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Nikitin VN, Merkuleva IA, Shcherbakov DN. Monoclonal Antibodies in Light of Mpox Outbreak: Current Research, Therapeutic Targets, and Animal Models. Antibodies (Basel) 2025; 14:20. [PMID: 40136469 PMCID: PMC11939467 DOI: 10.3390/antib14010020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 02/19/2025] [Accepted: 02/21/2025] [Indexed: 03/27/2025] Open
Abstract
The rapid rise in monkeypox virus infections among humans from 2022 to 2024 has captured the attention of the global healthcare community. In light of the lack of mandatory vaccination and limited data on next-generation vaccines for monkeypox prevention, the urgent development of therapeutic agents has become a priority. One promising approach involves the use of neutralizing monoclonal antibodies. This review highlights significant advancements in the search for antibodies against human pathogenic orthopoxviruses, particularly focusing on their potential application against the monkeypox virus. We also analyze viral proteins that serve as targets for identifying therapeutic antibodies capable of neutralizing a wide range of viruses. Finally, we deemed it essential to address the challenges associated with selecting an animal model that can adequately reflect the infectious process of each orthopoxvirus species in humans.
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Affiliation(s)
| | - Iuliia A. Merkuleva
- State Research Center of Virology and Biotechnology Vector, Rospotrebnadzor, Koltsovo 630559, Russia; (V.N.N.); (D.N.S.)
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2
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Omatola CA, Ogunsakin RE, Olaniran AO, Kumari S. Monkeypox Virus Occurrence in Wastewater Environment and Its Correlation with Incidence Cases of Mpox: A Systematic Review and Meta-Analytic Study. Viruses 2025; 17:308. [PMID: 40143239 PMCID: PMC11945618 DOI: 10.3390/v17030308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/18/2025] [Accepted: 02/21/2025] [Indexed: 03/28/2025] Open
Abstract
The COVID-19 pandemic has increased the interest in the use of wastewater-based surveillance (WBS) strategy for infectious disease monitoring, especially when clinical cases are underreported. The excretion of monkey virus (MPXV) in the feces of both symptomatic and preclinical individuals has further driven the interest in WBS applicability to MPXV monitoring in wastewater to support its mitigation efforts. We performed a systematic review with meta-analysis, using six databases to assess MPXV detection in wastewater. We performed a random-effects model meta-analysis to calculate the pooled prevalence at a 95% confidence interval (95% CI). Also, we carried out a subgroup analysis according to the country regions and a sensitivity analysis excluding studies classified as having a high risk of bias. The overall MPXV positivity rate in wastewater was estimated at 22% (95% CI: 14-30%; I2 = 94.8%), with more detection rate in North America (26%, 95% CI: 8-43%) compared to Europe and Asia (22%, 95% CI: 12-31%). The MPXV detection rate was significantly higher in 2022 studies (22%, 95% CI: 13-31%) compared to 2023 (19%, 95% CI: 14-25%). The real-time PCR platform significantly detected more MPXV (24%, 95% CI: 14-34%) than the digital droplet PCR-based studies (17%, 95% CI: 4-31%), which was used less frequently. Viral concentration with centrifugation procedure indicated higher detection rates (21%, 95% CI: 10-33%) than other known sample concentration protocols. Generally, MPXV detection rates in wastewater samples strongly correlate with incidence cases of mpox (range of R = 0.78-0.94; p < 0.05). Findings from this study suggest that WBS of MPXV could be employed as an epidemiological early warning tool for disease monitoring and mpox outbreak prediction similar to the clinical case-based surveillance strategies.
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Affiliation(s)
- Cornelius A. Omatola
- Institute for Water and Wastewater Technology, Durban University of Technology, P.O. Box 1334, Durban 4000, South Africa;
- Department of Microbiology, Kogi State University, Anyigba 272102, Nigeria
| | - Ropo E. Ogunsakin
- School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria 0084, South Africa;
| | - Ademola O. Olaniran
- Discipline of Microbiology, School of Life Sciences, College of Agriculture, Engineering and Science, Westville Campus, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa
| | - Sheena Kumari
- Institute for Water and Wastewater Technology, Durban University of Technology, P.O. Box 1334, Durban 4000, South Africa;
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3
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Alvarez-de Miranda FJ, Martín R, Alcamí A, Hernáez B. Fluorescent Clade IIb Lineage B.1 Mpox Viruses for Antiviral Screening. Viruses 2025; 17:253. [PMID: 40007008 PMCID: PMC11861617 DOI: 10.3390/v17020253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/10/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
The ongoing global outbreak of mpox caused by clade IIb viruses has led to more than 100,000 confirmed cases around the world, highlighting the urgent need for antiviral research to combat current and future mpox outbreaks. Reporter viruses expressing fluorescent proteins to monitor viral replication and virus spreading in cell culture provide a powerful tool for antiviral drug screening. In this work, we engineered two recombinant mpox clade IIb viruses by inserting, under the control of the vaccinia early/late promoter 7.5, the coding sequence of two different fluorescent proteins (EGFP and TurboFP635) in a previously unreported location within the viral genome. These recombinant viruses replicate in BSC-1 cells at rates similar to those of the parental virus. We show how these reporter mpox viruses allow the discrimination of infected cells by cell flow cytometry and facilitate the quantification of viral spread in cell culture. Finally, we validated these reporter viruses with two previously known inhibitors of poxvirus replication, cytosine arabinoside (AraC) and bisbenzimide.
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Affiliation(s)
| | | | | | - Bruno Hernáez
- Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain
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4
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Otieno JR, Ruis C, Onoja AB, Kuppalli K, Hoxha A, Nitsche A, Brinkmann A, Michel J, Mbala-Kingebeni P, Mukadi-Bamuleka D, Osman MM, Hussein H, Raja MA, Fotsing R, Herring BL, Keita M, Rico JM, Gresh L, Barakat A, Katawera V, Nahapetyan K, Naidoo D, Floto RA, Cunningham J, Van Kerkhove MD, Lewis RF, Subissi L. Global genomic surveillance of monkeypox virus. Nat Med 2025; 31:342-350. [PMID: 39442559 PMCID: PMC11750716 DOI: 10.1038/s41591-024-03370-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 10/21/2024] [Indexed: 11/22/2024]
Abstract
Monkeypox virus (MPXV) is endemic in western and Central Africa, and in May 2022, a clade IIb lineage (B.1) caused a global outbreak outside Africa, resulting in its detection in 116 countries and territories. To understand the global phylogenetics of MPXV, we analyzed all available MPXV sequences, including 10,670 sequences from 65 countries collected between 1958 and 2024. Our analysis reveals high mobility of clade I viruses within Central Africa, sustained human-to-human transmission of clade IIb lineage A viruses within the Eastern Mediterranean region and distinct mutational signatures that can distinguish sustained human-to-human from animal-to-animal transmission. Moreover, distinct clade I sequences from Sudan suggest local MPXV circulation in areas of eastern Africa over the past four decades. Our study underscores the importance of genomic surveillance in tracking spatiotemporal dynamics of MXPV clades and the need to strengthen such surveillance, including in some parts of eastern Africa.
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Affiliation(s)
| | - Christopher Ruis
- World Health Organization, Geneva, Switzerland
- Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK
- Cambridge Centre for AI in Medicine, University of Cambridge, Cambridge, UK
- Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
| | | | - Krutika Kuppalli
- World Health Organization, Geneva, Switzerland
- Department of Medicine, University of Texas Southwestern, Dallas, TX, USA
- Peter O'Donnell Jr School of Public Health, University of Texas Southwestern, Dallas, TX, USA
| | - Ana Hoxha
- World Health Organization, Geneva, Switzerland
| | - Andreas Nitsche
- ZBS-Highly Pathogenic Viruses, German Consultant Laboratory for Poxviruses, WHO Collaborating Centre for Emerging Infections and Biological Threats, Robert Koch Institute, Berlin, Germany
| | - Annika Brinkmann
- ZBS-Highly Pathogenic Viruses, German Consultant Laboratory for Poxviruses, WHO Collaborating Centre for Emerging Infections and Biological Threats, Robert Koch Institute, Berlin, Germany
| | - Janine Michel
- ZBS-Highly Pathogenic Viruses, German Consultant Laboratory for Poxviruses, WHO Collaborating Centre for Emerging Infections and Biological Threats, Robert Koch Institute, Berlin, Germany
| | - Placide Mbala-Kingebeni
- National Institute for Biomedical Research, Kinshasa, Democratic Republic of the Congo
- University of Kinshasa, Kinshasa, Democratic Republic of the Congo
| | - Daniel Mukadi-Bamuleka
- University of Kinshasa, Kinshasa, Democratic Republic of the Congo
- National Institute for Biomedical Research, Goma, Democratic Republic of the Congo
| | - Muntasir Mohammed Osman
- Health Emergencies and Epidemics Control, Federal Ministry of Health, Khartoum, Republic of the Sudan
| | - Hanadi Hussein
- Health Emergencies and Epidemics Control, Federal Ministry of Health, Khartoum, Republic of the Sudan
| | - Muhammad Ali Raja
- World Health Organization Country Office, Port Sudan, Republic of the Sudan
| | - Richard Fotsing
- World Health Organization Country Office, Kinshasa, Democratic Republic of the Congo
| | - Belinda L Herring
- World Health Organization Regional Office for Africa, Brazzaville, Republic of the Congo
| | - Mory Keita
- World Health Organization Regional Office for Africa, Brazzaville, Republic of the Congo
| | - Jairo Mendez Rico
- World Health Organization Regional Office for the Americas, Washington DC, USA
| | - Lionel Gresh
- World Health Organization Regional Office for the Americas, Washington DC, USA
| | - Amal Barakat
- World Health Organization Regional Office for the Eastern Mediterranean, Cairo, Egypt
| | - Victoria Katawera
- World Health Organization Regional Office for the Western Pacific, Manila, Philippines
| | - Karen Nahapetyan
- World Health Organization Regional Office for Europe, Copenhagen, Denmark
| | - Dhamari Naidoo
- World Health Organization Regional Office for South-East Asia, New Delhi, India
| | - R Andres Floto
- Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK
- Cambridge Centre for AI in Medicine, University of Cambridge, Cambridge, UK
- Cambridge Centre for Lung Infection, Papworth Hospital, Cambridge, UK
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5
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Mantlo E, Trujillo JD, Gaudreault NN, Morozov I, Lewis CE, Matias-Ferreyra F, McDowell C, Bold D, Kwon T, Cool K, Balaraman V, Madden D, Artiaga B, Souza-Neto J, Doty JB, Carossino M, Balasuriya U, Wilson WC, Osterrieder N, Hensley L, Richt JA. Experimental inoculation of pigs with monkeypox virus results in productive infection and transmission to sentinels. Emerg Microbes Infect 2024; 13:2352434. [PMID: 38712637 PMCID: PMC11168330 DOI: 10.1080/22221751.2024.2352434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 05/02/2024] [Indexed: 05/08/2024]
Abstract
Monkeypox virus (MPXV) is a re-emerging zoonotic poxvirus responsible for producing skin lesions in humans. Endemic in sub-Saharan Africa, the 2022 outbreak with a clade IIb strain has resulted in ongoing sustained transmission of the virus worldwide. MPXV has a relatively wide host range, with infections reported in rodent and non-human primate species. However, the susceptibility of many domestic livestock species remains unknown. Here, we report on a susceptibility/transmission study in domestic pigs that were experimentally inoculated with a 2022 MPXV clade IIb isolate or served as sentinel contact control animals. Several principal-infected and sentinel contact control pigs developed minor lesions near the lips and nose starting at 12 through 18 days post-challenge (DPC). No virus was isolated and no viral DNA was detected from the lesions; however, MPXV antigen was detected by IHC in tissue from a pustule of a principal infected pig. Viral DNA and infectious virus were detected in nasal and oral swabs up to 14 DPC, with peak titers observed at 7 DPC. Viral DNA was also detected in nasal tissues or skin collected from two principal-infected animals at 7 DPC post-mortem. Furthermore, all principal-infected and sentinel control animals enrolled in the study seroconverted. In conclusion, we provide the first evidence that domestic pigs are susceptible to experimental MPXV infection and can transmit the virus to contact animals.
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Affiliation(s)
- Emily Mantlo
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Jessie D. Trujillo
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Natasha N. Gaudreault
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Igor Morozov
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Charles E. Lewis
- Foreign Animal Disease Diagnostic Laboratory, National Bio and Agro-defense Facility, Animal and Plant Health Inspection Service, United States Department of Agriculture, Manhattan, KS, USA
| | - Franco Matias-Ferreyra
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Chester McDowell
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Dashzeveg Bold
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Taeyong Kwon
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Konner Cool
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Velmurugan Balaraman
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Daniel Madden
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Bianca Artiaga
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Jayme Souza-Neto
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Jeffrey B. Doty
- U.S. Centers for Disease Control and Prevention, Poxvirus and Rabies Branch, Atlanta, GA, USA
| | - Mariano Carossino
- Louisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA
| | - Udeni Balasuriya
- Louisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA
| | - William C. Wilson
- Foreign Arthropod-Borne Animal Diseases Research Unit, National Bio and Agro-defense Facility, Agricultural Research Service, United States Department of Agriculture, Manhattan, KS, USA
| | - Nikolaus Osterrieder
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
| | - Lisa Hensley
- Zoonotic and Emerging Disease Research Unit, National Bio- and Agro-defense Facility, Agricultural Research Service, United States Department of Agriculture, Manhattan, KS, USA
| | - Juergen A. Richt
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
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6
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Pierron M, Sueur C, Shimada M, MacIntosh AJJ, Romano V. Epidemiological Consequences of Individual Centrality on Wild Chimpanzees. Am J Primatol 2024; 86:e23682. [PMID: 39245992 DOI: 10.1002/ajp.23682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 08/14/2024] [Accepted: 08/20/2024] [Indexed: 09/10/2024]
Abstract
Disease outbreaks are one of the key threats to great apes and other wildlife. Because the spread of some pathogens (e.g., respiratory viruses, sexually transmitted diseases, ectoparasites) are mediated by social interactions, there is a growing interest in understanding how social networks predict the chain of pathogen transmission. In this study, we built a party network from wild chimpanzees (Pan troglodytes), and used agent-based modeling to test: (i) whether individual attributes (sex, age) predict individual centrality (i.e., whether it is more or less socially connected); (ii) whether individual centrality affects an individual's role in the chain of pathogen transmission; and, (iii) whether the basic reproduction number (R0) and infectious period modulate the influence of centrality on pathogen transmission. We show that sex and age predict individual centrality, with older males presenting many (degree centrality) and strong (strength centrality) relationships. As expected, males are more central than females within their network, and their centrality determines their probability of getting infected during simulated outbreaks. We then demonstrate that direct measures of social interaction (strength centrality), as well as eigenvector centrality, strongly predict disease dynamics in the chimpanzee community. Finally, we show that this predictive power depends on the pathogen's R0 and infectious period: individual centrality was most predictive in simulations with the most transmissible pathogens and long-lasting diseases. These findings highlight the importance of considering animal social networks when investigating disease outbreaks.
