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Trends in Pharmacological Sciences Oct 2023Since May 2022, mpox virus (MPXV) has attracted considerable attention due to a multi-country outbreak. Marked differences in epidemiology, transmission, and pathology... (Review)
Review
Since May 2022, mpox virus (MPXV) has attracted considerable attention due to a multi-country outbreak. Marked differences in epidemiology, transmission, and pathology between the 2022 global mpox outbreak (clade IIb) and classical mpox disease, endemic in Africa (clades I and IIa) have been highlighted. MPXV genome analysis has identified the genomic changes characterizing clade IIb and the drivers of MPXV rapid evolution. Although mpox cases have largely declined, MPXV cryptic transmission and microevolution continues, which may lead to an MPXV of unpredictable pathogenicity. Vaccines and antivirals developed against variola virus, the agent that caused the extinguished plague smallpox, have been used to contain the 2022 mpox outbreak. In this review article, recent findings on MPXV origin and evolution and relevant models able to recapitulate differences in MPXV pathogenicity, which are important for drug and vaccine development, are discussed.
Topics: Humans; Virulence; Monkeypox virus; Mpox (monkeypox); Drug Discovery; Vaccine Development
PubMed: 37673695
DOI: 10.1016/j.tips.2023.08.003 -
Nature Communications Oct 2023The recent monkeypox virus (MPXV) outbreak was of global concern and has mainly affected gay, bisexual and other men who have sex with men (GBMSM). Here we assess...
The recent monkeypox virus (MPXV) outbreak was of global concern and has mainly affected gay, bisexual and other men who have sex with men (GBMSM). Here we assess prevalence of MPXV in high-risk populations of GBMSM, trans women (TW) and non-binary people without symptoms or with unrecognized monkeypox (Mpox) symptoms, using a self-sampling strategy. Anal and pharyngeal swabs are tested by MPXV real-time PCR and positive samples are tested for cytopathic effect (CPE) in cell culture. 113 individuals participated in the study, 89 (78.76%) were cis men, 17 (15.04%) were TW. The median age was 35.0 years (IQR: 30.0-43.0), 96 (85.02%) individuals were gay or bisexual and 72 (63.72%) were migrants. Seven participants were MPXV positive (6.19% (95% CI: 1.75%-10.64%)). Five tested positive in pharyngeal swabs, one in anal swab and one in both. Six did not present symptoms recognized as MPXV infection. Three samples were positive for CPE, and showed anti-vaccinia pAb staining by FACS and confocal microscopy. This suggests that unrecognized Mpox cases can shed infectious virus. Restricting testing to individuals reporting Mpox symptoms may not be sufficient to contain outbreaks.
Topics: Male; Humans; Female; Adult; Spain; Homosexuality, Male; Mpox (monkeypox); Monkeypox virus; Sexual and Gender Minorities
PubMed: 37783731
DOI: 10.1038/s41467-023-40490-9 -
Nature Microbiology Jun 2024Historically, monkeypox (mpox) was a zoonotic disease endemic in Africa. However, in 2022, a global outbreak occurred following a substantial increase in cases in... (Review)
Review
Historically, monkeypox (mpox) was a zoonotic disease endemic in Africa. However, in 2022, a global outbreak occurred following a substantial increase in cases in Africa, coupled with spread by international travellers to other continents. Between January 2022 and October 2023, about 91,000 confirmed cases from 115 countries were reported, leading the World Health Organization to declare a public health emergency. The basic biology of monkeypox virus (MPXV) can be inferred from other poxviruses, such as vaccinia virus, and confirmed by genome sequencing. Here the biology of MPXV is reviewed, together with a discussion of adaptive changes during MPXV evolution and implications for transmission. Studying MPXV biology is important to inform specific host interactions, to aid in ongoing outbreaks and to predict those in the future.
Topics: Monkeypox virus; Mpox (monkeypox); Disease Outbreaks; Humans; Animals; Zoonoses; Genome, Viral; Africa; Phylogeny
PubMed: 38724757
DOI: 10.1038/s41564-024-01690-1 -
Proceedings of the National Academy of... Feb 2024Monkeypox virus (MPXV) infections in humans cause neurological disorders while studies of MPXV-infected animals indicate that the virus penetrates the brain. Pyroptosis...
