Viruses

Research

13 pages, 4070 KiB

Open AccessArticle

Lives of Skin Lesions in Monkeypox: Histomorphological, Immunohistochemical, and Clinical Correlations in a Small Case Series

by Paul Schmidle, Sonja Leson, Ulrike Wieland, Almut Böer-Auer, Dieter Metze and Stephan A. Braun

Viruses 2023, 15(8), 1748; https://doi.org/10.3390/v15081748 - 15 Aug 2023

Cited by 8 | Viewed by 6627

Abstract

Monkeypox (mpox), a former rare viral zoonosis, has increasingly made it into the public eye since the major outbreak that started in May 2022. Mpox presents with skin lesions that change over time and go through different stages (macular, papular, pustular, and early [...] Read more.

Monkeypox (mpox), a former rare viral zoonosis, has increasingly made it into the public eye since the major outbreak that started in May 2022. Mpox presents with skin lesions that change over time and go through different stages (macular, papular, pustular, and early and late ulceration). In this study, we evaluated skin biopsies of all stages. Therefore, five biopsies from four patients were analyzed histologically, immunohistochemically with anti-Vaccinia virus antibodies, and electron-microscopically. Notably, the early macular stage only showed subtle viropathic changes; it did not express of Orthopoxvirus proteins in immunohistochemistry and therefore can easily be missed histologically. In later stages, immunohistochemistry with anti-Vaccinia virus antibodies might be useful to distinguish mpox from differential diagnoses such as herpes virus infections. In the ulcerative stages, the identified occlusive vasculopathic changes could be an explanation for the severe pain of the lesions reported by some patients. Despite the small number of samples examined, our analysis suggests that the histological findings of mpox are highly dependent on the stage of the biopsied lesion. Therefore, knowledge of all different stages of histology is necessary to reliably diagnose mpox histologically, especially when molecular testing is not available. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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11 pages, 4315 KiB

Open AccessCommunication

Mpox (Monkeypox) in Pregnancy: Viral Clade Differences and Their Associations with Varying Obstetrical and Fetal Outcomes

by David A. Schwartz and Phillip R. Pittman

Viruses 2023, 15(8), 1649; https://doi.org/10.3390/v15081649 - 28 Jul 2023

Cited by 7 | Viewed by 3152

Abstract

In African countries where mpox (monkeypox) is endemic, infection is caused by two genetically related clades—Clade I (formerly Congo Basin), and Clade IIa (formerly West Africa), both of which are potentially life-threatening infections. Prior to the 2022–2023 global outbreak, mpox infections among pregnant [...] Read more.

In African countries where mpox (monkeypox) is endemic, infection is caused by two genetically related clades—Clade I (formerly Congo Basin), and Clade IIa (formerly West Africa), both of which are potentially life-threatening infections. Prior to the 2022–2023 global outbreak, mpox infections among pregnant women caused by Clade I were reported to have a 75% perinatal case fatality rate in the Democratic Republic of Congo, including the only documented case of placental infection and stillbirth from the Congenital Mpox Syndrome, and the Clade IIa mpox infection was associated with stillbirths in Nigeria. The 2022–2023 global mpox outbreak, caused by a genetically distinct strain, Clade IIb, has focused attention on the effects of mpox on pregnant women and fetal outcomes. There have been at least 58 cases of mpox infection occurring in pregnant women during the 2022–2023 outbreak. No confirmed cases of adverse perinatal outcome, including stillbirth, have been reported. The absence of perinatal morbidity and mortality from Clade IIb corresponds to the overall case fatality rate among non-pregnant women of <0.1%, as this clade has been demonstrated to produce a less-severe disease than the mpox Clade I or IIa variants. Thus, there are apparently important differences between mpox clades affecting pregnant women and perinatal outcomes. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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17 pages, 1392 KiB

Open AccessArticle

Identifying the Most Probable Mammal Reservoir Hosts for Monkeypox Virus Based on Ecological Niche Comparisons

by Manon Curaudeau, Camille Besombes, Emmanuel Nakouné, Arnaud Fontanet, Antoine Gessain and Alexandre Hassanin

Viruses 2023, 15(3), 727; https://doi.org/10.3390/v15030727 - 11 Mar 2023

Cited by 14 | Viewed by 3573

Abstract

Previous human cases or epidemics have suggested that Monkeypox virus (MPXV) can be transmitted through contact with animals of African rainforests. Although MPXV has been identified in many mammal species, most are likely secondary hosts, and the reservoir host has yet to be [...] Read more.