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Affiliation(s)
- Maxime Pierron
- Département de Biologie, Faculté des Sciences et Technologies, Université de Lille, Lille, France
| | - Cédric Sueur
- IPHC UMR 7178, CNRS, Université de Strasbourg, Strasbourg, France
- Institut Universitaire de France, Paris, France
- Anthropo-Lab, ETHICS EA7446, Lille Catholic University, Lille, France
| | - Masaki Shimada
- Department of Animal Sciences, Teikyo University of Science, Uenohara, Yamanashi, Japan
| | | | - Valéria Romano
- IPHC UMR 7178, CNRS, Université de Strasbourg, Strasbourg, France
- Wildlife Research Center, Kyoto University, Inuyama, Japan
- IMBE, Aix Marseille University, Avignon University, CNRS, IRD, Marseille, France
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7
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Derhab N. Human monkeypox virus: A systematic critical review during the pandemic peak. Indian J Med Microbiol 2024; 51:100704. [PMID: 39134221 DOI: 10.1016/j.ijmmb.2024.100704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 08/05/2024] [Accepted: 08/10/2024] [Indexed: 08/17/2024]
Abstract
BACKGROUND In July 2022, the world health organization (WHO) announced the monkeypox virus (MPXV) as a public health emergency of international concern, due to the unprecedented global transmission of the disease beyond previously endemic countries in Africa. METHODS For this systematic review, the author searched the "web of science" (WoS) database, which retrieves 138 articles on MPXV, published between 01-04-2022 and 22-09-2022. This period witnessed the maximum cases of infection as confirmed by the WHO. Seventy articles were used for in-depth analysis, after excluding papers not highly relevant to the topic. RESULTS AND CONCLUSIONS The current review demonstrates different types of MPXV identification analysis, transmission of MPXV, clinical features, immune responses against MPXV, the mutations, and phylogenetic analysis. It also identifies the patients with high-risk complications and determines the other diseases related to MPXV. This paper provides suggestions for the suitable usage of vaccines or antiviral drugs as a procedure to control the outbreak and preventive strategies related to the humans. This research discusses significant implications and recommendations to contribute in reducing the spread of MPXV and presents avenues for upcoming MPXV research.
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Affiliation(s)
- Neama Derhab
- Department of Botany and Microbiology, Faculty of Science, Damanhour University, Damanhour, Egypt.
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8
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Xu J, Liu C, Zhang Q, Zhu H, Cui F, Zhao Z, Song M, Zhou B, Zhang Y, Hu P, Li L, Wang Q, Wang P. The first detection of mpox virus DNA from wastewater in China. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 932:172742. [PMID: 38679098 DOI: 10.1016/j.scitotenv.2024.172742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 04/14/2024] [Accepted: 04/22/2024] [Indexed: 05/01/2024]
Abstract
Wastewater monitoring may be a valuable early surveillance tool for studying mpox virus (MPXV) circulation in China, a country with high population density and very few mpox patients. To evaluate the effectiveness of wastewater monitoring for MPXV in detecting local hidden transmission of the epidemic in the early period, the Chinese Center for Disease Control and Prevention initiated a wastewater monitoring program for MPXV in China in July 2023. To enhance the monitoring sensitivity of the program, an MPXV monitoring point was established in a gathering place of high-risk mpox population. Three different concentration methods, PEG precipitation, ultrafiltration, and magnetic beads method were evaluated and compared. Due to its high recovery efficiency, low limit of detection, and high degree of automation, the magnetic beads method was selected for the daily surveillance of MPXV in wastewater. On September 5, 2023, MPXV DNA was detected at the MPXV monitoring point in Zibo City, marking the first instance of MPXV detection of MPXV in wastewater in China. Next-generation sequencing was conducted on the MPXV genome obtained from the positive wastewater, positive environmental samples, and the single case of mpox in Zibo in September. The results showed that the genotypes of these three genomes were different but all belong to the IIb branch of the C.1 lineage, indicating a probably hidden transmission of mpox. Wastewater monitoring is potentially an effective early surveillance tool for tracking the spread of MPXV in areas with high population density and very few mpox patients.
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Affiliation(s)
- Jin Xu
- Center for Disease Control and Prevention of Zibo, Zibo 255000, PR China
| | - Chao Liu
- Center for Disease Control and Prevention of Zibo, Zibo 255000, PR China
| | - Qun Zhang
- Center for Disease Control and Prevention of Zibo, Zibo 255000, PR China
| | - Haining Zhu
- Center for Disease Control and Prevention of Zibo, Zibo 255000, PR China
| | - Feng Cui
- Center for Disease Control and Prevention of Zibo, Zibo 255000, PR China
| | - Zhiqiang Zhao
- Center for Disease Control and Prevention of Zibo, Zibo 255000, PR China
| | - Mingfang Song
- Sunan Institute for Molecular Engineering, Peking University, Suzhou 215000, PR China
| | - Bo Zhou
- Sunan Institute for Molecular Engineering, Peking University, Suzhou 215000, PR China
| | - Yunxiao Zhang
- Center for Disease Control and Prevention of Zibo, Zibo 255000, PR China
| | - Peilong Hu
- Center for Disease Control and Prevention of Zibo, Zibo 255000, PR China
| | - Lei Li
- Center for Disease Control and Prevention of Zibo, Zibo 255000, PR China
| | - Qin Wang
- Center for Disease Control and Prevention of Zibo, Zibo 255000, PR China.
| | - Peng Wang
- School of Material Science and Engineering, Shandong University of Technology, Zibo 255000, PR China
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9
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Bonilla-Aldana DK, Bonilla-Aldana JL, Ulloque-Badaracco JR, Al-Kassab-Córdova A, Hernandez-Bustamante EA, Alarcon-Braga EA, Benites-Zapata VA, Copaja-Corzo C, Silva-Cajaleon K, Rodriguez-Morales AJ. Mpox infection in animals: A systematic review and meta-analysis. J Infect Public Health 2024; 17:102431. [PMID: 38820901 DOI: 10.1016/j.jiph.2024.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 03/26/2024] [Accepted: 04/17/2024] [Indexed: 06/02/2024] Open
Abstract
Mpox is a zoonotic disease that became epidemic in multiple countries in 2022. There is a lack of published systematic reviews on natural animal infection due to Mpox. We performed a systematic literature review with meta-analysis to assess animal Mpox prevalence. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI) for prevalence studies. After the screening, 15 reports were selected for full-text assessment and included in qualitative and quantitative analyses. Ten reports assessed Mpox infection by molecular or serological tests (n = 2680), yielding a pooled prevalence of 16.0% (95%CI: 3.0-29.0%) for non-human primates; 8.0% (95%CI: 4.0-12.0%) for rodents and 1.0% (95%CI: 0.0-3.0%) for shrews. Further studies in other animals are required to define the extent and importance of natural infection due to Mpox. These findings have implications for public human and animal health. OneHealth approach is critical for prevention and control.
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Affiliation(s)
| | - Jorge Luis Bonilla-Aldana
- Grupo de Investigación en Ciencias Animales Macagual, Universidad de La Amazonia, Florencia, Caquetá 180002, Colombia
| | | | - Ali Al-Kassab-Córdova
- Centro de Excelencia en Investigaciones Económicas y Sociales en Salud, Universidad San Ignacio de Loyola, Lima 15012, Peru
| | - Enrique A Hernandez-Bustamante
- Grupo Peruano de Investigación Epidemiológica, Unidad para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima 15012, Peru; Sociedad Científica de Estudiantes de Medicina de la Universidad Nacional de Trujillo, Trujillo 13011, Peru
| | | | | | - Cesar Copaja-Corzo
- Unidad de Investigación para la generación y síntesis de evidencias en salud, Universidad San Ignacio de Loyola, Lima 15012, Peru; Servicio de infectología, Hospital Nacional Edgardo Rebagliati Martins, EsSalud, Lima 15072, Peru
| | - Kenneth Silva-Cajaleon
- Faculties of Environmental and Health Sciences, Universidad Científica del Sur, Lima 4861, Peru
| | - Alfonso J Rodriguez-Morales
- Faculties of Environmental and Health Sciences, Universidad Científica del Sur, Lima 4861, Peru; Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de las Américas-Institución Universitaria Visión de las Américas, Pereira, 660003 Risaralda, Colombia; Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon
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10
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Gogarten JF, Düx A, Gräßle T, Lumbu CP, Markert S, Patrono LV, Pléh KA, Singa FN, Tanga CTF, Tombolomako TB, Couacy-Hymann E, Kouadio L, Ahuka-Mundeke S, Makouloutou-Nzassi P, Calvignac-Spencer S, Leendertz FH. An ounce of prevention is better : Monitoring wildlife health as a tool for pandemic prevention. EMBO Rep 2024; 25:2819-2831. [PMID: 38849672 PMCID: PMC11239677 DOI: 10.1038/s44319-024-00156-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 04/30/2024] [Indexed: 06/09/2024] Open
Abstract
Long-term observations of wildlife are key to understanding the ecological foundations of disease emergence. They provide unique opportunities to detect pathogens with zoonotic potential that could threaten human health but also pose a threat for the animals.
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Affiliation(s)
- Jan Frederik Gogarten
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany
- Department of Applied Zoology and Nature Conservation, University of Greifswald, Greifswald, Germany
| | - Ariane Düx
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany
- Taï Chimpanzee Project, Centre Suisse de Recherches Scientifiques, Abidjan, Côte d'Ivoire
| | - Tobias Gräßle
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany
| | - Christelle Patricia Lumbu
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany
- Institut National de Recherche Biomedical, Kinshasa, Democratic Republic of the Congo
- Kokolopori Bonobo Research Project, Tshuapa, Democratic Republic of the Congo
| | - Stephanie Markert
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany
| | - Livia Victoria Patrono
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany
| | - Kamilla Anna Pléh
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany
- Taï Chimpanzee Project, Centre Suisse de Recherches Scientifiques, Abidjan, Côte d'Ivoire
| | - Frederic Niatou Singa
- WWF Central African Republic Programme Office, Dzanga Sangha Protected Areas, Bangui, Central African Republic
| | - Coch Tanguy Floyde Tanga
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany
- Institut de Recherche en Ecologie Tropicale, Libreville, Gabon
- Ozouga Chimpanzee Project, Loango National Park, Gabon
- Loango Gorilla Project, Loango National Park, Gabon
| | - Thais Berenger Tombolomako
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany
- WWF Central African Republic Programme Office, Dzanga Sangha Protected Areas, Bangui, Central African Republic
| | | | - Leonce Kouadio
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany
- Université Peleforo Gon Coulibaly, Korhogo, Côte d'Ivoire
- Centre Suisse de Recherches Scientifiques, Abidjan, Côte d'Ivoire
| | - Steve Ahuka-Mundeke
- Service de Microbiologie, Departement de Biologie Médicale, Cliniques Universitaires de Kinshasa (CUK), Université de Kinshasa (UNIKIN), Kinshasa, Democratic Republic of the Congo
- Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo
| | - Patrice Makouloutou-Nzassi
- Département de Biologie et Écologie Animale, Institut de Recherche en Écologie Tropicale (IRET/CENAREST), Libreville, Gabon
- Unité de Recherche en Écologie de la Santé, CIRMF, Franceville, Gabon
| | - Sébastien Calvignac-Spencer
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany
- Faculty of Mathematics and Natural Sciences, University of Greifswald, Greifswald, Germany
| | - Fabian Hubertus Leendertz
- Helmholtz Institute for One Health, Helmholtz-Centre for Infection Research (HZI), Greifswald, Germany.
- Taï Chimpanzee Project, Centre Suisse de Recherches Scientifiques, Abidjan, Côte d'Ivoire.
- Faculty of Mathematics and Natural Sciences, University of Greifswald, Greifswald, Germany.
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11
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Djuicy DD, Omah IF, Parker E, Tomkins-Tinch CH, Otieno JR, Yifomnjou MHM, Essengue LLM, Ayinla AO, Sijuwola AE, Ahmed MI, Ope-ewe OO, Ogunsanya OA, Olono A, Eromon P, Yonga MGW, Essima GD, Touoyem IP, Mounchili LJM, Eyangoh SI, Esso L, Nguidjol IME, Metomb SF, Chebo C, Agwe SM, Mossi HM, Bilounga CN, Etoundi AGM, Akanbi O, Egwuenu A, Ehiakhamen O, Chukwu C, Suleiman K, Akinpelu A, Ahmad A, Imam KI, Ojedele R, Oripenaye V, Ikeata K, Adelakun S, Olajumoke B, O’Toole Á, Magee A, Zeller M, Gangavarapu K, Varilly P, Park DJ, Mboowa G, Tessema SK, Tebeje YK, Folarin O, Happi A, Lemey P, Suchard MA, Andersen KG, Sabeti P, Rambaut A, Ihekweazu C, Jide I, Adetifa I, Njoum R, Happi CT. Molecular epidemiology of recurrent zoonotic transmission of mpox virus in West Africa. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.06.18.24309115. [PMID: 38947021 PMCID: PMC11213044 DOI: 10.1101/2024.06.18.24309115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Nigeria and Cameroon reported their first mpox cases in over three decades in 2017 and 2018 respectively. The outbreak in Nigeria is recognised as an ongoing human epidemic. However, owing to sparse surveillance and genomic data, it is not known whether the increase in cases in Cameroon is driven by zoonotic or sustained human transmission. Notably, the frequency of zoonotic transmission remains unknown in both Cameroon and Nigeria. To address these uncertainties, we investigated the zoonotic transmission dynamics of the mpox virus (MPXV) in Cameroon and Nigeria, with a particular focus on the border regions. We show that in these regions mpox cases are still driven by zoonotic transmission of a newly identified Clade IIb.1. We identify two distinct zoonotic lineages that circulate across the Nigeria-Cameroon border, with evidence of recent and historic cross border dissemination. Our findings support that the complex cross-border forest ecosystems likely hosts shared animal populations that drive cross-border viral spread, which is likely where extant Clade IIb originated. We identify that the closest zoonotic outgroup to the human epidemic circulated in southern Nigeria in October 2013. We also show that the zoonotic precursor lineage circulated in an animal population in southern Nigeria for more than 45 years. This supports findings that southern Nigeria was the origin of the human epidemic. Our study highlights the ongoing MPXV zoonotic transmission in Cameroon and Nigeria, underscoring the continuous risk of MPXV (re)emergence.
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Affiliation(s)
- Delia Doreen Djuicy
- Virology Service, Centre Pasteur du Cameroun, 451 Rue 2005, Yaounde 2, P.O. Box 1274
| | - Ifeanyi F. Omah
- Institute of Ecology and Evolution, University of Edinburgh, The King’s Buildings, Edinburgh EH9 3FL, UK
- Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka, Nigeria
| | - Edyth Parker
- African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeria
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
| | | | | | | | | | - Akeemat Opeyemi Ayinla
- African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeria
| | - Ayotunde E. Sijuwola
- African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeria
| | - Muhammad I. Ahmed
- African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeria
| | - Oludayo O. Ope-ewe
- African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeria
| | - Olusola Akinola Ogunsanya
- African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeria
| | - Alhaji Olono
- African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeria
| | - Philomena Eromon
- African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeria
| | | | - Gael Dieudonné Essima
- Virology Service, Centre Pasteur du Cameroun, 451 Rue 2005, Yaounde 2, P.O. Box 1274
| | | | | | - Sara Irene Eyangoh
- Virology Service, Centre Pasteur du Cameroun, 451 Rue 2005, Yaounde 2, P.O. Box 1274
| | - Linda Esso
- Department for the Control of Disease, Epidemics and Pandemics, Ministry of Public Health, Yaounde, Cameroon
| | - Inès Mandah Emah Nguidjol
- Department for the Control of Disease, Epidemics and Pandemics, Ministry of Public Health, Yaounde, Cameroon
| | - Steve Franck Metomb
- Department for the Control of Disease, Epidemics and Pandemics, Ministry of Public Health, Yaounde, Cameroon
| | - Cornelius Chebo
- Department for the Control of Disease, Epidemics and Pandemics, Ministry of Public Health, Yaounde, Cameroon
| | - Samuel Mbah Agwe
- Department for the Control of Disease, Epidemics and Pandemics, Ministry of Public Health, Yaounde, Cameroon
| | - Hans Makembe Mossi
- Department for the Control of Disease, Epidemics and Pandemics, Ministry of Public Health, Yaounde, Cameroon
| | - Chanceline Ndongo Bilounga
- Department for the Control of Disease, Epidemics and Pandemics, Ministry of Public Health, Yaounde, Cameroon
| | | | - Olusola Akanbi
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | - Abiodun Egwuenu
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | | | - Chimaobi Chukwu
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | - Kabiru Suleiman
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | - Afolabi Akinpelu
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | - Adama Ahmad
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | | | - Richard Ojedele
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | - Victor Oripenaye
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | - Kenneth Ikeata
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | | | | | - Áine O’Toole
- Institute of Ecology and Evolution, University of Edinburgh, The King’s Buildings, Edinburgh EH9 3FL, UK
| | - Andrew Magee
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Mark Zeller
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
| | - Karthik Gangavarapu
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
| | - Patrick Varilly
- The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Daniel J Park
- The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Gerald Mboowa
- Africa Centres for Disease Control and Prevention (Africa CDC),Addis Ababa, Ethiopia
| | | | - Yenew Kebede Tebeje
- Africa Centres for Disease Control and Prevention (Africa CDC),Addis Ababa, Ethiopia
| | - Onikepe Folarin
- African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeria
- Department of Biological Sciences, Redeemer’s University, Ede, Osun State, Nigeria
| | - Anise Happi
- African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeria
| | - Philippe Lemey
- Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium
| | - Marc A Suchard
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Department of Biomathematics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Kristian G. Andersen
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
- Scripps Research Translational Institute, La Jolla, CA 92037, USA
| | - Pardis Sabeti
- The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, MA 02115, USA
| | - Andrew Rambaut
- Institute of Ecology and Evolution, University of Edinburgh, The King’s Buildings, Edinburgh EH9 3FL, UK
| | - Chikwe Ihekweazu
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | - Idriss Jide
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | - Ifedayo Adetifa
- Nigeria Centre for Disease Control and Prevention., Abuja, Nigeria
| | - Richard Njoum
- Virology Service, Centre Pasteur du Cameroun, 451 Rue 2005, Yaounde 2, P.O. Box 1274
| | - Christian T Happi
- African Center of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeria
- Department of Biological Sciences, Redeemer’s University, Ede, Osun State, Nigeria
- Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, MA 02115, USA
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12
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Moss B. Understanding the biology of monkeypox virus to prevent future outbreaks. Nat Microbiol 2024; 9:1408-1416. [PMID: 38724757 DOI: 10.1038/s41564-024-01690-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 03/26/2024] [Indexed: 06/07/2024]
Abstract
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.