Monkeypox virus (MPXV) infections in humans cause neurological disorders while studies of MPXV-infected animals indicate that the virus penetrates the brain. Pyroptosis is an inflammatory type of regulated cell death, resulting from plasma membrane rupture (PMR) due to oligomerization of cleaved gasdermins to cause membrane pore formation. Herein, we investigated the human neural cell tropism of MPXV compared to another orthopoxvirus, vaccinia virus (VACV), as well as its effects on immune responses and cell death. Astrocytes were most permissive to MPXV (and VACV) infections, followed by microglia and oligodendrocytes, with minimal infection of neurons based on plaque assays. Aberrant morphological changes were evident in MPXV-infected astrocytes that were accompanied with viral protein (I3) immunolabelling and detection of over 125 MPXV-encoded proteins in cell lysates by mass spectrometry. MPXV- and VACV-infected astrocytes showed increased expression of immune gene transcripts (, and ). However, MPXV infection of astrocytes specifically induced proteolytic cleavage of gasdermin B (GSDMB) (50 kDa), evident by the appearance of cleaved N-terminal-GSDMB (30 kDa) and C-terminal- GSDMB (18 kDa) fragments. GSDMB cleavage was associated with release of lactate dehydrogenase and increased cellular nucleic acid staining, indicative of PMR. Pre-treatment with dimethyl fumarate reduced cleavage of GSDMB and associated PMR in MPXV-infected astrocytes. Human astrocytes support productive MPXV infection, resulting in inflammatory gene induction with accompanying GSDMB-mediated pyroptosis. These findings clarify the recently recognized neuropathogenic effects of MPXV in humans while also offering potential therapeutic options.
Topics: Animals; Humans; Monkeypox virus; Mpox (monkeypox); Pyroptosis; Astrocytes; Gasdermins
PubMed: 38346199
DOI: 10.1073/pnas.2315653121 -
NEJM Evidence Mar 2024The multinational outbreak of mpox (formerly known as monkeypox) that began in 2022 resulted in more than 90,000 reported cases, over 150 deaths, and - importantly - a...
The multinational outbreak of mpox (formerly known as monkeypox) that began in 2022 resulted in more than 90,000 reported cases, over 150 deaths, and - importantly - a coordinated international response to a rapidly spreading infectious disease. Because of decades of global preparedness efforts, vaccines and therapeutics for a related orthopox virus (smallpox) were available in many global stockpiles. Few of these medical countermeasures were specifically designed, evaluated, or approved for use against mpox disease, requiring the global scientific community to identify how best to quickly translate what was known into what was needed.
Topics: Humans; Mpox (monkeypox); Disease Outbreaks; Medical Countermeasures; Orthopoxvirus; Smallpox
PubMed: 38411451
DOI: 10.1056/EVIDe2300357 -
The Annals of Pharmacotherapy Oct 2023This article reviews the published data encompassing the development, pharmacology, efficacy, and safety of brincidofovir, a nucleotide analogue DNA polymerase inhibitor... (Review)
Review
OBJECTIVE
This article reviews the published data encompassing the development, pharmacology, efficacy, and safety of brincidofovir, a nucleotide analogue DNA polymerase inhibitor developed for the treatment of smallpox.
DATA SOURCES
A literature review was conducted in PubMed, MEDLINE, and Clinicaltrials.gov from inception up to December 2022, using terms , and .
STUDY SELECTION AND DATA EXTRACTION
Data were limited to studies published in English language, which evaluated the efficacy and safety of brincidofovir.
DATA SYNTHESIS
Two surrogate animal models were included in the Food and Drug Administration's (FDA) decision to approve brincidofovir: ectromelia virus in mice and rabbitpox in rabbits. Phases 2 and 3 studies established safety for approval. Brincidofovir biweekly for the treatment of disseminated adenovirus disease resulted in all-cause mortality, ranging from 13.8% to 29%. In a study for cytomegalovirus prophylaxis, patients with clinically significant cytomegalovirus infection through week 24 posttransplant was 51.2% with brincidofovir and 52.3% with placebo.