Previous human cases or epidemics have suggested that Monkeypox virus (MPXV) can be transmitted through contact with animals of African rainforests. Although MPXV has been identified in many mammal species, most are likely secondary hosts, and the reservoir host has yet to be discovered. In this study, we provide the full list of African mammal genera (and species) in which MPXV was previously detected, and predict the geographic distributions of all species of these genera based on museum specimens and an ecological niche modelling (ENM) method. Then, we reconstruct the ecological niche of MPXV using georeferenced data on animal MPXV sequences and human index cases, and conduct overlap analyses with the ecological niches inferred for 99 mammal species, in order to identify the most probable animal reservoir. Our results show that the MPXV niche covers three African rainforests: the Congo Basin, and Upper and Lower Guinean forests. The four mammal species showing the best niche overlap with MPXV are all arboreal rodents, including three squirrels: Funisciurus anerythrus, Funisciurus pyrropus, Heliosciurus rufobrachium, and Graphiurus lorraineus. We conclude that the most probable MPXV reservoir is F. anerythrus based on two niche overlap metrics, the areas of higher probabilities of occurrence, and available data on MPXV detection. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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12 pages, 2037 KiB

Open AccessArticle

Development of a Novel Loop-Mediated Isothermal Amplification Method for the Rapid Detection of Monkeypox Virus Infections

by Chao Yu, Lulu Zuo, Jing Miao, Lingjing Mao, Benjamin Selekon, Ella Gonofio, Emmanuel Nakoune, Nicolas Berthet and Gary Wong

Viruses 2023, 15(1), 84; https://doi.org/10.3390/v15010084 - 28 Dec 2022

Cited by 11 | Viewed by 3166

Abstract

A recent outbreak of monkeypox virus (mpox) has prompted researchers to explore diagnostics as a means of impeding transmission and further spread. Rapid, sensitive, and specific methods are crucial for accurately diagnosing mpox infections. Here, we developed a loop-mediated isothermal amplification (LAMP) assay [...] Read more.

A recent outbreak of monkeypox virus (mpox) has prompted researchers to explore diagnostics as a means of impeding transmission and further spread. Rapid, sensitive, and specific methods are crucial for accurately diagnosing mpox infections. Here, we developed a loop-mediated isothermal amplification (LAMP) assay for the specific detection of mpox. The primer sets were designed to target regions in and around the N4R gene, and results showed a detection limit of 2 × 10⁰ DNA copies, which is comparable to the gold-standard qPCR method currently used to detect mpox. Particularly, the assay provides results visible to the naked eye within 30 min. This test specifically detects mpox DNA with no cross-reactivity to related DNA viruses including Varicella Zoster Virus (VZV), Hepatitis B virus (HBV), Vaccinia virus (VACV), Herpes simplex virus-1 (HSV-1), Herpes simplex virus-2 (HSV-2), Human papillomavirus-16 (HPV-16) and Human papillomavirus-18 (HPV-18). Furthermore, the LAMP assay has been evaluated using clinical samples from laboratory-confirmed mpox patients and found to be consistent with the qPCR results. Our results show that this single-tube LAMP method can contribute to diagnosis of suspected mpox infections in the field and clinic, especially in regions with limited laboratory resources. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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15 pages, 6881 KiB

Open AccessArticle

A Customized Monkeypox Virus Genomic Database (MPXV DB v1.0) for Rapid Sequence Analysis and Phylogenomic Discoveries in CLC Microbial Genomics

by Jane Shen-Gunther, Hong Cai and Yufeng Wang

Viruses 2023, 15(1), 40; https://doi.org/10.3390/v15010040 - 22 Dec 2022

Cited by 6 | Viewed by 3896

Abstract

Monkeypox has been a neglected, zoonotic tropical disease for over 50 years. Since the 2022 global outbreak, hundreds of human clinical samples have been subjected to next-generation sequencing (NGS) worldwide with raw data deposited in public repositories. However, sequence analysis for in-depth investigation [...] Read more.

