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Viruses
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Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen
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Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 1 March 2025 | Viewed by 10244

Special Issue Editors

Dr. David A. Schwartz

E-Mail Website
Guest Editor
Perinatal Pathology Consulting, Atlanta, GA, USA
Interests: perinatal, placental and obstetrical pathology; emerging infectious diseases; global maternal & child health; tropical medicine; pregnancy complications; stillbirth; maternal and infant mortality; medical epidemiology; medical anthropology
Special Issues, Collections and Topics in MDPI journals
Dr. Robert Colebunders

E-Mail Website
Guest Editor
Global Health Institute, University of Antwerp, Antwerp, Belgium
Interests: onchocerciasis; epilepsy; epidemiology; public health; infectious and tropical diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Patrick Katoto

E-Mail Website
Guest Editor
Centre for Tropical Diseases and Global Health, Catholic University of Bukavu, Bukavu, Democratic Republic of Congo
Interests: clinical trials; vaccinology; tropical medicine; sepsis; epidemiology; global health infection

Special Issue Information

Dear Colleagues,

The monkeypox virus (MPXV) has become the most potentially lethal member of the family Poxviridae since the eradication of its close relative, the smallpox virus (variola virus, VARV), in 1977. Since its first identification as a human pathogen in the Democratic Republic of the Congo (DRC) in 1970, mpox (monkeypox) has caused sporadic clusters and small outbreaks of infection in the endemic areas of West and Central Africa caused by two genetically distinctive strains, or clades, termed Clade I and Clade II. Since then, the epidemiology and demographics of infection with the mpox virus (MPXV) have dramatically changed. There have been increasing numbers of individuals and outbreaks occurring, especially in the DRC, with escalating transmission by sexual contact, shifting from mostly affecting children to affecting adults, and with outbreaks outside of the endemic African countries. These changes were evident in the 2022 multi-country mpox outbreak that affected approximately 87,000 persons in 110 countries, mostly through sexual transmission among networks of gay, bisexual, and other men who have sex with men. This was caused by a newly described genetic variant of Clade II, termed Clade IIb. In December 2022, the DRC declared a national outbreak of mpox, followed in September 2023 by an outbreak in South Kivu Province, which has spread to other regions and is driven by sexual transmission. Significantly, the South Kivu outbreak is associated with a novel strain of the Clade I MPXV that indicates adaptation to human transmission. This outbreak has confirmed that Clade I MPXV is especially dangerous when it occurs in pregnant women, demonstrating a fetal loss rate of 50 percent.

There are significant concerns in the medical and public health communities that mpox may become an even greater threat to global health in the near future. The present dangers of mpox are clear—the capability of human-to-human transmission via several routes, the lack of immunity within the global community, a natural wildlife reservoir, and multiple genetic variants that are adapting to a human host.

This Special Issue of Viruses will address a spectrum of topics on mpox and the MPXV including epidemiology, clinical features, molecular genetics, immunology, virology, diagnosis, treatment, prevention, and vaccination. Articles describing the MPXV in natural animal hosts and experiment animal models of infection are welcomed. Submissions which discuss the infection among special groups, including immunocompromised persons, pregnant persons, children, and commercial sex workers, and its association with sexual transmission are encouraged. Submissions can be in the form of original research articles, reviews, communications, viewpoints, case reports, and editorials. Illustrative and graphic materials including photographs are encouraged when possible.

Submissions from investigators working in the endemic and outbreak areas are encouraged to contribute to this issue regardless of financial concerns—please contact Dr. Schwartz for more information.