CONCLUSIONS
Brincidofovir adds a second oral agent to treat smallpox, with a different mechanism of action than tecovirimat. In the event of a smallpox outbreak, prompt treatment will be necessary to contain its spread. Brincidofovir shows efficacy in surrogate animal models. In healthy volunteers and individuals treated, or used as prophylaxis, for cytomegalovirus or adenovirus, the primary adverse events were gastrointestinal in addition to transient hepatotoxicity. Additionally, excessive deaths were observed in hematopoietic cell transplant patients receiving it as cytomegalovirus prophylaxis, requiring a black box warning.
Topics: Humans; Rabbits; Animals; Mice; Smallpox; Hematopoietic Stem Cell Transplantation; Antiviral Agents; Disease Models, Animal; Variola virus; Cytosine; Cytomegalovirus
PubMed: 36688308
DOI: 10.1177/10600280231151751 -
Anais Brasileiros de Dermatologia 2023
Topics: Humans; Mpox (monkeypox); Skin Diseases
PubMed: 37225625
DOI: 10.1016/j.abd.2023.04.001 -
The Lancet. Infectious Diseases Dec 2023
Topics: Humans; Mpox (monkeypox)
PubMed: 37625432
DOI: 10.1016/S1473-3099(23)00487-5 -
Iranian Journal of Medical Sciences Jan 2024Monkeypox is an infectious and contagious zoonotic disease caused by the Orthopoxvirus species and was first identified in Africa. Recently, this infectious disease has... (Review)
Review
Monkeypox is an infectious and contagious zoonotic disease caused by the Orthopoxvirus species and was first identified in Africa. Recently, this infectious disease has spread widely in many parts of the world. Fever, fatigue, headache, and rash are common symptoms of monkeypox. The presence of lymphadenopathy is another prominent and key symptom of monkeypox, which distinguishes this disease from other diseases and is useful for diagnosing the disease. This disease is transmitted to humans through contact with or eating infected animals as well as objects infected with the virus. One of the ways to diagnose this disease is through PCR testing of lesions and secretions. To prevent the disease, vaccines such as JYNNEOS and ACAM2000 are available, but they are not accessible to all people in the world, and their effectiveness and safety need further investigation. However, preventive measures such as avoiding contact with people infected with the virus and using appropriate personal protective equipment are mandatory. The disease therapy is based on medicines such as brincidofovir, cidofovir, and Vaccinia Immune Globulin Intravenous. The injectable format of tecovirimat was approved recently, in May 2022. Considering the importance of clinical care in this disease, awareness about the side effects of medicines, nutrition, care for conjunctivitis, skin rash, washing and bathing at home, and so on can be useful in controlling and managing the disease.
Topics: Humans; Animals; Mpox (monkeypox); Administration, Intravenous; Africa; Benzamides; Cidofovir; Exanthema
PubMed: 38322157
DOI: 10.30476/IJMS.2022.96738.2837 -
General Dentistry 2024The zoonotic infectious disease mpox (previously known as monkeypox) is caused by the monkeypox virus (MPXV) from the Poxviridae family. Presently, mpox is receiving...
The zoonotic infectious disease mpox (previously known as monkeypox) is caused by the monkeypox virus (MPXV) from the Poxviridae family. Presently, mpox is receiving worldwide attention because of its emergence in countries that have never previously documented the illness, resulting in a public health emergency. MPXV is transmitted via human-to-human contact, and sexual contact is especially implicated in spread of the disease. Affected individuals experience fever, headache, malaise, and early lymphadenopathy, followed by a secondary mucotaneous rash. Oral ulcers and perioral papules may be the first evidence of the disease. Although there are numerous articles in medical publications documenting the cutaneous presentations of mpox, there is limited information in the dental literature regarding oral lesions. The objective of this article is to review the oral manifestations of mpox and strategies for management of the disease.
Topics: Humans; Mpox (monkeypox); Oral Ulcer; Public Health
PubMed: 38411483
DOI: No ID Found