Monkeypox has been a neglected, zoonotic tropical disease for over 50 years. Since the 2022 global outbreak, hundreds of human clinical samples have been subjected to next-generation sequencing (NGS) worldwide with raw data deposited in public repositories. However, sequence analysis for in-depth investigation of viral evolution remains hindered by the lack of a curated, whole genome Monkeypox virus (MPXV) database (DB) and efficient bioinformatics pipelines. To address this, we developed a customized MPXV DB for integration with “ready-to-use” workflows in the CLC Microbial Genomics Module for whole genomic and metagenomic analysis. After database construction (218 MPXV genomes), whole genome alignment, pairwise comparison, and evolutionary analysis of all genomes were analyzed to autogenerate tabular outputs and visual displays (collective runtime: 16 min). The clinical utility of the MPXV DB was demonstrated by using a Chimpanzee fecal, hybrid-capture NGS dataset (publicly available) for metagenomic, phylogenomic, and viral/host integration analysis. The clinically relevant MPXV DB embedded in CLC workflows proved to be a rapid method of sequence analysis useful for phylogenomic exploration and a wide range of applications in translational science. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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18 pages, 3111 KiB

Open AccessArticle

Immunoinformatics-Aided Design of a Peptide Based Multiepitope Vaccine Targeting Glycoproteins and Membrane Proteins against Monkeypox Virus

by Nahid Akhtar, Vikas Kaushik, Ravneet Kaur Grewal, Atif Khurshid Wani, Chonticha Suwattanasophon, Kiattawee Choowongkomon, Romina Oliva, Abdul Rajjak Shaikh, Luigi Cavallo and Mohit Chawla

Viruses 2022, 14(11), 2374; https://doi.org/10.3390/v14112374 - 27 Oct 2022

Cited by 32 | Viewed by 3911

Abstract

Monkeypox is a self-limiting zoonotic viral disease and causes smallpox-like symptoms. The disease has a case fatality ratio of 3–6% and, recently, a multi-country outbreak of the disease has occurred. The currently available vaccines that have provided immunization against monkeypox are classified as [...] Read more.

Monkeypox is a self-limiting zoonotic viral disease and causes smallpox-like symptoms. The disease has a case fatality ratio of 3–6% and, recently, a multi-country outbreak of the disease has occurred. The currently available vaccines that have provided immunization against monkeypox are classified as live attenuated vaccinia virus-based vaccines, which pose challenges of safety and efficacy in chronic infections. In this study, we have used an immunoinformatics-aided design of a multi-epitope vaccine (MEV) candidate by targeting monkeypox virus (MPXV) glycoproteins and membrane proteins. From these proteins, seven epitopes (two T-helper cell epitopes, four T-cytotoxic cell epitopes and one linear B cell epitopes) were finally selected and predicted as antigenic, non-allergic, interferon-γ activating and non-toxic. These epitopes were linked to adjuvants to design a non-allergic and antigenic candidate MPXV-MEV. Further, molecular docking and molecular dynamics simulations predicted stable interactions between predicted MEV and human receptor TLR5. Finally, the immune-simulation analysis showed that the candidate MPXV-MEV could elicit a human immune response. The results obtained from these in silico experiments are promising but require further validation through additional in vivo experiments. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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12 pages, 1196 KiB

Open AccessArticle

Development and Characterization of Recombinase-Based Isothermal Amplification Assays (RPA/RAA) for the Rapid Detection of Monkeypox Virus

by Lingjing Mao, Jiaxu Ying, Benjamin Selekon, Ella Gonofio, Xiaoxia Wang, Emmanuel Nakoune, Gary Wong and Nicolas Berthet

Viruses 2022, 14(10), 2112; https://doi.org/10.3390/v14102112 - 23 Sep 2022

Cited by 33 | Viewed by 4917

Abstract

Monkeypox is a zoonotic disease caused by monkeypox virus (MPXV), in which outbreaks mainly occurred in West and Central Africa, with only sporadic spillovers to countries outside Africa due to international travel or close contact with wildlife. During May 2022, multiple countries in [...] Read more.