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Affiliation(s)
- Bernard Moss
- Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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13
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Weary TE, Pappas T, Tusiime P, Tuhaise S, Otali E, Emery Thompson M, Ross E, Gern JE, Goldberg TL. Common cold viruses circulating in children threaten wild chimpanzees through asymptomatic adult carriers. Sci Rep 2024; 14:10431. [PMID: 38714841 PMCID: PMC11076286 DOI: 10.1038/s41598-024-61236-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 05/02/2024] [Indexed: 05/12/2024] Open
Abstract
Reverse zoonotic respiratory diseases threaten great apes across Sub-Saharan Africa. Studies of wild chimpanzees have identified the causative agents of most respiratory disease outbreaks as "common cold" paediatric human pathogens, but reverse zoonotic transmission pathways have remained unclear. Between May 2019 and August 2021, we conducted a prospective cohort study of 234 children aged 3-11 years in communities bordering Kibale National Park, Uganda, and 30 adults who were forest workers and regularly entered the park. We collected 2047 respiratory symptoms surveys to quantify clinical severity and simultaneously collected 1989 nasopharyngeal swabs approximately monthly for multiplex viral diagnostics. Throughout the course of the study, we also collected 445 faecal samples from 55 wild chimpanzees living nearby in Kibale in social groups that have experienced repeated, and sometimes lethal, epidemics of human-origin respiratory viral disease. We characterized respiratory pathogens in each cohort and examined statistical associations between PCR positivity for detected pathogens and potential risk factors. Children exhibited high incidence rates of respiratory infections, whereas incidence rates in adults were far lower. COVID-19 lockdown in 2020-2021 significantly decreased respiratory disease incidence in both people and chimpanzees. Human respiratory infections peaked in June and September, corresponding to when children returned to school. Rhinovirus, which caused a 2013 outbreak that killed 10% of chimpanzees in a Kibale community, was the most prevalent human pathogen throughout the study and the only pathogen present at each monthly sampling, even during COVID-19 lockdown. Rhinovirus was also most likely to be carried asymptomatically by adults. Although we did not detect human respiratory pathogens in the chimpanzees during the cohort study, we detected human metapneumovirus in two chimpanzees from a February 2023 outbreak that were genetically similar to viruses detected in study participants in 2019. Our data suggest that respiratory pathogens circulate in children and that adults become asymptomatically infected during high-transmission times of year. These asymptomatic adults may then unknowingly carry the pathogens into forest and infect chimpanzees. This conclusion, in turn, implies that intervention strategies based on respiratory symptoms in adults are unlikely to be effective for reducing reverse zoonotic transmission of respiratory viruses to chimpanzees.
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Affiliation(s)
- Taylor E Weary
- Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI, USA
| | - Tressa Pappas
- Department of Paediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | | | | | - Emily Otali
- The Kasiisi Project, Fort Portal, Uganda
- Kibale Chimpanzee Project, Fort Portal, Uganda
| | - Melissa Emery Thompson
- Kibale Chimpanzee Project, Fort Portal, Uganda
- Department of Anthropology, University of New Mexico, Albuquerque, NM, USA
| | | | - James E Gern
- Department of Paediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Tony L Goldberg
- Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI, USA.
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14
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Besombes C, Mbrenga F, Gonofio E, Malaka C, Bationo CS, Gaudart J, Curaudeau M, Hassanin A, Gessain A, Duda R, Vernick TG, Fontanet A, Nakouné E, Landier J. Seasonal Patterns of Mpox Index Cases, Africa, 1970-2021. Emerg Infect Dis 2024; 30:1017-1021. [PMID: 38666645 PMCID: PMC11060470 DOI: 10.3201/eid3005.230293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2024] Open
Abstract
Across 133 confirmed mpox zoonotic index cases reported during 1970-2021 in Africa, cases occurred year-round near the equator, where climate is consistent. However, in tropical regions of the northern hemisphere under a dry/wet season cycle, cases occurred seasonally. Our findings further support the seasonality of mpox zoonotic transmission risk.
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15
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Monzón S, Varona S, Negredo A, Vidal-Freire S, Patiño-Galindo JA, Ferressini-Gerpe N, Zaballos A, Orviz E, Ayerdi O, Muñoz-Gómez A, Delgado-Iribarren A, Estrada V, García C, Molero F, Sánchez-Mora P, Torres M, Vázquez A, Galán JC, Torres I, Causse Del Río M, Merino-Diaz L, López M, Galar A, Cardeñoso L, Gutiérrez A, Loras C, Escribano I, Alvarez-Argüelles ME, Del Río L, Simón M, Meléndez MA, Camacho J, Herrero L, Jiménez P, Navarro-Rico ML, Jado I, Giannetti E, Kuhn JH, Sanchez-Lockhart M, Di Paola N, Kugelman JR, Guerra S, García-Sastre A, Cuesta I, Sánchez-Seco MP, Palacios G. Monkeypox virus genomic accordion strategies. Nat Commun 2024; 15:3059. [PMID: 38637500 PMCID: PMC11026394 DOI: 10.1038/s41467-024-46949-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 03/14/2024] [Indexed: 04/20/2024] Open
Abstract
The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.
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Affiliation(s)
- Sara Monzón
- Unidad de Bioinformática, Unidades Centrales Científico Técnicas, Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Sarai Varona
- Unidad de Bioinformática, Unidades Centrales Científico Técnicas, Instituto de Salud Carlos III, 28029, Madrid, Spain
- Escuela Internacional de Doctorado de la UNED (EIDUNED), Universidad Nacional de Educación a Distancia (UNED), 2832, Madrid, Spain
| | - Anabel Negredo
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28029, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Santiago Vidal-Freire
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | | | | | - Angel Zaballos
- Unidad de Genómica, Unidades Centrales Científico Técnicas, Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Eva Orviz
- Centro Sanitario Sandoval, Hospital Clínico San Carlos, 28040, Madrid, Spain
| | - Oskar Ayerdi
- Centro Sanitario Sandoval, Hospital Clínico San Carlos, 28040, Madrid, Spain
| | - Ana Muñoz-Gómez
- Centro Sanitario Sandoval, Hospital Clínico San Carlos, 28040, Madrid, Spain
| | | | - Vicente Estrada
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029, Madrid, Spain
- Centro Sanitario Sandoval, Hospital Clínico San Carlos, 28040, Madrid, Spain
| | - Cristina García
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Francisca Molero
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Patricia Sánchez-Mora
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28029, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Montserrat Torres
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28029, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Ana Vázquez
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28029, Madrid, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Juan-Carlos Galán
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, 28029, Madrid, Spain
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034, Madrid, Spain
| | - Ignacio Torres
- Servicio de Microbiología, Hospital Clínico Universitario, Instituto de Investigación INCLIVA, 46010, Valencia, Spain
| | - Manuel Causse Del Río
- Unidad de Microbiología, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba, 14004, Córdoba, Spain
| | - Laura Merino-Diaz
- Unidad Clínico de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, 41013, Sevilla, Spain
| | - Marcos López
- Servicio de Microbiología y Parasitología, Hospital Universitario Puerta de Hierro Majadahonda, 28222, Madrid, Spain
| | - Alicia Galar
- Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, 28007, Madrid, Spain
| | - Laura Cardeñoso
- Servicio de Microbiología, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, 28006, Madrid, Spain
| | - Almudena Gutiérrez
- Servicio de Microbiología y Parasitología Clínica, Hospital Universitario La Paz, 28046, Madrid, Spain
| | - Cristina Loras
- Servicio de Microbiología, Hospital General y Universitario, 13005, Ciudad Real, Spain
| | - Isabel Escribano
- Servicio de Microbiología, Hospital General Universitario Dr. Balmis, 03010, Alicante, Spain
| | | | | | - María Simón
- Servicio de Microbiología, Hospital Central de la Defensa "Gómez Ulla", 28947, Madrid, Spain
| | - María Angeles Meléndez
- Servicio de Microbiología y Parasitología, Hospital Universitario 12 de Octubre, 28041, Madrid, Spain
| | - Juan Camacho
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Laura Herrero
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28029, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Pilar Jiménez
- Unidad de Genómica, Unidades Centrales Científico Técnicas, Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - María Luisa Navarro-Rico
- Unidad de Genómica, Unidades Centrales Científico Técnicas, Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Isabel Jado
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Elaina Giannetti
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Jens H Kuhn
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, 21702, USA
| | - Mariano Sanchez-Lockhart
- United States Army Research Institute for Infectious Disease, Fort Detrick, Frederick, MD, 21702, USA
| | - Nicholas Di Paola
- United States Army Research Institute for Infectious Disease, Fort Detrick, Frederick, MD, 21702, USA
| | - Jeffrey R Kugelman
- United States Army Research Institute for Infectious Disease, Fort Detrick, Frederick, MD, 21702, USA
| | - Susana Guerra
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
- Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
- Departmento de Medicina Preventiva, Salud Publica y Microbiología, Universidad Autónoma de Madrid, 28029, Madrid, Spain
| | - Adolfo García-Sastre
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
- Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
- Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
- The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Isabel Cuesta
- Unidad de Bioinformática, Unidades Centrales Científico Técnicas, Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Maripaz P Sánchez-Seco
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28029, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Gustavo Palacios
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
- Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
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16
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Alpert JS. Medical Jeopardy Quiz: Zoonoses - What Disease Is Related to These Animals? Am J Med 2024; 137:293-294. [PMID: 37572745 DOI: 10.1016/j.amjmed.2023.07.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 07/26/2023] [Indexed: 08/14/2023]
Affiliation(s)
- Joseph S Alpert
- University of Arizona School of Medicine, TucsonEditor in Chief, The American Journal of Medicine.
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17
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Hämmerle M, Rymbekova A, Gelabert P, Sawyer S, Cheronet O, Bernardi P, Calvignac-Spencer S, Kuhlwilm M, Guellil M, Pinhasi R. Link between Monkeypox Virus Genomes from Museum Specimens and 1965 Zoo Outbreak. Emerg Infect Dis 2024; 30:816-818. [PMID: 38526306 PMCID: PMC10977839 DOI: 10.3201/eid3004.231546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2024] Open
Abstract
We used pathogen genomics to test orangutan specimens from a museum in Bonn, Germany, to identify the origin of the animals and the circumstances of their death. We found monkeypox virus genomes in the samples and determined that they represent cases from a 1965 outbreak at Rotterdam Zoo in Rotterdam, the Netherlands.
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Affiliation(s)
- Michelle Hämmerle
- University of Vienna, Vienna, Austria (M. Hämmerle, A. Rymbekova, P. Gelabert, S. Sawyer, O. Cheronet, P. Bernardi, M. Kuhlwilm, M. Guellil, R. Pinhasi)
- Helmholtz Centre for Infection Research, Greifswald, Germany (S. Calvignac-Spencer)
- University of Greifswald, Greifswald (S. Calvignac-Spencer)
| | - Aigerim Rymbekova
- University of Vienna, Vienna, Austria (M. Hämmerle, A. Rymbekova, P. Gelabert, S. Sawyer, O. Cheronet, P. Bernardi, M. Kuhlwilm, M. Guellil, R. Pinhasi)
- Helmholtz Centre for Infection Research, Greifswald, Germany (S. Calvignac-Spencer)
- University of Greifswald, Greifswald (S. Calvignac-Spencer)
| | - Pere Gelabert
- University of Vienna, Vienna, Austria (M. Hämmerle, A. Rymbekova, P. Gelabert, S. Sawyer, O. Cheronet, P. Bernardi, M. Kuhlwilm, M. Guellil, R. Pinhasi)
- Helmholtz Centre for Infection Research, Greifswald, Germany (S. Calvignac-Spencer)
- University of Greifswald, Greifswald (S. Calvignac-Spencer)
| | - Susanna Sawyer
- University of Vienna, Vienna, Austria (M. Hämmerle, A. Rymbekova, P. Gelabert, S. Sawyer, O. Cheronet, P. Bernardi, M. Kuhlwilm, M. Guellil, R. Pinhasi)
- Helmholtz Centre for Infection Research, Greifswald, Germany (S. Calvignac-Spencer)
- University of Greifswald, Greifswald (S. Calvignac-Spencer)
| | - Olivia Cheronet
- University of Vienna, Vienna, Austria (M. Hämmerle, A. Rymbekova, P. Gelabert, S. Sawyer, O. Cheronet, P. Bernardi, M. Kuhlwilm, M. Guellil, R. Pinhasi)
- Helmholtz Centre for Infection Research, Greifswald, Germany (S. Calvignac-Spencer)
- University of Greifswald, Greifswald (S. Calvignac-Spencer)
| | - Paolo Bernardi
- University of Vienna, Vienna, Austria (M. Hämmerle, A. Rymbekova, P. Gelabert, S. Sawyer, O. Cheronet, P. Bernardi, M. Kuhlwilm, M. Guellil, R. Pinhasi)
- Helmholtz Centre for Infection Research, Greifswald, Germany (S. Calvignac-Spencer)
- University of Greifswald, Greifswald (S. Calvignac-Spencer)
| | - Sébastien Calvignac-Spencer
- University of Vienna, Vienna, Austria (M. Hämmerle, A. Rymbekova, P. Gelabert, S. Sawyer, O. Cheronet, P. Bernardi, M. Kuhlwilm, M. Guellil, R. Pinhasi)
- Helmholtz Centre for Infection Research, Greifswald, Germany (S. Calvignac-Spencer)
- University of Greifswald, Greifswald (S. Calvignac-Spencer)
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18
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Brien SC, LeBreton M, Doty JB, Mauldin MR, Morgan CN, Pieracci EG, Ritter JM, Matheny A, Tafon BG, Tamoufe U, Missoup AD, Nwobegahay J, Takuo JM, Nkom F, Mouiche MMM, Feussom JMK, Wilkins K, Wade A, McCollum AM. Clinical Manifestations of an Outbreak of Monkeypox Virus in Captive Chimpanzees in Cameroon, 2016. J Infect Dis 2024; 229:S275-S284. [PMID: 38164967 PMCID: PMC11949251 DOI: 10.1093/infdis/jiad601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 12/16/2023] [Accepted: 12/19/2023] [Indexed: 01/03/2024] Open
Abstract
Monkeypox virus (MPXV) is a reemerging virus of global concern. An outbreak of clade I MPXV affected 20 captive chimpanzees in Cameroon in 2016. We describe the epidemiology, virology, phylogenetics, and clinical progression of this outbreak. Clinical signs included exanthema, facial swelling, perilaryngeal swelling, and eschar. Mpox can be lethal in captive chimpanzees, with death likely resulting from respiratory complications. We advise avoiding anesthesia in animals with respiratory signs to reduce the likelihood of death. This outbreak presented a risk to animal care staff. There is a need for increased awareness and a One Health approach to preparation for outbreaks in wildlife rescue centers in primate range states where MPXV occurs. Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures.
