and conventional PCR targeting the 14 KD Protein and the rpo subunit RNA polymerase of orthopoxviruses. No MPXV DNA was detected despite the presence of potential host reservoirs like Critcetomys, Crocidura, Praomys, and Atherurus africanus. This absence could be due to: (i) the low number of animals collected for some species, (ii) the acute nature of Mpox infection, but also (iii) the lack of the potential reservoir Funisciurus anerythrus among collected animals, and (iv) the fact that the samplings are not included in the probable ecological niche of MPXV. Longitudinal studies including potential ecological niches of both F. anerythrus and MPXV in Gabon may be useful to get more information on MPXV circulation.
PubMed: 38878993
DOI: 10.1016/j.ijid.2024.107106 -
Emerging Microbes & Infections Dec 2024The global outbreak of Mpox, caused by the monkeypox virus (MPXV), has attracted international attention and become another major infectious disease event after...
The global outbreak of Mpox, caused by the monkeypox virus (MPXV), has attracted international attention and become another major infectious disease event after COVID-19. The mRNA cap N7 methyltransferase (RNMT) of MPXV methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs and plays a vital role in evading host antiviral immunity. MPXV RNMT is composed of the large subunit E1 and the small subunit E12. How E1 and E12 of MPXV assembly remains unclear. Here, we report the crystal structures of E12, the MTase domain of E1 with E12 (E1-E12) complex, and the E1-E12-SAM ternary complex, revealing the detailed conformations of critical residues and the structural changes upon E12 binding to E1. Functional studies suggest that E1 N-terminal extension (Asp545-Arg562) and the small subunit E12 play an essential role in the binding process of SAM. Structural comparison of the AlphaFold2-predicted E1, E1-E12 complex, and the homologous D1-D12 complex of vaccinia virus (VACV) indicates an allosteric activating effect of E1 in MPXV. Our findings provide the structural basis for the MTase activity stimulation of the E1-E12 complex and suggest a potential interface for screening the anti-poxvirus inhibitors.
Topics: Methyltransferases; Monkeypox virus; Viral Proteins; Crystallography, X-Ray; RNA Caps; Models, Molecular; Humans; Protein Conformation; Protein Binding; RNA, Messenger
PubMed: 38873898
DOI: 10.1080/22221751.2024.2369193 -
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 -
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 -
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 -
The Lancet. Microbe Jun 2024Since the emergence of the global mpox outbreak in May, 2022, more than 90 000 cases have been diagnosed across 110 countries, disproportionately affecting people with...
BACKGROUND
Since the emergence of the global mpox outbreak in May, 2022, more than 90 000 cases have been diagnosed across 110 countries, disproportionately affecting people with HIV. The durability of mpox-specific immunity is unclear and reinfections have been reported. We aimed to compare mpox immune responses up to 6 months after diagnosis in participants with and without HIV and assess their effect on disease severity and viral clearance dynamics.
METHODS
This study was embedded within a prospective, observational, multicentre cohort study of viral clearance dynamics among people with mpox in Spain (MoViE). We included women and men aged 18 years or older, who had signs of mpox, and reported having symptom onset within the previous 10 days at the moment of mpox diagnosis from three sex clinics of the Barcelona metropolitan area. Samples from skin ulcers were collected weekly to estimate the time to clear monkeypox virus (MPXV) from skin lesions. Blood samples were taken at diagnosis, 29, 91, and 182 days later for immune analysis. This included quantifying IgG and IgA against three mpox antigens by ELISA, evaluating in-vitro neutralisation, and characterising mpox-specific T-cell responses using interferon γ detecting enzyme-linked immunospot (ELISpot) assay and multiparametric flow cytometry.
FINDINGS
Of the 77 originally enrolled participants, we included 33 participants recruited between July 19, and Oct 6, 2022. Participants without HIV (19 [58%] participants) and participants with HIV (14 [42%] participants) had similar clinical severity and time to MPXV clearance in skin lesions. Participants with HIV had a CD4 T-cell count median of 777 cells per μL (IQR 484-1533), and 11 (78%) of 14 were virally suppressed on antiretroviral therapy. Nine (27%) of 33 participants were age 49 years or older. 15 (45%) of 33 participants were originally from Spain, and all participants were men. Early humoral responses, particularly concentrations and breadth of IgG and IgA, were associated with milder disease and faster viral clearance. Orthopoxvirus-specific T cells count was also positively correlated with MPXV clearance. Antibody titres declined more rapidly in participants with HIV, but T-cell responses against MPXV were sustained up to day 182 after diagnosis, regardless of HIV status.
INTERPRETATION
Higher breadth and magnitude of B-cell and T-cell responses are important in facilitating local viral clearance, limiting mpox dissemination, and reducing disease severity in individuals with preserved immune system. Antibodies appear to contribute to early viral control and T-cell responses are sustained over time, which might contribute to milder presentations during reinfection.
FUNDING
Fundació Lluita contra les Infeccions, IrsiCaixa, and Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación e Universidades.
PubMed: 38857615
DOI: 10.1016/S2666-5247(24)00074-0 -
Cureus May 2024The case report discusses a 29-year-old male with advanced HIV who experienced one of the longest, confirmed cases of monkeypox (mpox) infection. Despite treatment with...
The case report discusses a 29-year-old male with advanced HIV who experienced one of the longest, confirmed cases of monkeypox (mpox) infection. Despite treatment with antivirals and supportive care, including intravenous tecovirimat and vaccinia immune globulin, the patient's condition worsened over a six-and-a-half-month period. He suffered from widespread ulcerative, necrotic lesions and multiple complications, including acute kidney injury, multi-drug resistant bacterial infections, and respiratory failure. Despite repeated treatments, including brincidofovir, the patient remained PCR-positive for monkeypox virus (MPXV) with low cycle threshold (Ct) values, indicating active infection. The case underscores the severity of mpox in immunocompromised individuals, particularly those with advanced HIV, and highlights the challenges in managing such cases. The patient's persistently low CD4 count and unsuppressed HIV viral load likely contributed to the inability to clear the virus. The report emphasizes the need for further research to optimize treatment strategies for MPXV infection, especially in people living with HIV.
PubMed: 38854169
DOI: 10.7759/cureus.59947