Monkeypox is a zoonotic disease caused by monkeypox virus (MPXV), in which outbreaks mainly occurred in West and Central Africa, with only sporadic spillovers to countries outside Africa due to international travel or close contact with wildlife. During May 2022, multiple countries in Europe, North and South America, Australia, Asia, and Africa reported near-simultaneous outbreaks of MPXV, the first time that patient clusters were reported over such a large geographical area. Cases have no known epidemiological links to MPXV-endemic countries in West or Central Africa. Real-time PCR is currently the gold standard for MPXV diagnostics, but it requires trained laboratory personnel and specialized equipment, and results can only be obtained after several hours. A rapid and simple-to-operate point-of-care diagnostic test for MPXV is crucial for limiting its spread and controlling outbreaks. Here, three recombinase-based isothermal amplification assays (RPA/RAA) for the rapid detection of MPXV isolates were developed. These three assays target the MPXV G2R gene, and the limit of detection for these systems is approximately 10⁰ copies of DNA per reaction. The assays were found to be specific and non-cross reactive against other pox viruses, such as vaccinia virus, and the results can be visualized within 20–30 min. The assays were validated with DNA extracted from 19 clinical samples from suspected or confirmed MPXV patients from Central Africa, and found to be consistent with findings from traditional qPCR. These results provide a solid platform for the early diagnosis of potential MPXV cases, and will help with the control and prevention of current and future outbreaks. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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19 pages, 2595 KiB

Open AccessArticle

Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus

by Eric M. Mucker, Josh D. Shamblin, Arthur J. Goff, Todd M. Bell, Christopher Reed, Nancy A. Twenhafel, Jennifer Chapman, Marc Mattix, Derron Alves, Robert F. Garry and Lisa E. Hensley

Viruses 2022, 14(9), 1993; https://doi.org/10.3390/v14091993 - 9 Sep 2022

Cited by 7 | Viewed by 3419

Abstract

The 2022 global human monkeypox outbreak emphasizes the importance of maintaining poxvirus research, including enriching a basic understanding of animal models for developing and advancing therapeutics and vaccines. Intravenous administration of monkeypox virus in macaques is arguably one of the best animal models [...] Read more.

The 2022 global human monkeypox outbreak emphasizes the importance of maintaining poxvirus research, including enriching a basic understanding of animal models for developing and advancing therapeutics and vaccines. Intravenous administration of monkeypox virus in macaques is arguably one of the best animal models for evaluating the efficacy of medical countermeasures. Here we addressed one criticism of the model, a requirement for a high-titer administration of virus, as well as improving our understanding of monkeypox virus pathogenesis. To do so, we infected macaques with a challenge dose containing a characterized inoculum enriched for the extracellular form of monkeypox virus. Although there were some differences between diseases caused by the enriched preparation compared with a relatively similar unpurified preparation, we were unable to reduce the viral input with the enriched preparation and maintain severe disease. We found that inherent factors contained within the serum of nonhuman primate blood affect the stability of the monkeypox extracellular virions. As a first step to study a role of the extracellular form in transmission, we also showed the presence of this form in the oropharyngeal swabs from nonhuman primates exposed to monkeypox virus. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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11 pages, 1868 KiB

Open AccessArticle

Vaccinia-Virus-Based Vaccines Are Expected to Elicit Highly Cross-Reactive Immunity to the 2022 Monkeypox Virus

by Syed Faraz Ahmed, Muhammad Saqib Sohail, Ahmed Abdul Quadeer and Matthew R. McKay

Viruses 2022, 14(9), 1960; https://doi.org/10.3390/v14091960 - 3 Sep 2022

Cited by 45 | Viewed by 9203

Abstract

Beginning in May 2022, a novel cluster of monkeypox virus infections was detected in humans. This virus has spread rapidly to non-endemic countries, sparking global concern. Specific vaccines based on the vaccinia virus (VACV) have demonstrated high efficacy against monkeypox viruses in the [...] Read more.