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Affiliation(s)
- Stephanie C. Brien
- Royal (Dick) School of Veterinary Studies and the Roslin Institute, Easter Bush Campus, The University of Edinburgh, Roslin, United Kingdom
- Ape Action Africa, Mefou Park, Cameroon
| | | | - Jeffrey B. Doty
- Division of High Consequence Pathogens and Pathology, US Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Matthew R. Mauldin
- Division of High Consequence Pathogens and Pathology, US Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Clint N. Morgan
- Division of High Consequence Pathogens and Pathology, US Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Emily G. Pieracci
- Division of High Consequence Pathogens and Pathology, US Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Jana M. Ritter
- Division of High Consequence Pathogens and Pathology, US Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Audrey Matheny
- Division of High Consequence Pathogens and Pathology, US Centers for Disease Control and Prevention, Atlanta, GA, USA
| | | | | | - Alain D. Missoup
- Zoology Unit, Laboratory of Biology and Physiology of Animal Organisms, Faculty of Science, University of Douala, Cameroon
| | | | | | | | - Moctar M. M. Mouiche
- Mosaic, Yaoundé, Cameroon
- School of Veterinary Medicine and Sciences, University of Ngaounderé, Cameroon
| | - Jean Marc K. Feussom
- Cameroon Epidemiological Network for Animal Diseases, Directorate of Veterinary Services, Ministry of Livestock, Fisheries and Animal Industries, Yaoundé, Cameroon
| | - Kimberly Wilkins
- Division of High Consequence Pathogens and Pathology, US Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Abel Wade
- National Veterinary Laboratory, Garoua, Cameroon
| | - Andrea M. McCollum
- Division of High Consequence Pathogens and Pathology, US Centers for Disease Control and Prevention, Atlanta, GA, USA
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19
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Abduljalil JM, Elfiky AA, AlKhazindar MM. Tepotinib and tivantinib as potential inhibitors for the serine/threonine kinase of the mpox virus: insights from structural bioinformatics analysis. J Biomol Struct Dyn 2024:1-11. [PMID: 38529847 DOI: 10.1080/07391102.2024.2323699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 02/21/2024] [Indexed: 03/27/2024]
Abstract
The serine/threonine kinase (STK) plays a central role as the primary kinase in poxviruses, directing phosphoryl transfer reactions. Such reactions are pivotal for the activation of certain proteins during viral replication, assembly, and maturation. Therefore, targeting this key protein is anticipated to impede virus replication. In this work, a structural bioinformatics approach was employed to evaluate the potential of drug-like kinase inhibitors in binding to the ATP-binding pocket on the STK of the Mpox virus. Virtual screening of known kinase inhibitors revealed that the top 10 inhibitors exhibited binding affinities ranging from -8.59 to -12.05 kcal/mol. The rescoring of compounds using the deep-learning default model in GNINA was performed to predict accurate binding poses. Subsequently, the top three inhibitors underwent unbiased molecular dynamics (MD) simulations for 100 ns. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis and Principal Component Analysis (PCA) suggested tepotinib as a competitive inhibitor for Mpox virus STK as evidenced by its binding free energy and the induction of similar conformational behavior of the enzyme. Nevertheless, it is sensible to experimentally test all top 10 compounds, as scoring functions and energy calculations may not consistently align with experimental findings. These insights are poised to provide an attempt to identify an effective inhibitor for the Mpox virus.
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Affiliation(s)
- Jameel M Abduljalil
- Department of Biological Sciences, Faculty of Applied Sciences, Thamar University, Dhamar, Yemen
| | - Abdo A Elfiky
- Department of Biophysics, Faculty of Science, Cairo University, Giza, Egypt
| | - Maha M AlKhazindar
- Department of Botany and Microbiology, Faculty of Science, Cairo University, Giza, Egypt
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20
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Quek ZBR, Ng SH. Hybrid-Capture Target Enrichment in Human Pathogens: Identification, Evolution, Biosurveillance, and Genomic Epidemiology. Pathogens 2024; 13:275. [PMID: 38668230 PMCID: PMC11054155 DOI: 10.3390/pathogens13040275] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/11/2024] [Accepted: 03/18/2024] [Indexed: 04/29/2024] Open
Abstract
High-throughput sequencing (HTS) has revolutionised the field of pathogen genomics, enabling the direct recovery of pathogen genomes from clinical and environmental samples. However, pathogen nucleic acids are often overwhelmed by those of the host, requiring deep metagenomic sequencing to recover sufficient sequences for downstream analyses (e.g., identification and genome characterisation). To circumvent this, hybrid-capture target enrichment (HC) is able to enrich pathogen nucleic acids across multiple scales of divergences and taxa, depending on the panel used. In this review, we outline the applications of HC in human pathogens-bacteria, fungi, parasites and viruses-including identification, genomic epidemiology, antimicrobial resistance genotyping, and evolution. Importantly, we explored the applicability of HC to clinical metagenomics, which ultimately requires more work before it is a reliable and accurate tool for clinical diagnosis. Relatedly, the utility of HC was exemplified by COVID-19, which was used as a case study to illustrate the maturity of HC for recovering pathogen sequences. As we unravel the origins of COVID-19, zoonoses remain more relevant than ever. Therefore, the role of HC in biosurveillance studies is also highlighted in this review, which is critical in preparing us for the next pandemic. We also found that while HC is a popular tool to study viruses, it remains underutilised in parasites and fungi and, to a lesser extent, bacteria. Finally, weevaluated the future of HC with respect to bait design in the eukaryotic groups and the prospect of combining HC with long-read HTS.
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Affiliation(s)
- Z. B. Randolph Quek
- Defence Medical & Environmental Research Institute, DSO National Laboratories, Singapore 117510, Singapore
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21
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Kumar A, Singh N, Anvikar AR, Misra G. Monkeypox virus: insights into pathogenesis and laboratory testing methods. 3 Biotech 2024; 14:67. [PMID: 38357674 PMCID: PMC10861412 DOI: 10.1007/s13205-024-03920-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Accepted: 01/07/2024] [Indexed: 02/16/2024] Open
Abstract
The monkeypox virus (MPXV) is a zoonotic pathogen that transmits between monkeys and humans, exhibiting clinical similarities with the smallpox virus. Studies on the immunopathogenesis of MPXV revealed that an initial strong innate immune response is elicited on viral infection that subsequently helps in circumventing the host defense. Once the World Health Organization (WHO) declared it a global public health emergency in July 2022, it became essential to clearly demarcate the MPXV-induced symptoms from other viral infections. We have exhaustively searched the various databases involving Google Scholar, PubMed, and Medline to extract the information comprehensively compiled in this review. The primary focus of this review is to describe the diagnostic methods for MPXV such as polymerase chain reaction (PCR), and serological assays, along with developments in viral isolation, imaging techniques, and next-generation sequencing. These innovative technologies have the potential to greatly enhance the accuracy of diagnostic procedures. Significant discoveries involving MPXV immunopathogenesis have also been highlighted. Overall, this will be a knowledge repertoire that will be crucial for the development of efficient monitoring and control strategies in response to the MPXV infection helping clinicians and researchers in formulating healthcare strategies.
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Affiliation(s)
- Anoop Kumar
- National Institute of Biologicals, A-32, Sector-62, Institutional Area, Noida, U.P. 201309 India
| | - Neeraj Singh
- National Institute of Biologicals, A-32, Sector-62, Institutional Area, Noida, U.P. 201309 India
| | - Anupkumar R. Anvikar
- National Institute of Biologicals, A-32, Sector-62, Institutional Area, Noida, U.P. 201309 India
| | - Gauri Misra
- National Institute of Biologicals, A-32, Sector-62, Institutional Area, Noida, U.P. 201309 India
- Head Molecular Diagnostics and COVID-19 Kit Testing Laboratory, National Institute of Biologicals (Ministry of Health and Family Welfare), Noida, U.P. 201309 India
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22
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Friederici AD, Wittig RM, Anwander A, Eichner C, Gräßle T, Jäger C, Kirilina E, Lipp I, Düx A, Edwards LJ, Girard-Buttoz C, Jauch A, Kopp KS, Paquette M, Pine KJ, Unwin S, Haun DBM, Leendertz FH, McElreath R, Morawski M, Gunz P, Weiskopf N, Crockford C. Brain structure and function: a multidisciplinary pipeline to study hominoid brain evolution. Front Integr Neurosci 2024; 17:1299087. [PMID: 38260006 PMCID: PMC10800984 DOI: 10.3389/fnint.2023.1299087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 12/07/2023] [Indexed: 01/24/2024] Open
Abstract
To decipher the evolution of the hominoid brain and its functions, it is essential to conduct comparative studies in primates, including our closest living relatives. However, strong ethical concerns preclude in vivo neuroimaging of great apes. We propose a responsible and multidisciplinary alternative approach that links behavior to brain anatomy in non-human primates from diverse ecological backgrounds. The brains of primates observed in the wild or in captivity are extracted and fixed shortly after natural death, and then studied using advanced MRI neuroimaging and histology to reveal macro- and microstructures. By linking detailed neuroanatomy with observed behavior within and across primate species, our approach provides new perspectives on brain evolution. Combined with endocranial brain imprints extracted from computed tomographic scans of the skulls these data provide a framework for decoding evolutionary changes in hominin fossils. This approach is poised to become a key resource for investigating the evolution and functional differentiation of hominoid brains.
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Affiliation(s)
- Angela D. Friederici
- Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Roman M. Wittig
- Evolution of Brain Connectivity Project, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
- Institute for Cognitive Sciences Marc Jeannerod, UMR CNRS, University Claude Bernard Lyon, Bron, France
- Taï Chimpanzee Project, CSRS, Abidjan, Côte d'Ivoire
| | - Alfred Anwander
- Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Cornelius Eichner
- Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Tobias Gräßle
- Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, Berlin, Germany
| | - Carsten Jäger
- Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
- Medical Faculty, Center of Neuropathology and Brain Research, Paul Flechsig Institute, University of Leipzig, Leipzig, Germany
| | - Evgeniya Kirilina
- Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Ilona Lipp
- Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Ariane Düx
- Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, Berlin, Germany
- Helmholtz Institute for One Health, University of Greifswald, Greifswald, Germany
| | - Luke J. Edwards
- Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Cédric Girard-Buttoz
- Evolution of Brain Connectivity Project, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
- Institute for Cognitive Sciences Marc Jeannerod, UMR CNRS, University Claude Bernard Lyon, Bron, France
| | - Anna Jauch
- Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Kathrin S. Kopp
- Department of Comparative Cultural Psychology, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
| | - Michael Paquette
- Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Kerrin J. Pine
- Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Steve Unwin
- School of Bioscience, University of Birmingham, Birmingham, United Kingdom
| | - Daniel B. M. Haun
- Department of Comparative Cultural Psychology, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
| | - Fabian H. Leendertz
- Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, Berlin, Germany
- Helmholtz Institute for One Health, University of Greifswald, Greifswald, Germany
| | - Richard McElreath
- Department of Human Behavior, Ecology and Culture, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
| | - Markus Morawski
- Medical Faculty, Center of Neuropathology and Brain Research, Paul Flechsig Institute, University of Leipzig, Leipzig, Germany
| | - Philipp Gunz
- Department of Human Origins, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
| | - Nikolaus Weiskopf
- Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
- Faculty of Physics and Earth System Sciences, Felix Bloch Institute for Solid State Physics, Leipzig University, Leipzig, Germany
| | - Catherine Crockford
- Evolution of Brain Connectivity Project, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
- Institute for Cognitive Sciences Marc Jeannerod, UMR CNRS, University Claude Bernard Lyon, Bron, France
- Taï Chimpanzee Project, CSRS, Abidjan, Côte d'Ivoire
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23
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Ogunleye SC, Akinsulie OC, Aborode AT, Olorunshola MM, Gbore D, Oladoye M, Adesola RO, Gbadegoye JO, Olatoye BJ, Lawal MA, Bakare AB, Adekanye O, Chinyere EC. The re-emergence and transmission of Monkeypox virus in Nigeria: the role of one health. Front Public Health 2024; 11:1334238. [PMID: 38249416 PMCID: PMC10797020 DOI: 10.3389/fpubh.2023.1334238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 12/08/2023] [Indexed: 01/23/2024] Open
Abstract
The Monkeypox virus, commonly abbreviated as mpox, is a viral zoonosis that is experiencing a resurgence in prevalence. It is endemic to regions of West and Central Africa that are characterized by dense forested areas. Various measures pertaining to animals, humans, and the environment have been recognized as potential factors and catalysts for the spread of the disease throughout the impacted regions of Africa. This study examines the various factors contributing to the transmission of the virus in Nigeria, with a particular focus on the animal-human and inter-human modes of transmission in rural communities and healthcare facilities. The One Health approach was emphasized as crucial in the prevention and management of this issue. Literature suggests that preventing repeated zoonotic introductions could potentially halt the transmission of the mpox virus from animal to human hosts, leading to a potential decrease in human infections.
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Affiliation(s)
- Seto C. Ogunleye
- Faculty of Veterinary Medicine, University of Ibadan, Ibada, Nigeria
| | - Olalekan C. Akinsulie
- Department of Veterinary Biochemistry, Nigeria College of Veterinary Medicine, University of Ibadan, Ibada, Nigeria
| | | | - Mercy M. Olorunshola
- Department of Pharmaceutical Microbiology, Pharmacy, University of Ibadan, Ibada, Nigeria
| | - Damilola Gbore
- Faculty of Veterinary Medicine, University of Ibadan, Ibada, Nigeria
| | | | - Ridwan O. Adesola
- Faculty of Veterinary Medicine, University of Ibadan, Ibada, Nigeria
| | - Joy O. Gbadegoye
- Department of Veterinary Biochemistry, Nigeria College of Veterinary Medicine, University of Ibadan, Ibada, Nigeria
- Healthy Africans Platform, Research and Development, Ibada, Nigeria
| | | | - Mariam A. Lawal
- Department of Biochemistry, Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria
| | - Akeem B. Bakare
- Faculty of Veterinary Medicine, University of Ibadan, Ibada, Nigeria
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24
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Atasoy MO, Naggar RFE, Rohaim MA, Munir M. Zoonotic and Zooanthroponotic Potential of Monkeypox. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1451:75-90. [PMID: 38801572 DOI: 10.1007/978-3-031-57165-7_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2024]
Abstract
The current multicounty outbreak of monkeypox virus (MPXV) posed an emerging and continued challenge to already strained public healthcare sector, around the globe. Since its first identification, monkeypox disease (mpox) remained enzootic in Central and West African countries where reports of human cases are sporadically described. Recent trends in mpox spread outside the Africa have highlighted increased incidence of spillover of the MPXV from animal to humans. While nature of established animal reservoirs remained undefined, several small mammals including rodents, carnivores, lagomorphs, insectivores, non-human primates, domestic/farm animals, and several species of wildlife are proposed to be carrier of the MPXV infection. There are established records of animal-to-human (zoonotic) spread of MPXV through close interaction of humans with animals by eating bushmeat, contracting bodily fluids or trading possibly infected animals. In contrast, there are reports and increasing possibilities of human-to-animal (zooanthroponotic) spread of the MPXV through petting and close interaction with pet owners and animal care workers. We describe here the rationales and molecular factors which predispose the spread of MPXV not only amongst humans but also from animals to humans. A range of continuing opportunities for the spread and evolution of MPXV are discussed to consider risks beyond the currently identified groups. With the possibility of MPXV establishing itself in animal reservoirs, continued and broad surveillance, investigation into unconventional transmissions, and exploration of spillover events are warranted.
