Open Veterinary Journal, (2024), Vol. 14(12): 3144-3163

Review Article

10.5455/OVJ.2024.v14.i12.1

Navigating monkeypox: identifying risks and implementing solutions

Suhita Aryaloka¹, Aswin Rafif Khairullah², Muhammad Khaliim Jati Kusala², Ima Fauziah², Nanik Hidayatik^3*, Muhammad Agil⁴, M. Gandul Atik Yuliani³, Arindita Niatazya Novianti³, Ikechukwu Benjamin Moses⁵, Muhammad Thohawi Elziyad Purnama⁶, Syahputra Wibowo⁷, Kartika Afrida Fauzia^8,9, Ricadonna Raissa¹⁰, Abdul Hadi Furqoni¹¹, Mo Awwanah¹² and Katty Hendriana Priscilia Riwu¹³

¹Master Program of Veterinary Agribusiness, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

²Research Center for Veterinary Science, National Research and Innovation Agency (BRIN), Bogor, Indonesia

³Division of Basic Veterinary Medicine, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

⁴Division of Veterinary Clinic Reproduction and Pathology, School of Veterinary Medicine and Biomedical Sciences, IPB University, Bogor, Indonesia

⁵Department of Applied Microbiology, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria

⁶Department of Veterinary Science, Faculty of Health, Medicine, and Life Sciences, Universitas Airlangga, Banyuwangi, Indonesia

⁷Eijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Bogor, Indonesia

⁸Research Center for Preclinical and Clinical Medicine, National Research and Innovation Agency (BRIN), Bogor, Indonesia

⁹Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan

¹⁰Department of Pharmacology, Faculty of Veterinary Medicine, Universitas Brawijaya, Malang, Indonesia

¹¹Center for Biomedical Research, National Research and Innovation Agency (BRIN), Bogor, Indonesia

¹²Research Center for Applied Botany, National Research and Innovation Agency (BRIN), Bogor, Indonesia

¹³Department of Veterinary Public Health, Faculty of Veterinary Medicine, Universitas Pendidikan Mandalika, Mataram, Indonesia

*Corresponding Author: Nanik Hidayatik. Division of Basic Veterinary Medicine, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia. Email: nanik.h [at] fkh.unair.ac.id

Submitted: 05/08/2024 Accepted: 02/11/2024 Published: 31/12/2024

---

Abstract

Monkeypox is a zoonotic disease caused by the orthopox virus, a double-stranded DNA virus that belongs the Poxviridae virus family. It is known to infect both animals (especially monkeys and rodents) and humans and causes a rash similar to smallpox. Humans can become infected with monkeypox virus (MPXV) when they get in close contact with infected animals (zoonotic transmission) or other infected people (human-human transmission) through their body fluids such as mucus, saliva, or even skin sores. Frequently observed symptoms of this disease include fever, headaches, muscle aches, and a rash that initially looks like a tiny bump before becoming a lump that is filled with fluid. Monkeypox symptoms also include an incubation period of 5–21 days, divided into prodromal and eruption phases. Several contributing factors, such as smallpox vaccine discontinuation, widespread intake of infected animal products as a source of protein, and high population density, amongst others, have been linked to an increase in the frequency of monkeypox outbreaks. The best course of action for diagnosing individuals who may be suffering from active monkeypox is to collect a sample of skin from the lesion and perform PCR molecular testing. Monkeypox does not presently have a specific therapy; however, supportive care can assist in managing symptoms, such as medication to lower body temperature and pain. Three major orthopoxvirus vaccines have been approved to serve as a preventive measure against monkeypox: LC16, JYNNEOS, and ACAM2000. The discovery that the monkeypox outbreak is communicable both among humans and within a population has sparked new public health worries on the possibility of the outbreak of another viral pandemic. Research and studies are still being conducted to gain a deeper understanding of this zoonotic viral disease. This review is therefore focused on deciphering monkeypox, its etiology, pathogenesis, transmission, risk factors, and control.

Keywords: Monkeypox, Viral disease, Public health, Virus, Zoonosis.