Dr. David A. Schwartz
Dr. Robert Colebunders
Dr. Patrick Katoto
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • monkeypox
  • mpox
  • monkeypox virus
  • mpxv
  • poxvirus
  • Poxviridae
  • Africa
  • DR Congo
  • outbreak
  • epidemic
  • stillbirth
  • sexual transmission
  • vaccination
  • emerging infection

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Published Papers (7 papers)

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Research

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23 pages, 1403 KiB  
Article
Investigating Mpox Strain Dynamics Using Computational and Data-Driven Approaches
by Isaiah Oke Idisi, Kayode Oshinubi, Vigbe Benson Sewanu, Mukhtar Muhammed Yahaya, Oluwafemi Samson Olagbami and Helen Olaronke Edogbanya
Viruses 2025, 17(2), 154; https://doi.org/10.3390/v17020154 - 23 Jan 2025
Viewed by 524
Abstract
This study explores Mpox transmission dynamics using a mathematical and data-driven epidemiological model that incorporates two viral strains, Clade I and Clade II. The model includes transmission pathways between humans and mammals and divides the human population into susceptible, exposed, infectious, hospitalized, and [...] Read more.
This study explores Mpox transmission dynamics using a mathematical and data-driven epidemiological model that incorporates two viral strains, Clade I and Clade II. The model includes transmission pathways between humans and mammals and divides the human population into susceptible, exposed, infectious, hospitalized, and recovered groups. Weekly data from the WHO for Spain, Italy, Nigeria, and the DRC from 2022 to 2024 are used for model validation via non-linear least-squares fitting, with model performance assessed by Root Mean Squared Error (RMSE). We conduct time-series analysis to detect trends and anomalies in Mpox cases, with scenario simulations examining strain-specific transmission and the basic reproduction number (R0). The mathematical model fit is compared with two statistical model fits to emphasize the importance of developing a model that incorporates Mpox strain. Mathematical analysis confirms the model’s key properties, including positivity, boundedness, and equilibrium stability. Results underscore the importance of strain-specific dynamics and varying infection proportions for R0. This study combines mathematical rigor with empirical data to provide valuable insights into Mpox transmission and offers a framework for understanding multi-strain pathogens in diverse populations. Results from the simulation indicate that an increase in the effective contact rate leads to the dominance of the prevalent Mpox Clades in each country. Based on these findings, we recommend the implementation of strategies aimed at reducing the effective contact rate to control the spread of the virus strains. Full article
(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)
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12 pages, 1908 KiB  
Article
Enhanced Immunogenicity and Affinity with A35R-Fc-Based Chimeric Protein Compared to MPXV A35R Protein
by Shimeng Bai, Yanxin Cui, Qibin Liao, Hongyang Yi, Zhonghui Liao, Gengwei Zhang, Fenfang Wu and Hongzhou Lu
Viruses 2025, 17(1), 116; https://doi.org/10.3390/v17010116 - 16 Jan 2025
Viewed by 474
Abstract
The re-emergence of the mpox pandemic poses considerable challenges to human health and societal development. There is an urgent need for effective prevention and treatment strategies against the mpox virus (MPXV). In this study, we focused on the A35R protein and created a [...] Read more.
The re-emergence of the mpox pandemic poses considerable challenges to human health and societal development. There is an urgent need for effective prevention and treatment strategies against the mpox virus (MPXV). In this study, we focused on the A35R protein and created a chimeric A35R-Fc protein by fusing the Fc region of IgG to its C-terminal. We then assessed its reactivity with A35R-specific antibodies and human convalescent plasma, as well as its immunogenicity. Our findings indicate that the A35R-Fc protein significantly enhances affinity to A35R antibodies compared to the commercially available A35R protein and exhibits considerable reactivity to human plasma. Additionally, mice immunized with A35R-Fc exhibited increased neutralizing antibody titers against the live MPXV. These results support the potential of Fc domain chimeric antigens as a strategy to enhance the efficacy of subunit vaccines targeting the MPXV. Full article
(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)
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17 pages, 9817 KiB  
Article
Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance
by Haydar Witwit, Beatrice Cubitt, Roaa Khafaji, Esteban M. Castro, Miguel Goicoechea, Maria M. Lorenzo, Rafael Blasco, Luis Martinez-Sobrido and Juan C. de la Torre
Viruses 2025, 17(1), 92; https://doi.org/10.3390/v17010092 - 13 Jan 2025
Viewed by 1173
Abstract
The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which [...] Read more.
The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which led the WHO to declare this mpox outbreak a public health emergency of international concern. The FDA-approved small molecule antiviral tecovirimat (TPOXX) is recommended to treat mpox cases with severe symptoms, but the limited efficacy of TPOXX and the emergence of TPOXX resistant MPXV variants has challenged this medical practice of care and highlighted the urgent need for alternative therapeutic strategies. In this study we have used vaccinia virus (VACV) as a surrogate of MPXV to assess the antiviral efficacy of combination therapy of TPOXX together with mycophenolate mofetil (MMF), an FDA-approved immunosuppressive agent that we have shown to inhibit VACV and MPXV, or the N-myristoyltransferase (NMT) inhibitor IMP-1088. Both MMF and IMP-1088 drugs exhibited strong dose-dependent antiviral activity against VACV and mpox, and potent synergistic effects in conjunction with TPOXX. Our findings support combination therapy of direct-acting (TPOXX) and host-targeted (MMF and IMP-1088) antivirals as a promising approach to treat mpox and prevent the emergence and spread of TPOXX-resistant MPXV variants. Full article
(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)
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Review

