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1.
J Immunol Res ; 2022: 3883822, 2022.
Article in English | MEDLINE | ID: mdl-36093436

ABSTRACT

Monkeypox virus (MPV) is a smallpox-like virus belonging to the genus Orthopoxvirus of the family Poxviridae. Unlike smallpox with no animal reservoir identified and patients suffering from milder symptoms with less mortality, several animals were confirmed to serve as natural hosts of MPV. The reemergence of a recently reported monkeypox epidemic outbreak in nonendemic countries has raised concerns about a global outburst. Since the underlying mechanism of animal-to-human transmission remains largely unknown, comprehensive analyses to discover principal differences in gene signatures during disease progression have become ever more critical. In this study, two MPV-infected in vitro models, including human immortal epithelial cancer (HeLa) cells and rhesus monkey (Macaca mulatta) kidney epithelial (MK2) cells, were chosen as the two subjects to identify alterations in gene expression profiles, together with co-regulated genes and pathways that are affected during monkeypox disease progression. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and MetaCore analyses, we discovered that elevated expression of genes associated with interleukins (ILs), G protein-coupled receptors (GPCRs), heat shock proteins (HSPs), Toll-like receptors (TLRs), and metabolic-related pathways play major roles in disease progression of both monkeypox-infected monkey MK2 and human HeLa cell lines. Interestingly, our analytical results also revealed that a cluster of differentiation 40 (CD40), plasmin, and histamine served as major regulators in the monkeypox-infected monkey MK2 cell line model, while interferons (IFNs), macrophages, and neutrophil-related signaling pathways dominated the monkeypox-infected human HeLa cell line model. Among immune pathways of interest, apart from traditional monkeypox-regulated signaling pathways such as nuclear factor- (NF-κB), mitogen-activated protein kinases (MAPKs), and tumor necrosis factors (TNFs), we also identified highly significantly expressed genes in both monkey and human models that played pivotal roles during the progression of monkeypox infection, including CXCL1, TNFAIP3, BIRC3, IL6, CCL2, ZC3H12A, IL11, CSF2, LIF, PTX3, IER3, EGR1, ADORA2A, and DUOX1, together with several epigenetic regulators, such as histone cluster family gene members, HIST1H3D, HIST1H2BJ, etc. These findings might contribute to specific underlying mechanisms related to the pathophysiology and provide suggestions regarding modes of transmission, post-infectious sequelae, and vaccine development for monkeypox in the future.


Subject(s)
Monkeypox , Smallpox , Animals , Disease Progression , HeLa Cells , Humans , Macaca mulatta , Monkeypox/pathology , Monkeypox virus/genetics , Transcriptome
3.
Medicine (Baltimore) ; 101(35): e30406, 2022 Sep 02.
Article in English | MEDLINE | ID: mdl-36107544

ABSTRACT

The human monkeypox is an emerging zoonotic orthopoxvirus with a clinical presentation similar to that of smallpox. It is difficult to differentiate monkeypox from other orthopedic infections, and laboratory diagnosis is the primary component of disease identification and monitoring. However, current diagnostics are time-consuming, and new tests are needed for rapid and precise diagnosis. Most cases have been reported in Central Africa; however, an increasing number of cases have been reported in Europe, the United States of America (USA), Australia, and the United Arab Emirates. Although investigation of the current global outbreak is still ongoing, viral transmission seems to have occurred during crowded events in Spain and Belgium. New therapeutics and vaccines are being deployed for the treatment and prevention of monkeypox, and more research on the epidemiology, biology, and ecology of the virus in endemic areas is required to understand and prevent further global outbreaks.


Subject(s)
Monkeypox , Australia , Disease Outbreaks/prevention & control , Europe , Humans , Monkeypox/diagnosis , Monkeypox/epidemiology , Monkeypox/prevention & control , Monkeypox virus , United States
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(9): 960-966, 2022.
Article in Chinese | MEDLINE | ID: mdl-36111711

ABSTRACT

The guideline for the diagnosis and treatment of monkeypox (2022 edition) issued by National Health Commission of the People's Republic of China introduces the key knowledge of the diagnosis and treatment of human monkeypox (HMPX) and does not systematically introduce the sampling methods and requirements of specimens for HMPX etiology testing and the discrepancy in diagnostic criteria between China and overseas. However, the doctors who are not engaged in dermatology lack understanding of the sampling methods and requirements of specimens for laboratory diagnosis of HMPX, and there are few relevant references available. This article collects the information on the diagnosis and treatment of HMPX, so as to provide a reference for learning, understanding, and application of this guideline.