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Affiliation(s)
- Mustafa O Atasoy
- Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Furness College, Lancaster University, Tower Ave, Bailrigg, LA1 4YG, UK
| | - Rania F El Naggar
- Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Furness College, Lancaster University, Tower Ave, Bailrigg, LA1 4YG, UK
| | - Mohammed A Rohaim
- Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Furness College, Lancaster University, Tower Ave, Bailrigg, LA1 4YG, UK
| | - Muhammad Munir
- Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Furness College, Lancaster University, Tower Ave, Bailrigg, LA1 4YG, UK.
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25
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Kalaba MH, El-Sherbiny GM, Sharaf MH, Farghal EE. Biological Characteristics and Pathogenesis of Monkeypox Virus: An Overview. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1451:91-109. [PMID: 38801573 DOI: 10.1007/978-3-031-57165-7_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2024]
Abstract
Although the smallpox virus has been eradicated worldwide, the World Health Organization (WHO) has issued a warning about the virus's potential to propagate globally. The WHO labeled monkeypox a world public health emergency in July 2022, requiring urgent prevention and treatment. The monkeypox virus is a part of the Poxviridae family, Orthopoxvirus genus, and is accountable for smallpox, which has killed over a million people in the past. Natural hosts of the virus include squirrels, Gambian rodents, chimpanzees, and other monkeys. The monkeypox virus has transmitted to humans through primary vectors (various animal species) and secondary vectors, including direct touch with lesions, breathing particles from body fluids, and infected bedding. The viral particles are ovoid or brick-shaped, 200-250 nm in diameter, contain a single double-stranded DNA molecule, and reproduce only in the cytoplasm of infected cells. Monkeypox causes fever, cold, muscle pains, headache, fatigue, and backache. The phylogenetic investigation distinguished between two genetic clades of monkeypox: the more pathogenic Congo Basin clade and the West Africa clade. In recent years, the geographical spread of the human monkeypox virus has accelerated despite a paucity of information regarding the disease's emergence, ecology, and epidemiology. Using lesion samples and polymerase chain reaction (PCR), the monkeypox virus was diagnosed. In the USA, the improved Ankara vaccine can now be used to protect people who are at a higher risk of getting monkeypox. Antivirals that we have now work well against smallpox and may stop the spread of monkeypox, but there is no particular therapy for monkeypox.
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Affiliation(s)
- Mohamed H Kalaba
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt
| | - Gamal M El-Sherbiny
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt.
| | - Mohammed H Sharaf
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt
| | - Eman E Farghal
- Clinical and Chemical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt
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26
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Taha AM, Katamesh BE, Hassan AR, Abdelwahab OA, Rustagi S, Nguyen D, Silva-Cajaleon K, Rodriguez-Morales AJ, Mohanty A, Bonilla-Aldana DK, Sah R. Environmental detection and spreading of mpox in healthcare settings: a narrative review. Front Microbiol 2023; 14:1272498. [PMID: 38179458 PMCID: PMC10764434 DOI: 10.3389/fmicb.2023.1272498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 11/16/2023] [Indexed: 01/06/2024] Open
Abstract
Monkeypox virus (MPXV), which causes Monkeypox (Mpox), has recently been found outside its usual geographic distribution and has spread to 117 different nations. The World Health Organization (WHO) designated the epidemic a Public Health Emergency of International Concern (PHEIC). Humans are at risk from MPXV's spread, which has raised concerns, particularly in the wake of the SARS-CoV-2 epidemic. The risk of virus transmission may rise due to the persistence of MPXV on surfaces or in wastewater. The risk of infection may also increase due to insufficient wastewater treatment allowing the virus to survive in the environment. To manage the infection cycle, it is essential to investigate the viral shedding from various lesions, the persistence of MPXV on multiple surfaces, and the length of surface contamination. Environmental contamination may contribute to virus persistence and future infection transmission. The best possible infection control and disinfection techniques depend on this knowledge. It is thought to spread mainly through intimate contact. However, the idea of virus transmission by environmental contamination creates great concern and discussion. There are more cases of environmental surfaces and wastewater contamination. We will talk about wastewater contamination, methods of disinfection, and the present wastewater treatment in this review as well as the persistence of MPXV on various environmental surfaces.
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Affiliation(s)
- Amira Mohamed Taha
- Faculty of Medicine, Fayoum University, Fayoum, Egypt
- Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, United States
| | - Basant E. Katamesh
- Faculty of Medicine, Tanta University, Tanta, Egypt
- Mayo Clinic, Rochester, MN, United States
| | | | - Omar Ahmed Abdelwahab
- Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, United States
- Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Sarvesh Rustagi
- School of Applied and Life Sciences, Uttaranchal University, Dehradun, India
| | - Dang Nguyen
- Massachusetts General Hospital, Corrigan Minehan Heart Center and Harvard Medical School, Boston, MA, United States
| | | | - Alfonso J. Rodriguez-Morales
- Faculty of Environmental Sciences, Universidad Científica del Sur, Lima, Peru
- Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de lasAméricas-Institución Universitaria Visión de las Américas, Pereira, Colombia
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon
| | - Aroop Mohanty
- Department of Clinical Microbiology, All India Institute of Medical Sciences, Gorakhpur, India
| | | | - Ranjit Sah
- Tribhuvan University Teaching Hospital, Kathmandu, Nepal
- Department of Clinical Microbiology, DY Patil Medical College, Hospital and Research Centre, DY Patil Vidyapeeth, Pune, India
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Zhao P, Shao N, Dong J, Su H, Sui H, Zhang T, Yang F. Genetic diversity and characterization of rhinoviruses from Chinese clinical samples with a global perspective. Microbiol Spectr 2023; 11:e0084023. [PMID: 37733296 PMCID: PMC10715137 DOI: 10.1128/spectrum.00840-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 08/03/2023] [Indexed: 09/22/2023] Open
Abstract
IMPORTANCE Based on clinical samples collected in China, we detected and reported 22 types for the first time in China, as well as three types for the first time in Asia, and reported their genetic characteristics and diversity. We identified a novel type of Rhinovirus (RV), A110, highlighting its unique genetic features. We annotated the genomic structure and serotype of all the existing RV sequences in the database, and four novel RV types were identified and their genetic diversity reported. Combined with the sequence annotation, we constructed a complete VP1 data set of RV and conducted the first large-scale evolutionary dynamics analysis of RV. Based on a high-quality data set, we conducted a comprehensive analysis of the guanine-cytosine (GC) content variations among serotypes of RVs. This study provides crucial theoretical support and valuable data for understanding RV's genetic diversity and developing antiviral strategies.
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Affiliation(s)
- Peng Zhao
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nan Shao
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie Dong
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haoxiang Su
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongtao Sui
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ting Zhang
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Yang
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China
- State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, China
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Houldcroft CJ, Underdown S. Infectious disease in the Pleistocene: Old friends or old foes? AMERICAN JOURNAL OF BIOLOGICAL ANTHROPOLOGY 2023; 182:513-531. [PMID: 38006200 DOI: 10.1002/ajpa.24737] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 03/01/2023] [Accepted: 03/14/2023] [Indexed: 11/26/2023]
Abstract
The impact of endemic and epidemic disease on humans has traditionally been seen as a comparatively recent historical phenomenon associated with the Neolithisation of human groups, an increase in population size led by sedentarism, and increasing contact with domesticated animals as well as species occupying opportunistic symbiotic and ectosymbiotic relationships with humans. The orthodox approach is that Neolithisation created the conditions for increasing population size able to support a reservoir of infectious disease sufficient to act as selective pressure. This orthodoxy is the result of an overly simplistic reliance on skeletal data assuming that no skeletal lesions equated to a healthy individual, underpinned by the assumption that hunter-gatherer groups were inherently healthy while agricultural groups acted as infectious disease reservoirs. The work of van Blerkom, Am. J. Phys. Anthropol., vol. suppl 37 (2003), Wolfe et al., Nature, vol. 447 (2007) and Houldcroft and Underdown, Am. J. Phys. Anthropol., vol. 160, (2016) has changed this landscape by arguing that humans and pathogens have long been fellow travelers. The package of infectious diseases experienced by our ancient ancestors may not be as dissimilar to modern infectious diseases as was once believed. The importance of DNA, from ancient and modern sources, to the study of the antiquity of infectious disease, and its role as a selective pressure cannot be overstated. Here we consider evidence of ancient epidemic and endemic infectious diseases with inferences from modern and ancient human and hominin DNA, and from circulating and extinct pathogen genomes. We argue that the pandemics of the past are a vital tool to unlock the weapons needed to fight pandemics of the future.
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Affiliation(s)
| | - Simon Underdown
- Human Origins and Palaeoenvironmental Research Group, School of Social Sciences, Oxford Brookes University, Oxford, UK
- Center for Microbial Ecology and Genomics, Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria, South Africa
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29
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O’Toole Á, Neher RA, Ndodo N, Borges V, Gannon B, Gomes JP, Groves N, King DJ, Maloney D, Lemey P, Lewandowski K, Loman N, Myers R, Omah IF, Suchard MA, Worobey M, Chand M, Ihekweazu C, Ulaeto D, Adetifa I, Rambaut A. APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016. Science 2023; 382:595-600. [PMID: 37917680 PMCID: PMC10880385 DOI: 10.1126/science.adg8116] [Citation(s) in RCA: 55] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 09/21/2023] [Indexed: 11/04/2023]
Abstract
Historically, mpox has been characterized as an endemic zoonotic disease that transmits through contact with the reservoir rodent host in West and Central Africa. However, in May 2022, human cases of mpox were detected spreading internationally beyond countries with known endemic reservoirs. When the first cases from 2022 were sequenced, they shared 42 nucleotide differences from the closest mpox virus (MPXV) previously sampled. Nearly all these mutations are characteristic of the action of APOBEC3 deaminases, host enzymes with antiviral function. Assuming APOBEC3 editing is characteristic of human MPXV infection, we developed a dual-process phylogenetic molecular clock that-inferring a rate of ~6 APOBEC3 mutations per year-estimates that MPXV has been circulating in humans since 2016. These observations of sustained MPXV transmission present a fundamental shift to the perceived paradigm of MPXV epidemiology as a zoonosis and highlight the need for revising public health messaging around MPXV as well as outbreak management and control.
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Affiliation(s)
- Áine O’Toole
- Institute of Ecology & Evolution, University of Edinburgh; Edinburgh, EH9 3FL, United Kingdom
| | - Richard A. Neher
- Biozentrum, University of Basel and Swiss Institute of Bioinformatics; Basel, Switzerland
| | - Nnaemeka Ndodo
- Nigeria Centers for Disease Control and Prevention; Abuja, Nigeria
| | - Vitor Borges
- National Institute of Health Doutor Ricardo Jorge (INSA); Lisbon, Portugal
| | - Ben Gannon
- UK Health Security Agency, Porton Down; Salisbury, United Kingdom
| | - João Paulo Gomes
- National Institute of Health Doutor Ricardo Jorge (INSA); Lisbon, Portugal
- Veterinary and Animal Research Centre (CECAV), Faculty of Veterinary Medicine, Lusófona University, Lisbon, Portugal
| | - Natalie Groves
- UK Health Security Agency; London, E14 5EA, United Kingdom
| | - David J King
- CBR Division, Defence Science and Technology Laboratory; Salisbury SP4 0JQ, United Kingdom
| | - Daniel Maloney
- Institute of Ecology & Evolution, University of Edinburgh; Edinburgh, EH9 3FL, United Kingdom
| | - Philippe Lemey
- Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven; Leuven, Belgium
| | | | - Nicholas Loman
- UK Health Security Agency; London, E14 5EA, United Kingdom
- University of Birmingham; Birmingham, United Kingdom
| | - Richard Myers
- UK Health Security Agency; London, E14 5EA, United Kingdom
| | - Ifeanyi F. Omah
- Institute of Ecology & Evolution, University of Edinburgh; Edinburgh, EH9 3FL, United Kingdom
- Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria
| | - Marc A. Suchard
- Department of Biostatistics, Fielding School of Public Health, University of California; Los Angeles, California, USA
| | - Michael Worobey
- Department of Ecology and Evolutionary Biology, University of Arizona; Tucson, Arizona, USA
| | - Meera Chand
- UK Health Security Agency; London, E14 5EA, United Kingdom
| | - Chikwe Ihekweazu
- Nigeria Centers for Disease Control and Prevention; Abuja, Nigeria
| | - David Ulaeto
- UK Health Security Agency; London, E14 5EA, United Kingdom
| | - Ifedayo Adetifa
- Nigeria Centers for Disease Control and Prevention; Abuja, Nigeria
| | - Andrew Rambaut
- Institute of Ecology & Evolution, University of Edinburgh; Edinburgh, EH9 3FL, United Kingdom
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30
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Mitjà O, Padovese V, Folch C, Rossoni I, Marks M, Rodríguez i Arias MA, Telenti A, Ciuffi A, Blondeel K, Mårdh O, Casabona J. Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe. THE LANCET REGIONAL HEALTH. EUROPE 2023; 34:100742. [PMID: 37927427 PMCID: PMC10625005 DOI: 10.1016/j.lanepe.2023.100742] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 09/11/2023] [Accepted: 09/15/2023] [Indexed: 11/07/2023]
Abstract
In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.
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Affiliation(s)
- Oriol Mitjà
- Skin Neglected Tropical Diseases and Sexually Transmitted Infections Section, Hospital Universitari Germans Trías i Pujol, Badalona, Spain
- Fight Infectious Diseases Foundation, Badalona, Spain
- School of Medicine and Health Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea
| | - Valeska Padovese
- Genitourinary Clinic, Department of Dermatology and Venereology, Mater Dei Hospital, Msida, Malta
| | - Cinta Folch
- Centre of Epidemiological Studies of HIV/AIDS and STI of Catalonia (CEEISCAT), Health Department, Generalitat de Catalunya, Badalona, Spain
- Germans Trias I Pujol Research Institute (IGTP), Campus Can Ruti, Badalona, Spain
- CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain
| | - Isotta Rossoni
- Van Vollenhoven Institute for Law, Governance and Society, Leiden University, Netherland
| | - Michael Marks
- Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, United Kingdom
- Division of Infection and Immunology, University College London, London, UK
- Hospital for Tropical Diseases, University College London Hospital, London, UK
| | - Miquel Angel Rodríguez i Arias
- Skin Neglected Tropical Diseases and Sexually Transmitted Infections Section, Hospital Universitari Germans Trías i Pujol, Badalona, Spain
- Fight Infectious Diseases Foundation, Badalona, Spain
| | | | - Angela Ciuffi
- Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Karel Blondeel
- Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Otilia Mårdh
- STI, Blood Borne Viruses and TB Section, Disease Programmes Unit, European Centre for Disease Prevention and Control (ECDC), Solna, Sweden
| | - Jordi Casabona
- Centre of Epidemiological Studies of HIV/AIDS and STI of Catalonia (CEEISCAT), Health Department, Generalitat de Catalunya, Badalona, Spain
- Germans Trias I Pujol Research Institute (IGTP), Campus Can Ruti, Badalona, Spain
- CIBER Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain
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31
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Molina IS, Jimenez-Vasquez V, Lizarraga W, Sevilla N, Hurtado V, Padilla-Rojas C. Sub-lineage B.1.6 of hMPXV in a global context: Phylogeny and epidemiology. J Med Virol 2023; 95:e29056. [PMID: 37671858 DOI: 10.1002/jmv.29056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 07/26/2023] [Accepted: 08/14/2023] [Indexed: 09/07/2023]
Abstract
During the 2022 COVID-19 pandemic, monkeypox emerged as a significant threat to global health. The virus responsible for the disease, the human monkeypox virus (hMPXV), underwent various genetic changes, resulting in the emergence of over a dozen distinct lineages, which could be identified by only a small number of unique mutations. As of January 25, 2023, genomic information of hMPXV generated had reached 4632 accessions in the GISAID database. In this study, we aimed to investigate the epidemiological and phylogenetic characteristics of the B.1.6 sub-lineage of hMPXV in Peru, compared with other circulating sub-lineages during the global outbreak. The B.1.6 sub-lineage, characterized by the 111029G>A mutation, was estimated to have emerged in June 2022 and was found mainly in Peru. Most cases (95.8%) were men with an average age of 33 years, and nearly half of the patients had HIV, of whom only 77.35% received antiretroviral therapy. Our findings revealed that the B.1.6, B.1.4, and B.1.2 sub-lineages were well represented and had a higher number of mutations despite having the lowest media substitution rates per site per year. Moreover, it was estimated that B.1.2 and B.1.4 appeared in February 2022 and were the first two sub-lineages to emerge. A mutation profile was also obtained for each sub-lineage, reflecting that several mutations had a pattern similar to the characteristic mutation. This study provides the first estimation of the substitution rate and ancestry of each monkeypox sub-lineage belonging to the 2022 outbreak. Based on our findings, continued genomic surveillance of monkeypox is necessary to understand better and track the evolution of the virus.