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14 pages, 520 KiB  
Review
Approaches to Next-Generation Capripoxvirus and Monkeypox Virus Vaccines
by Anna-Lise Williamson
Viruses 2025, 17(2), 186; https://doi.org/10.3390/v17020186 - 27 Jan 2025
Viewed by 472
Abstract
Globally, there are two major poxvirus outbreaks: mpox, caused by the monkeypox virus, and lumpy skin disease, caused by the lumpy skin disease virus. While vaccines for both diseases exist, there is a need for improved vaccines. The original vaccines used to eradicate [...] Read more.
Globally, there are two major poxvirus outbreaks: mpox, caused by the monkeypox virus, and lumpy skin disease, caused by the lumpy skin disease virus. While vaccines for both diseases exist, there is a need for improved vaccines. The original vaccines used to eradicate smallpox, which also protect from the disease now known as mpox, are no longer acceptable. This is mainly due to the risk of serious adverse events, particularly in HIV-positive people. The next-generation vaccine for mpox prevention is modified vaccinia Ankara, which does not complete the viral replication cycle in humans and, therefore, has a better safety profile. However, two modified vaccinia Ankara immunizations are needed to give good but often incomplete protection, and there are indications that the immune response will wane over time. A better vaccine that induces a long-lived response with only one immunization is desirable. Another recently available smallpox vaccine is LC16m8. While LC16m8 contains replicating vaccinia virus, it is a more attenuated vaccine than the original vaccines and has limited side effects. The commonly used lumpy skin disease vaccines are based on attenuated lumpy skin disease virus. However, an inactivated or non-infectious vaccine is desirable as the disease spreads into new territories. This article reviews novel vaccine approaches, including mRNA and subunit vaccines, to protect from poxvirus infection. Full article
(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)
10 pages, 248 KiB  
Review
Challenges in Global Distribution and Equitable Access to Monkeypox Vaccines
by Nengak P. Danladi, Progress Agboola, Peter Olaniyi, Solomon Eze, Oluwatimilehin Oladapo, Danielle Obiwulu, Olatokun Shamsudeen Akano, Olowoyeye Aishat Adeola, Khaliq Olawale, Azeez Idowu Adiatu and Agboola Peace
Viruses 2024, 16(12), 1815; https://doi.org/10.3390/v16121815 - 21 Nov 2024
Viewed by 1265
Abstract
The monkeypox outbreak has grown beyond the regions in which it was considered endemic. It has spread from central and west Africa to non-endemic regions like Europe, America, and other parts of the world. It has recently been classified as a public health [...] Read more.
The monkeypox outbreak has grown beyond the regions in which it was considered endemic. It has spread from central and west Africa to non-endemic regions like Europe, America, and other parts of the world. It has recently been classified as a public health emergency of international concern. This study evaluated the challenges faced globally and equitable access to monkeypox vaccines. Global competition has been observed in the race to obtain vaccines, with low- and middle-income countries being disadvantaged. Great inequity exists in the distribution of vaccines globally through advance purchase agreements, vaccine stockpiling, vaccine nationalism, the inequitable distribution of existing resources, and insufficient surveillance and reporting mechanisms. To address some of these challenges, there is a need for strengthening the global vaccine manufacturing capacity, targeting countries with elevated risk profiles and limited resources, strengthening surveillance systems, and addressing vaccine hesitancy. Full article
(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)
24 pages, 1400 KiB  
Review
Mpox Resurgence: A Multifaceted Analysis for Global Preparedness
by Fatouma Mohamed Abdoul-Latif, Ayoub Ainane, Houda Mohamed, Ali Merito Ali, Ibrahim Houmed Aboubaker, Pannaga Pavan Jutur and Tarik Ainane
Viruses 2024, 16(11), 1737; https://doi.org/10.3390/v16111737 - 5 Nov 2024
Viewed by 1670
Abstract
This study provides an in-depth analysis of mpox, encompassing its history, characteristics, epidemiology, diagnostics, treatment options, and the ongoing evolution of the virus and its transmission dynamics. Mpox, though once successfully eradicated, has re-emerged with new modes of transmission and a broader host [...] Read more.
This study provides an in-depth analysis of mpox, encompassing its history, characteristics, epidemiology, diagnostics, treatment options, and the ongoing evolution of the virus and its transmission dynamics. Mpox, though once successfully eradicated, has re-emerged with new modes of transmission and a broader host range. Genomic analyses have revealed the virus’s adaptability, posing challenges for diagnostics and vaccine efficacy. The epidemiology has shifted from sporadic zoonotic transmission in rural Africa to a significant presence in urban areas, particularly impacting high-risk populations. Advancements in diagnostics and therapeutics offer hope, but challenges persist. This work underscores the critical need for enhanced surveillance, vaccination strategies, and continued research to bolster global health systems and preparedness for future outbreaks. Full article
(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)
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Other