Subject(s)
Monkeypox , China , Humans , Monkeypox/diagnosis , Monkeypox/therapy
8.
Clin Immunol ; 243: 109108, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36067982

ABSTRACT

Monkeypox is a zoonotic Orthopoxvirus which has predominantly affected humans living in western and central Africa since the 1970s. Type I and II interferon signaling, NK cell function, and serologic immunity are critical for host immunity against monkeypox. Monkeypox can evade host viral recognition and block interferon signaling, leading to overall case fatality rates of up to 11%. The incidence of monkeypox has increased since cessation of smallpox vaccination. In 2022, a global outbreak emerged, predominantly affecting males, with exclusive human-to-human transmission and more phenotypic variability than earlier outbreaks. Available vaccines are safe and effective tools for prevention of severe disease, but supply is limited. Now considered a public health emergency, more studies are needed to better characterize at-risk populations and to develop new anti-viral therapies.


Subject(s)
Communicable Diseases , Monkeypox , Orthopoxvirus , Humans , Interferons , Male , Monkeypox/epidemiology , Monkeypox/prevention & control , Monkeypox virus
12.
Science ; 377(6612): 1261-1263, 2022 09 16.
Article in English | MEDLINE | ID: mdl-36107995

ABSTRACT

A disease anywhere can spread everywhere, if neglected.


Subject(s)
Monkeypox , Humans , Monkeypox/epidemiology , Monkeypox virus
13.
Science ; 377(6612): 1252-1255, 2022 09 16.
Article in English | MEDLINE | ID: mdl-36108009

ABSTRACT

The global monkeypox outbreak is giving the virus an unprecedented opportunity to adapt to humans. Will it change for the worse?


Subject(s)
Monkeypox virus , Monkeypox , Disease Outbreaks , Humans , Monkeypox/epidemiology
16.
17.
Article in English | MEDLINE | ID: mdl-36074449

ABSTRACT

In 2022, an outbreak of monkeypox is being reported in non-endemic areas, with unusual clinical manifestations. The detailed clinical description of the first patient that received the diagnosis of monkeypox in Brazil is reported here, whose clinical manifestations can easily lead to misdiagnosis of sexually transmitted infections. A 41 years old male presented to an emergency room with a vesicular rash with eight days of evolution. He had traveled to Portugal and Spain and reported non-penetrative sexual involvement with three different male individuals. On the third day of symptoms, he sought medical care and received empirical treatment directed to sexually transmitted infections. As the symptoms did not improve, he sought medical attention at an infectious disease referral center presenting, on admission, an ulcerated penile lesion with central necrotic crusts, a disseminated pleomorphic skin rash and an oropharyngeal ulcer. The monkeypox diagnosis was suspected due to the characteristics of the lesions and the history of intimate contact with casual partners, and it was later confirmed by sequencing the almost complete monkeypox genome. The patient was hospitalized for pain control, which required opiate administration. He developed a secondary bacterial infection on the penile lesions, which were treated with oral antibiotics. He was discharged after 14 days, with lesions in process of re-epithelialization. Given the current outbreak, we must consider the possibility of monkeypox in patients with suggestive lesions, anywhere on the body (including the genitals), added to an epidemiological link or history of intimate contact with strangers or casual partners.


Subject(s)
Monkeypox , Sexually Transmitted Diseases , Adult , Animals , Brazil , Diagnosis, Differential , Disease Outbreaks , Humans , Male , Monkeypox/diagnosis , Monkeypox/epidemiology , Monkeypox/pathology , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/epidemiology
18.
MMWR Morb Mortal Wkly Rep ; 71(36): 1141-1147, 2022 Sep 09.
Article in English | MEDLINE | ID: mdl-36074735