Beginning in May 2022, a novel cluster of monkeypox virus infections was detected in humans. This virus has spread rapidly to non-endemic countries, sparking global concern. Specific vaccines based on the vaccinia virus (VACV) have demonstrated high efficacy against monkeypox viruses in the past and are considered an important outbreak control measure. Viruses observed in the current outbreak carry distinct genetic variations that have the potential to affect vaccine-induced immune recognition. Here, by investigating genetic variation with respect to orthologous immunogenic vaccinia-virus proteins, we report data that anticipates immune responses induced by VACV-based vaccines, including the currently available MVA-BN and ACAM2000 vaccines, to remain highly cross-reactive against the newly observed monkeypox viruses. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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10 pages, 2923 KiB

Open AccessCommunication

Rapid Amplicon Nanopore Sequencing (RANS) for the Differential Diagnosis of Monkeypox Virus and Other Vesicle-Forming Pathogens

by Ofir Israeli, Yehoudit Guedj-Dana, Ohad Shifman, Shirley Lazar, Inbar Cohen-Gihon, Sharon Amit, Ronen Ben-Ami, Nir Paran, Ofir Schuster, Shay Weiss, Anat Zvi and Adi Beth-Din

Viruses 2022, 14(8), 1817; https://doi.org/10.3390/v14081817 - 18 Aug 2022

Cited by 14 | Viewed by 3953

Abstract

As of July 2022, more than 16,000 laboratory-confirmed monkeypox (MPX) cases have been reported worldwide. Until recently, MPX was a rare viral disease seldom detected outside Africa. MPX virus (MPXV) belongs to the Orthopoxvirus (OPV) genus and is a genetically close relative of [...] Read more.

As of July 2022, more than 16,000 laboratory-confirmed monkeypox (MPX) cases have been reported worldwide. Until recently, MPX was a rare viral disease seldom detected outside Africa. MPX virus (MPXV) belongs to the Orthopoxvirus (OPV) genus and is a genetically close relative of the Variola virus (the causative agent of smallpox). Following the eradication of smallpox, there was a significant decrease in smallpox-related morbidity and the population’s immunity to other OPV-related diseases such as MPX. In parallel, there was a need for differential diagnosis between the different OPVs’ clinical manifestations and diseases with similar symptoms (i.e., chickenpox, herpes simplex). The current study aimed to provide a rapid genetic-based diagnostic tool for accurate and specific identification of MPXV and additional related vesicle-forming pathogens. We initially assembled a list of 14 relevant viral pathogens, causing infectious diseases associated with vesicles, prone to be misdiagnosed as MPX. Next, we developed an approach that we termed rapid amplicon nanopore sequencing (RANS). The RANS approach uses diagnostic regions that harbor high homology in their boundaries and internal diagnostic SNPs that, when sequenced, aid the discrimination of each pathogen within a group. During a multiplex PCR amplification, a dA tail and a 5′-phosphonate were simultaneously added, thus making the PCR product ligation ready for nanopore sequencing. Following rapid sequencing (a few minutes), the reads were compared to a reference database and the nearest strain was identified. We first tested our approach using samples of known viruses cultured in cell lines. All the samples were identified correctly and swiftly. Next, we examined a variety of clinical samples from the 2022 MPX outbreak. Our RANS approach identified correctly all the PCR-positive MPXV samples and mapped them to strains that were sequenced during the 2022 outbreak. For the subset of samples that were negative for MPXV by PCR, we obtained definite results, identifying other vesicle-forming viruses: Human herpesvirus 3, Human herpesvirus 2, and Molluscum contagiosum virus. This work was a proof-of-concept study, demonstrating the potential of the RANS approach for rapid and discriminatory identification of a panel of closely related pathogens. The simplicity and affordability of our approach makes it straightforward to implement in any genetics lab. Moreover, other differential diagnostics panels might benefit from the implementation of the RANS approach into their diagnostics pipelines. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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16 pages, 1559 KiB

Open AccessArticle

Effect of Monkeypox Virus Preparation on the Lethality of the Intravenous Cynomolgus Macaque Model

by Eric M. Mucker, Josh D. Shamblin, Jo Lynne Raymond, Nancy A. Twenhafel, Robert F. Garry and Lisa E. Hensley

Viruses 2022, 14(8), 1741; https://doi.org/10.3390/v14081741 - 9 Aug 2022

Cited by 12 | Viewed by 4717

Abstract

For over two decades, researchers have sought to improve smallpox vaccines and also develop therapies to ensure protection against smallpox or smallpox-like disease. The 2022 human monkeypox pandemic is a reminder that these efforts should persist. Advancing such therapies have involved animal models [...] Read more.