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Affiliation(s)
- Iris S Molina
- Area de Innovacion y Desarrollo Tecnológico, Centro Nacional de Salud Pública, Instituto Nacional de Salud, Lima, Peru
| | - Victor Jimenez-Vasquez
- Area de Innovacion y Desarrollo Tecnológico, Centro Nacional de Salud Pública, Instituto Nacional de Salud, Lima, Peru
| | - Wendy Lizarraga
- Area de Innovacion y Desarrollo Tecnológico, Centro Nacional de Salud Pública, Instituto Nacional de Salud, Lima, Peru
| | - Nieves Sevilla
- Area de Innovacion y Desarrollo Tecnológico, Centro Nacional de Salud Pública, Instituto Nacional de Salud, Lima, Peru
| | - Veronica Hurtado
- Area de Innovacion y Desarrollo Tecnológico, Centro Nacional de Salud Pública, Instituto Nacional de Salud, Lima, Peru
| | - Carlos Padilla-Rojas
- Area de Innovacion y Desarrollo Tecnológico, Centro Nacional de Salud Pública, Instituto Nacional de Salud, Lima, Peru
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32
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Dunay E, Rukundo J, Atencia R, Cole MF, Cantwell A, Emery Thompson M, Rosati AG, Goldberg TL. Viruses in saliva from sanctuary chimpanzees (Pan troglodytes) in Republic of Congo and Uganda. PLoS One 2023; 18:e0288007. [PMID: 37384730 PMCID: PMC10310015 DOI: 10.1371/journal.pone.0288007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 06/16/2023] [Indexed: 07/01/2023] Open
Abstract
Pathogen surveillance for great ape health monitoring has typically been performed on non-invasive samples, primarily feces, in wild apes and blood in sanctuary-housed apes. However, many important primate pathogens, including known zoonoses, are shed in saliva and transmitted via oral fluids. Using metagenomic methods, we identified viruses in saliva samples from 46 wild-born, sanctuary-housed chimpanzees at two African sanctuaries in Republic of Congo and Uganda. In total, we identified 20 viruses. All but one, an unclassified CRESS DNA virus, are classified in five families: Circoviridae, Herpesviridae, Papillomaviridae, Picobirnaviridae, and Retroviridae. Overall, viral prevalence ranged from 4.2% to 87.5%. Many of these viruses are ubiquitous in primates and known to replicate in the oral cavity (simian foamy viruses, Retroviridae; a cytomegalovirus and lymphocryptovirus; Herpesviridae; and alpha and gamma papillomaviruses, Papillomaviridae). None of the viruses identified have been shown to cause disease in chimpanzees or, to our knowledge, in humans. These data suggest that the risk of zoonotic viral disease from chimpanzee oral fluids in sanctuaries may be lower than commonly assumed.
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Affiliation(s)
- Emily Dunay
- Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Joshua Rukundo
- Ngamba Island Chimpanzee Sanctuary / Chimpanzee Trust, Entebbe, Uganda
| | - Rebeca Atencia
- Jane Goodall Institute Congo, Pointe-Noire, Republic of Congo
| | - Megan F. Cole
- Department of Anthropology, University of New Mexico, Albuquerque, New Mexico, United States of America
| | - Averill Cantwell
- Department of Psychology, University of Michigan, Ann Arbor, Michigan, United States of America
| | - Melissa Emery Thompson
- Department of Anthropology, University of New Mexico, Albuquerque, New Mexico, United States of America
| | - Alexandra G. Rosati
- Department of Psychology, University of Michigan, Ann Arbor, Michigan, United States of America
- Department of Anthropology, University of Michigan, Ann Arbor, Michigan, United States of America
| | - Tony L. Goldberg
- Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
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33
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Besombes C, Mbrenga F, Malaka C, Gonofio E, Schaeffer L, Konamna X, Selekon B, Namsenei-Dankpea J, Gildas Lemon C, Landier J, von Platen C, Gessain A, Manuguerra JC, Fontanet A, Nakouné E. Investigation of a mpox outbreak in Central African Republic, 2021-2022. One Health 2023; 16:100523. [PMID: 36950196 PMCID: PMC9988319 DOI: 10.1016/j.onehlt.2023.100523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 03/01/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
Human monkeypox virus is spreading globally, and more information is required about its epidemiological and clinical disease characteristics in endemic countries. We report the investigation of an outbreak in November 2021 in Central African Republic (CAR). The primary case, a hunter, fell ill after contact with a non-human primate at the frontier between forest and savannah. The ensuing investigation in a small nearby town concerned two families and four waves of inter-human transmission, with 14 confirmed cases, 11 suspected cases and 17 non-infected contacts, and a secondary attack rate of 59.5% (25/42). Complications were observed in 12 of the 19 (63.2%) confirmed and suspected cases with available clinical follow-up data: eight cases of bronchopneumonia, two of severe dehydration, one corneal ulcer, one abscess, two cutaneous superinfections, and six cutaneous sequelae (cheloid scars, or depigmentation). There was one death, giving a case fatality ratio of 1/25 (4.0%) for confirmed and suspected cases. This outbreak, with the largest number of confirmed cases ever described in CAR, confirms the potential severity of the disease associated with clade I monkeypox viruses, and highlights the need for rapid control over virus circulation to prevent the further national and international spread of infection.
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Affiliation(s)
- C Besombes
- Institut Pasteur, Université Paris Cité, Epidemiology of Emerging Diseases, 75015 Paris, France
- Sorbonne Université, Paris, France
| | - F Mbrenga
- Institut Pasteur, Bangui, République Centrafricaine - Department of Arboviruses, Emerging Viruses and zoonosis, Central African Republic
| | - C Malaka
- Institut Pasteur, Bangui, République Centrafricaine - Department of Arboviruses, Emerging Viruses and zoonosis, Central African Republic
| | - E Gonofio
- Institut Pasteur, Bangui, République Centrafricaine - Department of Arboviruses, Emerging Viruses and zoonosis, Central African Republic
| | - L Schaeffer
- Institut Pasteur, Université Paris Cité, Epidemiology of Emerging Diseases, 75015 Paris, France
| | - X Konamna
- Institut Pasteur, Bangui, République Centrafricaine - Department of Arboviruses, Emerging Viruses and zoonosis, Central African Republic
| | - B Selekon
- Institut Pasteur, Bangui, République Centrafricaine - Department of Arboviruses, Emerging Viruses and zoonosis, Central African Republic
| | - J Namsenei-Dankpea
- Institut Pasteur, Bangui, République Centrafricaine - Department of Arboviruses, Emerging Viruses and zoonosis, Central African Republic
| | - C Gildas Lemon
- Institut Pasteur, Bangui, République Centrafricaine - Department of Arboviruses, Emerging Viruses and zoonosis, Central African Republic
| | - J Landier
- IRD, Aix Marseille Université, INSERM - SESSTIM, Aix Marseille Institute of Public Health, ISSPAM, Marseille, France
| | - C von Platen
- Institut Pasteur Paris- Centre de Recherche Translationnelle- CC, France
| | - A Gessain
- Institut Pasteur, Université Paris Cité, Epidemiology of Emerging Diseases, 75015 Paris, France
- Université Paris Cité, CNRS UMR 3569 - Unité Épidémiologie et Physiopathologie des Virus Oncogènes, France
| | - J C Manuguerra
- Environment and Infectious Risk Research Unit, Laboratory for Urgent Response to Biological Threats (ERI-CIBU), France
| | - A Fontanet
- Institut Pasteur, Université Paris Cité, Epidemiology of Emerging Diseases, 75015 Paris, France
- Conservatoire National des Arts et Métiers, PACRI Unit, Paris, France
| | - E Nakouné
- Institut Pasteur, Bangui, République Centrafricaine - Department of Arboviruses, Emerging Viruses and zoonosis, Central African Republic
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34
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Brinkmann A, Kohl C, Pape K, Bourquain D, Thürmer A, Michel J, Schaade L, Nitsche A. Extensive ITR expansion of the 2022 Mpox virus genome through gene duplication and gene loss. Virus Genes 2023:10.1007/s11262-023-02002-1. [PMID: 37256469 DOI: 10.1007/s11262-023-02002-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 04/29/2023] [Indexed: 06/01/2023]
Abstract
Poxviruses are known to evolve slower than RNA viruses with only 1-2 mutations/genome/year. Rather than single mutations, rearrangements such as gene gain and loss, which have been discussed as a possible driver for host adaption, were described in poxviruses. In 2022 and 2023 the world is being challenged by the largest global outbreak so far of Mpox virus, and the virus seems to have established itself in the human community for an extended period of time. Here, we report five Mpox virus genomes from Germany with extensive gene duplication and loss, leading to the expansion of the ITR regions from 6400 to up to 24,600 bp. We describe duplications of up to 18,200 bp to the opposed genome end, and deletions at the site of insertion of up to 16,900 bp. Deletions and duplications of genes with functions of supposed immune modulation, virulence and host adaption as B19R, B21R, B22R and D10L are described. In summary, we highlight the need for monitoring rearrangements of the Mpox virus genome rather than for monitoring single mutations only.
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Affiliation(s)
- Annika Brinkmann
- Centre for Biological Threats and Special Pathogens, WHO Collaborating Centre for Emerging Infections and Biological Threats, Highly Pathogenic Viruses, German Consultant Laboratory for Poxviruses, Robert Koch Institute, Seestraße 10, 13353, Berlin, Germany.
| | - Claudia Kohl
- Centre for Biological Threats and Special Pathogens, WHO Collaborating Centre for Emerging Infections and Biological Threats, Highly Pathogenic Viruses, German Consultant Laboratory for Poxviruses, Robert Koch Institute, Seestraße 10, 13353, Berlin, Germany
| | - Katharina Pape
- Centre for Biological Threats and Special Pathogens, WHO Collaborating Centre for Emerging Infections and Biological Threats, Highly Pathogenic Viruses, German Consultant Laboratory for Poxviruses, Robert Koch Institute, Seestraße 10, 13353, Berlin, Germany
| | - Daniel Bourquain
- Centre for Biological Threats and Special Pathogens, WHO Collaborating Centre for Emerging Infections and Biological Threats, Highly Pathogenic Viruses, German Consultant Laboratory for Poxviruses, Robert Koch Institute, Seestraße 10, 13353, Berlin, Germany
| | - Andrea Thürmer
- Genome Sequencing and Genomic Epidemiology, Methodology and Research Infrastructure, Robert Koch Institute, Seestraße 10, 13353, Berlin, Germany
| | - Janine Michel
- Centre for Biological Threats and Special Pathogens, WHO Collaborating Centre for Emerging Infections and Biological Threats, Highly Pathogenic Viruses, German Consultant Laboratory for Poxviruses, Robert Koch Institute, Seestraße 10, 13353, Berlin, Germany
| | - Lars Schaade
- Centre for Biological Threats and Special Pathogens, WHO Collaborating Centre for Emerging Infections and Biological Threats, Highly Pathogenic Viruses, German Consultant Laboratory for Poxviruses, Robert Koch Institute, Seestraße 10, 13353, Berlin, Germany
| | - Andreas Nitsche
- Centre for Biological Threats and Special Pathogens, WHO Collaborating Centre for Emerging Infections and Biological Threats, Highly Pathogenic Viruses, German Consultant Laboratory for Poxviruses, Robert Koch Institute, Seestraße 10, 13353, Berlin, Germany
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Molteni C, Forni D, Cagliani R, Arrigoni F, Pozzoli U, De Gioia L, Sironi M. Selective events at individual sites underlie the evolution of monkeypox virus clades. Virus Evol 2023; 9:vead031. [PMID: 37305708 PMCID: PMC10256197 DOI: 10.1093/ve/vead031] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 03/31/2023] [Accepted: 05/12/2023] [Indexed: 06/13/2023] Open
Abstract
In endemic regions (West Africa and the Congo Basin), the genetic diversity of monkeypox virus (MPXV) is geographically structured into two major clades (Clades I and II) that differ in virulence and host associations. Clade IIb is closely related to the B.1 lineage, which is dominating a worldwide outbreak initiated in 2022. Lineage B.1 has however accumulated mutations of unknown significance that most likely result from apolipoprotein B mRNA editing catalytic polypeptide-like 3 (APOBEC3) editing. We applied a population genetics-phylogenetics approach to investigate the evolution of MPXV during historical viral spread in Africa and to infer the distribution of fitness effects. We observed a high preponderance of codons evolving under strong purifying selection, particularly in viral genes involved in morphogenesis and replication or transcription. However, signals of positive selection were also detected and were enriched in genes involved in immunomodulation and/or virulence. In particular, several genes showing evidence of positive selection were found to hijack different steps of the cellular pathway that senses cytosolic DNA. Also, a few selected sites in genes that are not directly involved in immunomodulation are suggestive of antibody escape or other immune-mediated pressures. Because orthopoxvirus host range is primarily determined by the interaction with the host immune system, we suggest that the positive selection signals represent signatures of host adaptation and contribute to the different virulence of Clade I and II MPXVs. We also used the calculated selection coefficients to infer the effects of mutations that define the predominant human MPXV1 (hMPXV1) lineage B.1, as well as the changes that have been accumulating during the worldwide outbreak. Results indicated that a proportion of deleterious mutations were purged from the predominant outbreak lineage, whose spread was not driven by the presence of beneficial changes. Polymorphic mutations with a predicted beneficial effect on fitness are few and have a low frequency. It remains to be determined whether they have any significance for ongoing virus evolution.