ABSTRACT

High prevalences of HIV and other sexually transmitted infections (STIs) have been reported in the current global monkeypox outbreak, which has affected primarily gay, bisexual, and other men who have sex with men (MSM) (1-5). In previous monkeypox outbreaks in Nigeria, concurrent HIV infection was associated with poor monkeypox clinical outcomes (6,7). Monkeypox, HIV, and STI surveillance data from eight U.S. jurisdictions* were matched and analyzed to examine HIV and STI diagnoses among persons with monkeypox and assess differences in monkeypox clinical features according to HIV infection status. Among 1,969 persons with monkeypox during May 17-July 22, 2022, HIV prevalence was 38%, and 41% had received a diagnosis of one or more other reportable STIs in the preceding year. Among persons with monkeypox and diagnosed HIV infection, 94% had received HIV care in the preceding year, and 82% had an HIV viral load of <200 copies/mL, indicating HIV viral suppression. Compared with persons without HIV infection, a higher proportion of persons with HIV infection were hospitalized (8% versus 3%). Persons with HIV infection or STIs are disproportionately represented among persons with monkeypox. It is important that public health officials leverage systems for delivering HIV and STI care and prevention to reduce monkeypox incidence in this population. Consideration should be given to prioritizing persons with HIV infection and STIs for vaccination against monkeypox. HIV and STI screening and other recommended preventive care should be routinely offered to persons evaluated for monkeypox, with linkage to HIV care or HIV preexposure prophylaxis (PrEP) as appropriate.


Subject(s)
HIV Infections , Monkeypox , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Sexually Transmitted Diseases , Animals , HIV Infections/epidemiology , HIV Infections/prevention & control , Homosexuality, Male , Humans , Male , Monkeypox/epidemiology , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/prevention & control
19.
MMWR Morb Mortal Wkly Rep ; 71(36): 1155-1158, 2022 Sep 09.
Article in English | MEDLINE | ID: mdl-36074752

ABSTRACT

Since May 2022, approximately 20,000 cases of monkeypox have been identified in the United States, part of a global outbreak occurring in approximately 90 countries and currently affecting primarily gay, bisexual, and other men who have sex with men (MSM) (1). Monkeypox virus (MPXV) spreads from person to person through close, prolonged contact; a small number of cases have occurred in populations who are not MSM (e.g., women and children), and testing is recommended for persons who meet the suspected case definition* (1). CDC previously developed five real-time polymerase chain reaction (PCR) assays for detection of orthopoxviruses from lesion specimens (2,3). CDC was granted 510(k) clearance for the nonvariola-orthopoxvirus (NVO)-specific PCR assay by the Food and Drug Administration. This assay was implemented within the Laboratory Response Network (LRN) in the early 2000s and became critical for early detection of MPXV and implementation of public health action in previous travel-associated cases as well as during the current outbreak (4-7). PCR assays (NVO and other Orthopoxvirus laboratory developed tests [LDT]) represent the primary tool for monkeypox diagnosis. These tests are highly sensitive, and cross-contamination from other MPXV specimens being processed, tested, or both alongside negative specimens can occasionally lead to false-positive results. This report describes three patients who had atypical rashes and no epidemiologic link to a monkeypox case or known risk factors; these persons received diagnoses of monkeypox based on late cycle threshold (Ct) values ≥34, which were false-positive test results. The initial diagnoses were followed by administration of antiviral treatment (i.e., tecovirimat) and JYNNEOS vaccine postexposure prophylaxis (PEP) to patients' close contacts. After receiving subsequent testing, none of the three patients was confirmed to have monkeypox. Knowledge gained from these and other cases resulted in changes to CDC guidance. When testing for monkeypox in specimens from patients without an epidemiologic link or risk factors or who do not meet clinical criteria (or where these are unknown), laboratory scientists should reextract and retest specimens with late Ct values (based on this report, Ct ≥34 is recommended) (8). CDC can be consulted for complex cases including those that appear atypical or questionable cases and can perform additional viral species- and clade-specific PCR testing and antiorthopoxvirus serologic testing.


Subject(s)
Communicable Diseases , Monkeypox , Orthopoxvirus , Sexual and Gender Minorities , Animals , Child , Female , Homosexuality, Male , Humans , Male , Monkeypox/diagnosis , Monkeypox/epidemiology , Monkeypox virus/genetics , Orthopoxvirus/genetics , Travel , United States/epidemiology
20.
Ann Acad Med Singap ; 51(8): 456-457, 2022 08.
Article in English | MEDLINE | ID: mdl-36047518
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