For over two decades, researchers have sought to improve smallpox vaccines and also develop therapies to ensure protection against smallpox or smallpox-like disease. The 2022 human monkeypox pandemic is a reminder that these efforts should persist. Advancing such therapies have involved animal models primarily using surrogate viruses such as monkeypox virus. The intravenous monkeypox model in macaques produces a disease that is clinically similar to the lesional phase of fulminant human monkeypox or smallpox. Two criticisms of the model have been the unnatural route of virus administration and the high dose required to induce severe disease. Here, we purified monkeypox virus with the goal of lowering the challenge dose by removing cellular and viral contaminants within the inoculum. We found that there are advantages to using unpurified material for intravenous exposures. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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Review

Jump to: Research, Other

22 pages, 1274 KiB

Open AccessReview

Recent Advances in Research and Management of Human Monkeypox Virus: An Emerging Global Health Threat

by Parveen Kumar, Benu Chaudhary, Nishant Yadav, Sushma Devi, Ashutosh Pareek, Sujatha Alla, Fnu Kajal, Behdin Nowrouzi-Kia, Vijay Kumar Chattu and Madan Mohan Gupta

Viruses 2023, 15(4), 937; https://doi.org/10.3390/v15040937 - 10 Apr 2023

Cited by 8 | Viewed by 4778

Abstract

In 2003, the United States saw an epidemic of monkeypox that was later traced back to rodents of West Africa infected with the monkeypox virus (MPXV). Disease in the United States seemed less severe than the smallpox-like disease in the Democratic Republic of [...] Read more.

In 2003, the United States saw an epidemic of monkeypox that was later traced back to rodents of West Africa infected with the monkeypox virus (MPXV). Disease in the United States seemed less severe than the smallpox-like disease in the Democratic Republic of the Congo (DRC). In this study, researchers analyzed data from Central Africa: two distinct MPXV clades were confirmed by sequencing the genomes of MPXV isolates from Western Africa, the United States, and Central Africa. By comparing open reading frames across MPXV clades, scientists can infer which virus proteins might account for the observed variation in pathogenicity in humans. Monkeypox can be prevented and controlled with a better understanding of MPXV’s molecular etiology and epidemiological and clinical features. In light of the current outbreaks worldwide, we provide updated information on monkeypox for medical professionals in this review. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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8 pages, 753 KiB

Open AccessReview

Reassessment of Evidence about Coinfection of Chickenpox and Monkeypox (Mpox) in African Children

by Ola Khallafallah and Charles Grose

Viruses 2022, 14(12), 2800; https://doi.org/10.3390/v14122800 - 15 Dec 2022

Cited by 14 | Viewed by 4896

Abstract

In west and central Africa, monkeypox occurs mainly in older children, adolescents and young adults. In two large epidemiology studies of monkeypox outbreaks, the investigators observed a sizable number of coinfections of chickenpox (varicella) and monkeypox. Based on a review of the literature, [...] Read more.

In west and central Africa, monkeypox occurs mainly in older children, adolescents and young adults. In two large epidemiology studies of monkeypox outbreaks, the investigators observed a sizable number of coinfections of chickenpox (varicella) and monkeypox. Based on a review of the literature, we propose that chickenpox (human herpesvirus-3 infection) is a risk factor for acquisition of monkeypox infection. Our hypothesis states that the chickenpox skin lesion provides an entry site for the monkeypox virus, which is harbored on a fomite in the environment of the patient. The fact that monkeypox can enter via a scratch or abrasion is a known mechanism of spread for three other poxviruses, including mousepox (ectromelia), orf and molluscum contagiosum. There are many similarities in pathogenesis between certain poxviruses and chickenpox, including a viremia with a cellular stress response leading to high levels of the IL-6 cytokine. One very revealing observation in the two epidemiology studies was that the number of pox as well as the severity of disease in children with chickenpox and monkeypox coinfection was not greater than found in children with monkeypox alone. Based on the above observations, we conclude that, when chickenpox precedes monkeypox, priming of the immune system by the earlier chickenpox infection moderates the severity of the secondary infection with monkeypox. This conclusion also has important public health implications about chickenpox surveillance. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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13 pages, 507 KiB