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9 pages, 696 KiB  
Commentary
Mpox in East Africa: Learning from COVID-19 and Ebola to Strengthen Public Health Responses
by Pierre Gashema, Tumusime Musafiri, Felix Ndahimana, Hyppolyte Iradukunda, Eric Saramba, Stuart T. Nyakatswau, Noel Gahamanyi, Patrick Gad Iradukunda, Ayman Ahmed, Tafadzwa Dzinamarira and Claude Mambo Muvunyi
Viruses 2024, 16(10), 1578; https://doi.org/10.3390/v16101578 - 8 Oct 2024
Cited by 3 | Viewed by 3280
Abstract
The Africa Centers for Disease Control and Prevention declared mpox a Public Health Emergency of Continental Security (PHECS) in Africa. African public health systems have moved to mobilize a response against a backdrop of inherent significant challenges. With this commentary, we discuss how [...] Read more.
The Africa Centers for Disease Control and Prevention declared mpox a Public Health Emergency of Continental Security (PHECS) in Africa. African public health systems have moved to mobilize a response against a backdrop of inherent significant challenges. With this commentary, we discuss how lessons from past public health emergencies, particularly COVID-19 and Ebola outbreaks, have prepared the region for improved disease surveillance, rapid response strategies, and effective public health communication and how these lessons can be applied to the mpox response, emphasizing the importance of strong healthcare infrastructure, effective data sharing, community engagement, targeted interventions, and robust contact tracing. Additionally, addressing misinformation and building public trust are crucial for controlling the spread of any disease. By leveraging these strategies, African countries can enhance their response to mpox. This includes improving diagnostic capabilities, strengthening cross-border collaborations, and prioritizing vaccination campaigns where needed. Ultimately, by applying the hard-earned lessons from the COVID-19 pandemic and Ebola outbreak, the East Africa region can better address the challenges posed by mpox and safeguard public health. Full article
(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)
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