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Affiliation(s)
- Cristian Molteni
- Scientific Institute IRCCS E. MEDEA, Bioinformatics, Via don Luigi Monza, Bosisio Parini 23842, Italy
| | - Diego Forni
- Scientific Institute IRCCS E. MEDEA, Bioinformatics, Via don Luigi Monza, Bosisio Parini 23842, Italy
| | - Rachele Cagliani
- Scientific Institute IRCCS E. MEDEA, Bioinformatics, Via don Luigi Monza, Bosisio Parini 23842, Italy
| | - Federica Arrigoni
- Department of Biotechnology and Biosciences, University of Milan-Bicocca, Piazza della scienza, Milan 20126, Italy
| | - Uberto Pozzoli
- Scientific Institute IRCCS E. MEDEA, Bioinformatics, Via don Luigi Monza, Bosisio Parini 23842, Italy
| | - Luca De Gioia
- Department of Biotechnology and Biosciences, University of Milan-Bicocca, Piazza della scienza, Milan 20126, Italy
| | - Manuela Sironi
- Scientific Institute IRCCS E. MEDEA, Bioinformatics, Via don Luigi Monza, Bosisio Parini 23842, Italy
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Ullah M, Li Y, Munib K, Zhang Z. Epidemiology, host range, and associated risk factors of monkeypox: an emerging global public health threat. Front Microbiol 2023; 14:1160984. [PMID: 37213509 PMCID: PMC10196482 DOI: 10.3389/fmicb.2023.1160984] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 03/27/2023] [Indexed: 05/23/2023] Open
Abstract
Based on recent multiregional epidemiological investigations of Monkeypox (MPX), on 24 July 2022, the World Health Organization declared it a global public health threat. Retrospectively MPX was an ignored zoonotic endemic infection to tropical rainforest regions of Western and Central African rural communities until a worldwide epidemic in May 2022 verified the potential threat of monkeypox virus (MPXV) to be propagated across the contemporary world via transnational tourism and animal movements. During 2018-2022, different cases of MPX diagnosed in Nigerian travelers have been documented in Israel, the United Kingdom, Singapore, and the United States. More recently, on 27 September 2022, 66,000 MPX cases have been confirmed in more than 100 non-endemic countries, with fluctuating epidemiological footprinting from retrospective epidemics. Particular disease-associated risk factors fluctuate among different epidemics. The unpredicted appearance of MPX in non-endemic regions suggests some invisible transmission dynamic. Hence, broad-minded and vigilant epidemiological attention to the current MPX epidemic is mandatory. Therefore, this review was compiled to highlight the epidemiological dynamic, global host ranges, and associated risk factors of MPX, concentrating on its epidemic potential and global public health threat.
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Affiliation(s)
- Munib Ullah
- State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
- Department of Clinical Studies, Faculty of Veterinary and Animal Sciences, PMAS-Arid Agriculture University Rawalpindi, Rawalpindi, Pakistan
| | - Yanmin Li
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu, China
| | - Kainat Munib
- Department of Sociology, Allama Iqbal Open University Islamabad, Islamabad, Pakistan
| | - Zhidong Zhang
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu, China
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Chauhan RP, Fogel R, Limson J. Overview of Diagnostic Methods, Disease Prevalence and Transmission of Mpox (Formerly Monkeypox) in Humans and Animal Reservoirs. Microorganisms 2023; 11:1186. [PMID: 37317160 DOI: 10.3390/microorganisms11051186] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 04/26/2023] [Accepted: 04/28/2023] [Indexed: 06/16/2023] Open
Abstract
Mpox-formerly monkeypox-is a re-emerging zoonotic virus disease, with large numbers of human cases reported during multi-country outbreaks in 2022. The close similarities in clinical symptoms that Mpox shares with many orthopoxvirus (OPXV) diseases make its diagnosis challenging, requiring laboratory testing for confirmation. This review focuses on the diagnostic methods used for Mpox detection in naturally infected humans and animal reservoirs, disease prevalence and transmission, clinical symptoms and signs, and currently known host ranges. Using specific search terms, up to 2 September 2022, we identified 104 relevant original research articles and case reports from NCBI-PubMed and Google Scholar databases for inclusion in the study. Our analyses observed that molecular identification techniques are overwhelmingly being used in current diagnoses, especially real-time PCR (3982/7059 cases; n = 41 studies) and conventional PCR (430/1830 cases; n = 30 studies) approaches being most-frequently-used to diagnose Mpox cases in humans. Additionally, detection of Mpox genomes, using qPCR and/or conventional PCR coupled to genome sequencing methods, offered both reliable detection and epidemiological analyses of evolving Mpox strains; identified the emergence and transmission of a novel clade 'hMPXV-1A' lineage B.1 during 2022 outbreaks globally. While a few current serologic assays, such as ELISA, reported on the detection of OPXV- and Mpox-specific IgG (891/2801 cases; n = 17 studies) and IgM antibodies (241/2688 cases; n = 11 studies), hemagglutination inhibition (HI) detected Mpox antibodies in human samples (88/430 cases; n = 6 studies), most other serologic and immunographic assays used were OPXV-specific. Interestingly, virus isolation (228/1259 cases; n = 24 studies), electron microscopy (216/1226 cases; n = 18 studies), and immunohistochemistry (28/40; n = 7 studies) remain useful methods of Mpox detection in humans in select instances using clinical and tissue samples. In animals, OPXV- and Mpox-DNA and antibodies were detected in various species of nonhuman primates, rodents, shrews, opossums, a dog, and a pig. With evolving transmission dynamics of Mpox, information on reliable and rapid detection methods and clinical symptoms of disease is critical for disease management.
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Affiliation(s)
- Ravendra P Chauhan
- Biotechnology Innovation Centre, Rhodes University, Makhanda 6139, Eastern Cape, South Africa
| | - Ronen Fogel
- Biotechnology Innovation Centre, Rhodes University, Makhanda 6139, Eastern Cape, South Africa
| | - Janice Limson
- Biotechnology Innovation Centre, Rhodes University, Makhanda 6139, Eastern Cape, South Africa
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Falendysz EA, Lopera JG, Rocke TE, Osorio JE. Monkeypox Virus in Animals: Current Knowledge of Viral Transmission and Pathogenesis in Wild Animal Reservoirs and Captive Animal Models. Viruses 2023; 15:905. [PMID: 37112885 PMCID: PMC10142277 DOI: 10.3390/v15040905] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/24/2023] [Accepted: 03/27/2023] [Indexed: 04/03/2023] Open
Abstract
Mpox, formerly called monkeypox, is now the most serious orthopoxvirus (OPXV) infection in humans. This zoonotic disease has been gradually re-emerging in humans with an increasing frequency of cases found in endemic areas, as well as an escalating frequency and size of epidemics outside of endemic areas in Africa. Currently, the largest known mpox epidemic is spreading throughout the world, with over 85,650 cases to date, mostly in Europe and North America. These increased endemic cases and epidemics are likely driven primarily by decreasing global immunity to OPXVs, along with other possible causes. The current unprecedented global outbreak of mpox has demonstrated higher numbers of human cases and greater human-to-human transmission than previously documented, necessitating an urgent need to better understand this disease in humans and animals. Monkeypox virus (MPXV) infections in animals, both naturally occurring and experimental, have provided critical information about the routes of transmission; the viral pathogenicity factors; the methods of control, such as vaccination and antivirals; the disease ecology in reservoir host species; and the conservation impacts on wildlife species. This review briefly described the epidemiology and transmission of MPXV between animals and humans and summarizes past studies on the ecology of MPXV in wild animals and experimental studies in captive animal models, with a focus on how animal infections have informed knowledge concerning various aspects of this pathogen. Knowledge gaps were highlighted in areas where future research, both in captive and free-ranging animals, could inform efforts to understand and control this disease in both humans and animals.
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Affiliation(s)
| | | | - Tonie E. Rocke
- U.S. Geological Survey, National Wildlife Health Center, Madison, WI 53711, USA
| | - Jorge E. Osorio
- Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA
- Global Health Institute, University of Wisconsin, Madison, WI 53706, USA
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Forni D, Molteni C, Cagliani R, Sironi M. Geographic Structuring and Divergence Time Frame of Monkeypox Virus in the Endemic Region. J Infect Dis 2023; 227:742-751. [PMID: 35831941 PMCID: PMC10044091 DOI: 10.1093/infdis/jiac298] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 07/08/2022] [Accepted: 07/12/2022] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Monkeypox is an emerging zoonosis endemic to Central and West Africa. Monkeypox virus (MPXV) is genetically structured in 2 major clades (clades 1 and 2/3), but its evolution is poorly explored. METHODS We retrieved MPXV genomes from public repositories and we analyzed geographic patterns using STRUCTURE. Molecular dating was performed using a using a Bayesian approach. RESULTS We show that the population transmitted in West Africa (clades 2/3) experienced limited drift. Conversely, clade 1 (transmitted in the Congo Basin) possibly underwent a bottleneck or founder effect. Depending on the model used, we estimated that the 2 clades separated ∼560-860 (highest posterior density: 450-960) years ago, a period characterized by expansions and contractions of rainforest areas, possibly creating the ecological conditions for the MPXV reservoir(s) to migrate. In the Congo Basin, MPXV diversity is characterized by 4 subpopulations that show no geographic structuring. Conversely, clades 2/3 are spatially structured with 2 populations located West and East of the Dahomey Gap. CONCLUSIONS The distinct histories of the 2 clades may derive from differences in MPXV ecology in West and Central Africa.
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Affiliation(s)
- Diego Forni
- Bioinformatics, Scientific Institute IRCCS E. MEDEA, Bosisio Parini, Italy
| | - Cristian Molteni
- Bioinformatics, Scientific Institute IRCCS E. MEDEA, Bosisio Parini, Italy
| | - Rachele Cagliani
- Bioinformatics, Scientific Institute IRCCS E. MEDEA, Bosisio Parini, Italy
| | - Manuela Sironi
- Bioinformatics, Scientific Institute IRCCS E. MEDEA, Bosisio Parini, Italy
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Identifying the Most Probable Mammal Reservoir Hosts for Monkeypox Virus Based on Ecological Niche Comparisons. Viruses 2023; 15:v15030727. [PMID: 36992436 PMCID: PMC10057484 DOI: 10.3390/v15030727] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 03/07/2023] [Accepted: 03/08/2023] [Indexed: 03/16/2023] Open
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 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.
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Cohn H, Bloom N, Cai G, Clark J, Tarke A, Bermúdez-González MC, Altman D, Lugo LA, Lobo FP, Marquez S, Chen JQ, Ren W, Qin L, Crotty S, Krammer F, Grifoni A, Sette A, Simon V, Coelho CH. Mpox vaccine and infection-driven human immune signatures. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.03.07.23286701. [PMID: 36945651 PMCID: PMC10029032 DOI: 10.1101/2023.03.07.23286701] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/11/2023]
Abstract
Background Mpox (formerly known as monkeypox) outbreaks outside endemic areas peaked in July 2022, infecting > 85,000 people and raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side effects than previous smallpox vaccines and demonstrated efficacy against mpox infection in humans. Comparing JYNNEOS vaccine- and mpox-induced immunity is imperative to evaluate JYNNEOS' immunogenicity and inform vaccine administration and design. Methods We examined the polyclonal serum (ELISA) and single B cell (heavy chain gene and transcriptome data) antibody repertoires and T cells (AIM and ICS assays) induced by the JYNNEOS vaccine as well as mpox infection. Findings Gene-level plasmablast and antibody responses were negligible and JYNNEOS vaccinee sera displayed minimal binding to recombinant mpox proteins and native proteins from the 2022 outbreak strain. In contrast, recent mpox infection (within 20-102 days) induced robust serum antibody responses to A29L, A35R, A33R, B18R, and A30L, and to native mpox proteins, compared to vaccinees. JYNNEOS vaccine recipients presented comparable CD4 and CD8 T cell responses against orthopox peptides to those observed after mpox infection. Interpretation JYNNEOS immunization does not elicit a robust B cell response, and its immunogenicity may be mediated by T cells. Funding Research reported in this publication was supported, in part, by the National Cancer Institute of the National Institutes of Health under Award Number U54CA267776, U19AI168631(VS), as well as institutional funds from the Icahn School of Medicine.
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Hakim MS, Widyaningsih SA. The recent re-emergence of human monkeypox: Would it become endemic beyond Africa? J Infect Public Health 2023; 16:332-340. [PMID: 36680848 PMCID: PMC9846899 DOI: 10.1016/j.jiph.2023.01.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 01/11/2023] [Accepted: 01/15/2023] [Indexed: 01/19/2023] Open
Abstract
Viral outbreaks still become global health challenges, for instance, influenza A viruses, Japanese encephalitis, Ebola virus, Yellow fever, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since 7 May 2022, another outbreak of monkeypox also has been reported in European countries and the United States. Meanwhile, the monkeypox virus is previously endemic only in the western and central parts of Africa. Monkeypox is a zoonotic disease, although the primary animal reservoir remains unknown. This article concisely reviews the monkeypox virus, its transmission, pathogenesis, and clinical manifestation, its changing global epidemiology before and during the current outbreak, and possible driving factors of the recent outbreak. Furthermore, we also discuss whether the monkeypox virus would become endemic beyond Africa. Even though the available data suggests that human-to-human transmission is currently happening and unconnected clusters exist, many efforts have been made to tackle this outbreak, such as active case detection, contact tracing, isolation, and postexposure vaccination.
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Affiliation(s)
- Mohamad S Hakim
- Department of Microbiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; Center for Child Health - PRO, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Suci A Widyaningsih
- Center for Child Health - PRO, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
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Orthopoxvirus Zoonoses—Do We Still Remember and Are Ready to Fight? Pathogens 2023; 12:pathogens12030363. [PMID: 36986285 PMCID: PMC10052541 DOI: 10.3390/pathogens12030363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 02/13/2023] [Accepted: 02/16/2023] [Indexed: 02/24/2023] Open
Abstract
The eradication of smallpox was an enormous achievement due to the global vaccination program launched by World Health Organization. The cessation of the vaccination program led to steadily declining herd immunity against smallpox, causing a health emergency of global concern. The smallpox vaccines induced strong, humoral, and cell-mediated immune responses, protecting for decades after immunization, not only against smallpox but also against other zoonotic orthopoxviruses that now represent a significant threat to public health. Here we review the major aspects regarding orthopoxviruses’ zoonotic infections, factors responsible for viral transmissions, as well as the emerging problem of the increased number of monkeypox cases recently reported. The development of prophylactic measures against poxvirus infections, especially the current threat caused by the monkeypox virus, requires a profound understanding of poxvirus immunobiology. The utilization of animal and cell line models has provided good insight into host antiviral defenses as well as orthopoxvirus evasion mechanisms. To survive within a host, orthopoxviruses encode a large number of proteins that subvert inflammatory and immune pathways. The circumvention of viral evasion strategies and the enhancement of major host defenses are key in designing novel, safer vaccines, and should become the targets of antiviral therapies in treating poxvirus infections.
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Zandi M, Shafaati M, Shapshak P, Hashemnia SMR. Monkeypox virus replication underlying circadian rhythm networks. J Neurovirol 2023; 29:1-7. [PMID: 36719593 PMCID: PMC9888333 DOI: 10.1007/s13365-023-01118-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 01/11/2023] [Accepted: 01/21/2023] [Indexed: 02/01/2023]
Abstract
The mammalian brain has an endogenous central circadian clock that regulates central and peripheral cellular activities. At the molecular level, this day-night cycle induces the expression of upstream and downstream transcription factors that influence the immune system and the severity of viral infections over time. In addition, there are also circadian effects on host tolerance pathways. This stimulates adaptation to normal changes in environmental conditions and requirements (including light and food). These rhythms influence the pharmacokinetics and efficacy of therapeutic drugs and vaccines. The importance of circadian systems in regulating viral infections and the host response to viruses is currently of great importance for clinical management. With the knowledge gained from the COVID-19 pandemic, it is important to address any outbreak of viral infection that could become endemic and to quickly focus research on any knowledge gaps. For example, responses to booster vaccination COVID-19 may have different time-dependent patterns during circadian cycles. There may be a link between reactivation of latently infected viruses and regulation of circadian rhythms. In addition, mammals may show different seasonal antiviral responses in winter and summer. This article discusses the importance of the host circadian clock during monkeypox infection and immune system interactions.