Open AccessReview

Monkeypox, a Literature Review: What Is New and Where Does This concerning Virus Come From?

by Giorgio Tiecco, Melania Degli Antoni, Samuele Storti, Lina Rachele Tomasoni, Francesco Castelli and Eugenia Quiros-Roldan

Viruses 2022, 14(9), 1894; https://doi.org/10.3390/v14091894 - 27 Aug 2022

Cited by 53 | Viewed by 7683

Abstract

Among the Poxviridae family, orthopoxvirus is the most notorious genus. Several DNA viruses belonging to this group are known to produce human disease from the life-threatening variola virus (VARV) (the causative agent of smallpox), monkeypox virus (MPXV), cowpox virus (CPXV), and vaccinia virus [...] Read more.

Among the Poxviridae family, orthopoxvirus is the most notorious genus. Several DNA viruses belonging to this group are known to produce human disease from the life-threatening variola virus (VARV) (the causative agent of smallpox), monkeypox virus (MPXV), cowpox virus (CPXV), and vaccinia virus (VACV). These orthopoxviruses still remain a public health concern as VACV or CPXV still cause emerging endemic threads, especially in developing countries. MPXV is able to cause sporadic human outbreaks of a smallpox-like zoonotic disease and, in May 2022, hundreds of cases related to MPXV have been reported from more than 30 countries around the globe. At the end of July, monkeypox (MPX) outbreak was even declared a global health emergency by the World Health Organization (WHO). Many aspects remain unclear regarding this outbreak and a deep understanding of orthopoxvirus might have crucial and evident implications. During the era in which people under 45 years old are not protected against VACV, the potential use of orthopoxviruses as a biological weapon raises global concern considering the rapid spreading of the current MPX outbreak in vulnerable populations. Hence, we review the most recent evidence about phylogenesis, pathogenesis, prevention, and treatment for this concerning disease. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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16 pages, 1009 KiB

Open AccessReview

A Glance at the Development and Patent Literature of Tecovirimat: The First-in-Class Therapy for Emerging Monkeypox Outbreak

by Mazen Almehmadi, Mamdouh Allahyani, Ahad Amer Alsaiari, Mohammed Kanan Alshammari, Abrar Saleh Alharbi, Khansa Hamza Hussain, Lojain Ibrahim Alsubaihi, Mehnaz Kamal, Shahad Saleh Alotaibi, Atheer Nasser Alotaibi, Afeefah Awaid Aldhafeeri and Mohd Imran

Viruses 2022, 14(9), 1870; https://doi.org/10.3390/v14091870 - 25 Aug 2022

Cited by 31 | Viewed by 5501

Abstract

Monkeypox disease (MPX) is currently considered a global threat after COVID-19. European Medicines Agency (EMA) approved Tecovirimat in capsule dosage form (200 mg) as the first treatment for MPX in January 2022. This article highlights Tecovirimat’s development and patent literature review and is [...] Read more.

Monkeypox disease (MPX) is currently considered a global threat after COVID-19. European Medicines Agency (EMA) approved Tecovirimat in capsule dosage form (200 mg) as the first treatment for MPX in January 2022. This article highlights Tecovirimat’s development and patent literature review and is believed to benefit the scientists working on developing MPX treatments. The literature for Tecovirimat was gathered from the website of SIGA Technologies (developer of Tecovirimat), regulatory agencies (EMA, United States Food and Drug Administration (USFDA), and Health Canada), PubMed, and freely accessible clinical/patent databases. Tecovirimat was first recognized as an anti-orthopoxvirus molecule in 2002 and developed by SIGA Technologies. The USFDA and Health Canada have also recently approved Tecovirimat to treat smallpox in 2018 and 2021, respectively. The efficacy of Tecovirimat was verified in infected non-human primates (monkeys) and rabbits under the USFDA’s Animal Rule. Most clinical studies have been done on Tecovirimat’s safety and pharmacokinetic parameters. The patent literature has revealed inventions related to the capsule, injection, suspension, crystalline forms, amorphous form, and drug combinations (Tecovirimat + cidofovir) and process for preparing Tecovirimat. The authors foresee the off-label use of Tecovirimat in the USA and Canada for MPX and other orthopoxvirus infections. The authors also trust that there is immense scope for developing new Tecovirimat-based treatments (new drug combinations with other antivirals) for orthopoxvirus and other viral diseases. Drug interaction studies and drug resistance studies on Tecovirimat are also recommended. Tecovirimat is believed to handle the current MPX outbreak and is a new hope of biosecurity against smallpox or orthopoxvirus-related bioterrorism attack. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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Other

Jump to: Research, Review

39 pages, 711 KiB

Open AccessSystematic Review

Prevention and Treatment of Monkeypox: A Systematic Review of Preclinical Studies

by Nurizzati Sudarmaji, Nurolaini Kifli, Andi Hermansyah, Siang Fei Yeoh, Bey-Hing Goh and Long Chiau Ming

Viruses 2022, 14(11), 2496; https://doi.org/10.3390/v14112496 - 11 Nov 2022

Cited by 27 | Viewed by 4172

Abstract

The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review research done on preclinical studies focusing on the potential monkeypox treatment and immunization. The presented juxtaposition of efficacy [...] Read more.

The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review research done on preclinical studies focusing on the potential monkeypox treatment and immunization. The presented juxtaposition of efficacy of potential treatments and vaccination that had been tested in preclinical trials could serve as a useful primer of monkeypox virus. The literature identified using key terms such as monkeypox virus or management or vaccine stringed using Boolean operators was systematically reviewed. Pubmed, SCOPUS, Cochrane, and preprint databases were used, and screening was performed in accordance with PRISMA guidelines. A total of 467 results from registered databases and 116 from grey literature databases were screened. Of these results, 72 studies from registered databases and three grey literature studies underwent full-text screening for eligibility. In this systematic review, a total of 27 articles were eligible according to the inclusion criteria and were used. Tecovirimat, known as TPOXX or ST-246, is an antiviral drug indicated for smallpox infection whereas brincidofovir inhibits the viral DNA polymerase after incorporation into viral DNA. The ability of tecovirimat in providing protection to poxvirus-challenged animals from death had been demonstrated in a number of animal studies. Non-inferior with regard to immunogenicity was reported for the live smallpox/monkeypox vaccine compared with a single dose of a licensed live smallpox vaccine. The trial involving the live vaccine showed a geometric mean titre of vaccinia-neutralizing antibodies post two weeks of the second dose of the live smallpox/monkeypox vaccine. Of note, up to the third generation of smallpox vaccines—particularly JYNNEOS and Lc16m8—have been developed as preventive measures for MPXV infection and these vaccines had been demonstrated to have improved safety compared to the earlier generations. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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Open AccessBrief Report

Retrospective Analysis Revealed an April Occurrence of Monkeypox in the Czech Republic

by Martin Chmel, Oldřich Bartoš, Hana Kabíčková, Petr Pajer, Pavla Kubíčková, Iva Novotná, Zofia Bartovská, Milan Zlámal, Anna Burantová, Michal Holub, Helena Jiřincová, Alexander Nagy, Lenka Černíková, Hana Zákoucká and Jiří Dresler

Viruses 2022, 14(8), 1773; https://doi.org/10.3390/v14081773 - 15 Aug 2022

Cited by 7 | Viewed by 4027

Abstract

Herein, we present our findings of an early appearance of the Monkeypox virus in Prague, Czech Republic. A retrospective analysis of biological samples, carried out on the 28th of April, revealed a previously unrecognized case of Monkeypox virus (MPxV) infection. Subsequent data analysis [...] Read more.

Herein, we present our findings of an early appearance of the Monkeypox virus in Prague, Czech Republic. A retrospective analysis of biological samples, carried out on the 28th of April, revealed a previously unrecognized case of Monkeypox virus (MPxV) infection. Subsequent data analysis confirmed that the virus strain belongs to the ongoing outbreak. Combined with clinical and epidemiological investigations, we extended the roots of the current outbreak at least back to 16th of April, 2022. Full article

(This article belongs to the Special Issue Monkeypox Virus (Mpox))

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