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Affiliation(s)
- Milad Zandi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
| | - Maryam Shafaati
- Department of Microbiology, Faculty Science, Jahrom Branch, Islamic Azad University, Jahrom, Iran
| | - Paul Shapshak
- Global Disease Institute, Tampa General Hospital, Division of Infectious Diseases and International Health, Department of Internal Medicine, Morsani College of Medicine, Tampa, FL, USA
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Li K, Yuan Y, Jiang L, Liu Y, Liu Y, Zhang L. Animal host range of mpox virus. J Med Virol 2023; 95:e28513. [PMID: 36661039 DOI: 10.1002/jmv.28513] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 01/11/2023] [Accepted: 01/14/2023] [Indexed: 01/21/2023]
Abstract
Mpox is caused by the mpox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. Animal hosts, such as African rodents, mice, prairie dogs, and non-human primates, play important roles in the development and transmission of outbreaks. Laboratory animal infection experiments have demonstrated that some animals are susceptible to mpox virus. This review summarizes the current progress on the animal hosts for mpox virus. The surveillance of mpox virus in animal hosts will provide important insights into virus tracing, analysis of mutation evolutionary patterns, transmission mechanisms, and development of control measures.
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Affiliation(s)
- Kangxin Li
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yupei Yuan
- Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Lu Jiang
- Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yuwen Liu
- Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yihan Liu
- Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Leiliang Zhang
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
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Tiwari A, Adhikari S, Kaya D, Islam MA, Malla B, Sherchan SP, Al-Mustapha AI, Kumar M, Aggarwal S, Bhattacharya P, Bibby K, Halden RU, Bivins A, Haramoto E, Oikarinen S, Heikinheimo A, Pitkänen T. Monkeypox outbreak: Wastewater and environmental surveillance perspective. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 856:159166. [PMID: 36202364 PMCID: PMC9534267 DOI: 10.1016/j.scitotenv.2022.159166] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/22/2022] [Accepted: 09/28/2022] [Indexed: 04/13/2023]
Abstract
Monkeypox disease (MPXD), a viral disease caused by the monkeypox virus (MPXV), is an emerging zoonotic disease endemic in some countries of Central and Western Africa but seldom reported outside the affected region. Since May 2022, MPXD has been reported at least in 74 countries globally, prompting the World Health Organization to declare the MPXD outbreak a Public Health Emergency of International Concern. As of July 24, 2022; 92 % (68/74) of the countries with reported MPXD cases had no historical MPXD case reports. From the One Health perspective, the spread of MPXV in the environment poses a risk not only to humans but also to small mammals and may, ultimately, spread to potent novel host populations. Wastewater-based surveillance (WBS) has been extensively utilized to monitor communicable diseases, particularly during the ongoing COVID-19 pandemic. It helped in monitoring infectious disease caseloads as well as specific viral variants circulating in communities. The detection of MPXV DNA in lesion materials (e.g. skin, vesicle fluid, crusts), skin rashes, and various body fluids, including respiratory and nasal secretions, saliva, urine, feces, and semen of infected individuals, supports the possibility of using WBS as an early proxy for the detection of MPXV infections. WBS of MPXV DNA can be used to monitor MPXV activity/trends in sewerage network areas even before detecting laboratory-confirmed clinical cases within a community. However, several factors affect the detection of MPXV in wastewater including, but not limited to, routes and duration time of virus shedding by infected individuals, infection rates in the relevant affected population, environmental persistence, the processes and analytical sensitivity of the used methods. Further research is needed to identify the key factors that impact the detection of MPXV biomarkers in wastewater and improve the utility of WBS of MPXV as an early warning and monitoring tool for safeguarding human health. In this review, we shortly summarize aspects of the MPXV outbreak relevant to wastewater monitoring and discuss the challenges associated with WBS.
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Affiliation(s)
- Ananda Tiwari
- Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Finland; Department of Health Security, Expert Microbiology Research Unit, Finnish Institute for Health and Welfare, Finland.
| | - Sangeet Adhikari
- Biodesign Center for Environmental Health Engineering, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA
| | - Devrim Kaya
- School of Chemical, Biological, and Environmental Engineering, Oregon State University (OSU), Corvallis, OR, USA
| | - Md Aminul Islam
- COVID-19 Diagnostic Laboratory, Department of Microbiology, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh; Advanced Molecular Laboratory, Department of Microbiology, President Abdul Hamid Medical College, Karimganj, Kishoreganj, Bangladesh
| | - Bikash Malla
- Interdisciplinary Center for River Basin Environment, University of Yamanashi, 4-3-11 Takeda, Kofu, Yamanashi 400-8511, Japan
| | - Samendra P Sherchan
- Department of Biology, Morgan State University, Baltimore, MD, USA; Department of Environmental Health Sciences, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA
| | - Ahmad I Al-Mustapha
- Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Finland; Department of Veterinary Public Health and Preventive Medicine, Faculty of Veterinary Medicine, University of Ibadan, Oyo State, Nigeria; Department of Veterinary Services, Kwara State Ministry of Agriculture and Rural Development, Ilorin, Kwara State, Nigeria
| | - Manish Kumar
- Sustainability Cluster, School of Engineering, University of Petroleum & Energy Studies, Dehradun, Uttarakhand 248007, India
| | - Srijan Aggarwal
- Department of Civil, Geological and Environmental Engineering, College of Engineering and Mines, University of Alaska Fairbanks, PO Box 755900, Fairbanks, AK 99775, USA
| | - Prosun Bhattacharya
- Department of Sustainable Development, Environmental Science and Engineering, KTH Royal Institute of Technology, SE-10044 Stockholm, Sweden
| | - Kyle Bibby
- Department of Civil and Environmental Engineering and Earth Sciences, University of Notre Dame, IN 46556, USA
| | - Rolf U Halden
- Biodesign Center for Environmental Health Engineering, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA
| | - Aaron Bivins
- Department of Civil & Environmental Engineering, Louisiana State University, LA, USA
| | - Eiji Haramoto
- Interdisciplinary Center for River Basin Environment, University of Yamanashi, 4-3-11 Takeda, Kofu, Yamanashi 400-8511, Japan
| | - Sami Oikarinen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Annamari Heikinheimo
- Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Finland; Finnish Food Authority, Seinäjoki, Finland
| | - Tarja Pitkänen
- Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Finland; Department of Health Security, Expert Microbiology Research Unit, Finnish Institute for Health and Welfare, Finland
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Diatta KLES, Faye O, Sall AA, Faye O, Faye M. Useful public health countermeasures to control the current multicountry outbreak of Monkeypox disease. Front Public Health 2023; 10:1060678. [PMID: 36711326 PMCID: PMC9878340 DOI: 10.3389/fpubh.2022.1060678] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 12/21/2022] [Indexed: 01/15/2023] Open
Abstract
Monkeypox is a viral disease endemic to some countries in Central and Western Africa. However, sporadic human cases have also been reported outside of Africa. The first human case was reported in 1970 in the Democratic Republic of Congo. Very similar to the eradicated smallpox regarding its clinical representation, the Monkeypox disease is most common in children aged between 5 and 9 years with a fatality rate ranging from 1 to 11% in Africa. During the past decade, the number of countries that reported human cases of the disease grew significantly, while experts still sought knowledge on the characteristics of the virus. The recent increase in Monkeypox cases in many countries raises the concern about a possible global health threat. There is a need to subsequently provide insights into the incidence of Monkeypox disease and come up with mechanisms to prevent its emergence and contain its spread. Furthermore, it is crucial to have a better view of the global diagnostic capacity of the Monkeypox virus. This review aims to assess useful public health countermeasures to control the current multicountry outbreak of Monkeypox disease. Articles were searched in PubMed and Google Scholar electronic databases on 30 June 2022, using selected keywords, without language and date restriction. A total of 44 scientific records were published between 1 January 1962 and 30 June 2022. Herein, we discuss the epidemiological and public health situation at a global scale, provide an updated overview and data of utility for a better understanding of knowledge and research gaps in the epidemiology of the Monkeypox disease, and give useful measures for controlling the current multicountry outbreak.
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Paniz-Mondolfi A, Guerra S, Muñoz M, Luna N, Hernandez MM, Patino LH, Reidy J, Banu R, Shrestha P, Liggayu B, Umeaku A, Chen F, Cao L, Patel A, Hanna A, Li S, Look A, Pagani N, Albrecht R, Pearl R, Garcia-Sastre A, Bogunovic D, Palacios G, Bonnier L, Cera F, Lopez H, Calderon Y, Eiting E, Mullen K, Shin SJ, Lugo LA, Urbina AE, Starks C, Koo T, Uychiat P, Look A, van Bakel H, Gonzalez-Reiche A, Betancourt AF, Reich D, Cordon-Cardo C, Simon V, Sordillo EM, Ramírez JD. Evaluation and validation of an RT-PCR assay for specific detection of monkeypox virus (MPXV). J Med Virol 2023; 95:e28247. [PMID: 36271493 DOI: 10.1002/jmv.28247] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/11/2022] [Accepted: 10/19/2022] [Indexed: 01/11/2023]
Abstract
Monkeypox virus (MPXV) is a zoonotic orthopoxvirus within the Poxviridae family. MPXV is endemic to Central and West Africa. However, the world is currently witnessing an international outbreak with no clear epidemiological links to travel or animal exposure and with ever-increasing numbers of reported cases worldwide. Here, we evaluated and validated a new, sensitive, and specific real-time PCR-assay for MPXV diagnosis in humans and compare the performance of this novel assay against a Food & Drug Administration-cleared pan-Orthopox RT-PCR assay. We determined specificity, sensitivity, and analytic performance of the PKamp™ Monkeypox Virus RT-PCR assay targeting the viral F3L-gene. In addition, we further evaluated MPXV-PCR-positive specimens by viral culture, electron microscopy, and viral inactivation assays. The limit of detection was established at 7.2 genome copies/reaction, and MPXV was successfully identified in 20 clinical specimens with 100% correlation against the reference method with 100% sensitivity and specificity. Our results demonstrated the validity of this rapid, robust, and reliable RT-PCR assay for specific and accurate diagnosis of MPXV infection in human specimens collected both as dry swabs and in viral transport media. This assay has been approved by NYS Department of Health for clinical use.
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Affiliation(s)
- Alberto Paniz-Mondolfi
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Susana Guerra
- Department of Preventive Medicine, Public Health and Microbiology, Universidad Autónoma de Madrid, Madrid, Spain
| | - Marina Muñoz
- Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia
| | - Nicolas Luna
- Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia
| | - Matthew M Hernandez
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Luz H Patino
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jason Reidy
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Radhika Banu
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Paras Shrestha
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Bernadette Liggayu
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Audrey Umeaku
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Feng Chen
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Liyong Cao
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Armi Patel
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Ayman Hanna
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Sunny Li
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Andy Look
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Nina Pagani
- Department of Biotechnology Laboratory Sciences, Valencia College, Orlando, Florida, USA
- Infectious Diseases Research Branch, Venezuelan Science Incubator and The Zoonosis and Emerging Pathogens Regional Collaborative Network, Cabudare, Lara, Venezuela
| | - Randy Albrecht
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Rebecca Pearl
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Adolfo Garcia-Sastre
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Dusan Bogunovic
- Department of Microbiology, Center for Inborn Errors of Immunity, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Gustavo Palacios
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Lucia Bonnier
- Department of Pathology and Laboratory Medicine, Mount Sinai Beth Israel, New York, New York, USA
| | - Freddy Cera
- Department of Pathology and Laboratory Medicine, Mount Sinai Beth Israel, New York, New York, USA
| | - Heidi Lopez
- Department of Pathology and Laboratory Medicine, Mount Sinai Beth Israel, New York, New York, USA
| | - Yvette Calderon
- Department of Emergency Medicine, Mount Sinai Beth Israel, New York, New York, USA
| | - Erick Eiting
- Department of Emergency Medicine, Mount Sinai Beth Israel, New York, New York, USA
| | - Karr Mullen
- Department of Emergency Medicine, Mount Sinai Beth Israel, New York, New York, USA
| | - Sangyoon Jason Shin
- Department of Medicine, Ambulatory Care, The Center for Transgender Medicine and Surgery (CTMS) of Mount Sinai, Mount Sinai Beth Israel, New York, New York, USA
| | - Luz Amarilis Lugo
- Division of Infectious Diseases, Institute for Advanced Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Antonio E Urbina
- Division of Infectious Diseases, Institute for Advanced Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Carlotta Starks
- Mount Sinai Institute for Advanced Medicine, Jack Martin Fund Clinic and Comprehensive Health Clinic, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Tonny Koo
- Laboratory of Medical Microbiology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Patricia Uychiat
- Department of Pathology and Laboratory Medicine, Mount Sinai West, New York, New York, USA
| | - Avery Look
- Cornell University College of Agriculture and Life Sciences, Ithaca, New York, USA
| | - Harm van Bakel
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Ana Gonzalez-Reiche
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Adolfo Firpo Betancourt
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - David Reich
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Carlos Cordon-Cardo
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Viviana Simon
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Center for Vaccine Research and Pandemic Preparedness (C-VARPP), Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Emilia M Sordillo
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Juan David Ramírez
- Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia
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Li H, Huang QZ, Zhang H, Liu ZX, Chen XH, Ye LL, Luo Y. The land-scape of immune response to monkeypox virus. EBioMedicine 2022; 87:104424. [PMID: 36584594 PMCID: PMC9797195 DOI: 10.1016/j.ebiom.2022.104424] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/11/2022] [Accepted: 12/06/2022] [Indexed: 12/29/2022] Open
Abstract
Human monkeypox is a viral zoonotic smallpox-like disease caused by the monkeypox virus (MPXV) and has become the greatest public health threat in the genus Orthopoxvirus after smallpox was eradicated. The host immune response to MPXV plays an essential role in disease pathogenesis and clinical manifestations. MPXV infection leads to skin lesions with the genital area as the main feature in the current outbreak and triggers a strong immune response that results in sepsis, deep tissue abscess, severe respiratory disease, and injuries to multiple immune organs. Emerging evidence shows that the immunopathogenesis of MPXV infection is closely associated with impaired NK-cell function, lymphopenia, immune evasion, increased antibodies, increased blood monocytes and granulocytes, cytokine storm, inhibition of the host complement system, and antibody-dependent enhancement. In this overview, we discuss the immunopathology and immunopathogenesis of monkeypox to aid the development of novel immunotherapeutic strategies against monkeypox.
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Affiliation(s)
- Heng Li
- Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing, 400044, PR China
| | - Qi-Zhao Huang
- Provincial Key Laboratory of Immune Regulation and Immunotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China
| | - Hong Zhang
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 250033, Jinan, Shandong, China
| | - Zhen-Xing Liu
- Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing, 400044, PR China
| | - Xiao-Hui Chen
- Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing, 400044, PR China
| | - Li-Lin Ye
- Institute of Immunology, Third Military Medical University, Chongqing, 400038, PR China,Corresponding author: Institute of Immunology, Third Military Medical University, Chongqing, 400038, PR China.
| | - Yang Luo
- College of Life Sciences and Laboratory Medicine, Kunming Medical University, Kunming, Yunnan, 650500, PR China,Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan, 650118, PR China,Department of Laboratory Medicine, Jiangjin Hospital, Chongqing University, Chongqing, 402260, PR China,Corresponding author: College of Life Sciences and Laboratory Medicine, Kunming Medical University, Kunming, Yunnan, 650500, PR China.
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50
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Shen-Gunther J, Cai H, Wang Y. A Customized Monkeypox Virus Genomic Database (MPXV DB v1.0) for Rapid Sequence Analysis and Phylogenomic Discoveries in CLC Microbial Genomics. Viruses 2022; 15:40. [PMID: 36680080 PMCID: PMC9861985 DOI: 10.3390/v15010040] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 12/20/2022] [Indexed: 12/25/2022] Open
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 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.
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Affiliation(s)
- Jane Shen-Gunther
- Department of Clinical Investigation, Gynecologic Oncology & Clinical Investigation, Brooke Army Medical Center, Fort Sam Houston, TX 78234, USA
| | - Hong Cai
- Department of Molecular Microbiology and Immunology, University of Texas at San Antonio, San Antonio, TX 78249, USA
- South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, TX 78249, USA
| | - Yufeng Wang
- Department of Molecular Microbiology and Immunology, University of Texas at San Antonio, San Antonio, TX 78249, USA
- South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, TX 78249, USA
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