---

Introduction

A zoonotic illness called monkeypox can infect both humans and animals and causes a rash similar to smallpox but with less severe symptoms (Zahmatyar et al., 2023). The orthopox virus that causes this disease is the monkeypox virus (MPXV) (Fig. 1) which is a member of the Poxviridae virus family (Shchelkunova and Shchelkunov, 2022). In 1958, this virus was discovered in primates housed in Denmark for scientific purposes (Ghosh et al., 2023). According to reports, the first human case occurred in the Democratic Republic of the Congo in 1970 (Masood et al., 2022). Several thousand human cases have been reported in periodic epidemics over the past 50 years, mostly in Africa (Li et al., 2022a). The 2022 outbreak of monkeypox, which affected numerous nations in both endemic and non-endemic regions, has garnered substantial global interest (Mitjà et al., 2023).

Infected animals including monkeys, rats, and squirrels can spread this illness to people (Ahmed et al., 2023a). Humans can contract this virus by coming into close contact with the bodily fluids of the carrier, such as mucus, saliva, or skin sores (Letafati and Sakhavarz, 2023). Symptoms of this illness include fever, headaches, muscle aches, and a rash that initially looks like a tiny bump before becoming a lump that is filled with fluid (Wang and Lun, 2023). Any area of the body can develop lumps from monkeypox (Fig. 2), although the face, hands, and feet are the most common places (Zahmatyar et al., 2023). Severe infections like this one could lead to potentially lethal consequences like pneumonia and sepsis (Rabaan et al., 2023).

The rise or increasing frequency of monkeypox outbreaks has been linked to many factors; among these is heightened vulnerability to monkeypox infection following smallpox vaccine discontinuation. It has been demonstrated that a smallpox vaccination can prevent monkeypox with an 85% success rate (Poland et al., 2022). The widespread intake of animal products as a source of protein may also be a contributing factor. This could serve as a reservoir for MPXV, particularly in areas affected by societal crises like civil war and poverty (Harapan et al., 2022). Other identified factors linked to monkeypox outbreaks are high population density, convenience of transportation, and ecological and environmental conditions (such as the clearance of tropical rainforests) that raise the danger of exposure to reservoir animals (Banuet-Martinez et al., 2023).

A recent study explored a nonlinear trend of the continuous model using a differential equation in the effective control of Monkeypox propagation/transmission by including some parameters such as vaccination, treatment, level of awareness, and quarantined infected individuals with severe complications as the main parameters (Kaushal and Sinha, 2024). This model will be very impactful in health policy-making and vaccination campaigns.

Monkeypox does not presently have a specific therapy; nevertheless, supportive care can assist in managing symptoms, such as medication to lower body temperature and pain (Karagoz et al., 2023). Those who are afflicted with this illness are mandated to self-quarantine by remaining at home and minimizing social interactions with others in their immediate surroundings (Luo and Han, 2022). It is advised that patients with severe symptoms check into a hospital to receive comprehensive care. Monkeypox can be prevented with the smallpox vaccine; however, it is not always successful (Poland et al., 2022). Avoiding direct contact with sick people and animals, as well as practicing good hygiene practices like frequent hand washing are the best ways to prevent contracting monkeypox (Khattak et al., 2023).

Fig. 1. Representative pictures of monkeypox [Source: World Health Organization (2024)].

Fig. 2. Representative structure of the MPXV (Source: petershcreiber.media).

The discovery that the monkeypox outbreak is communicable both among humans and within a population has sparked new worries about the possibility of a viral pandemic and issues with public health. Up till now, research and studies have been conducted to gain a deeper understanding of this illness. This review’s objective is to elucidate the etiology, history, epidemiology, pathogenesis, immune response, pathology, clinical symptoms, diagnosis, differential diagnosis, transmission, risk factors, treatment, vaccination, and control of monkeypox.

Etiology

The orthopox virus, which is a double-stranded DNA virus that causes monkeypox belongs to the same genus as cowpox, vaccinia, and variola, the smallpox vaccine’s causal agent (Shchelkunova and Shchelkunov, 2022). Brick-like virions measuring 200–250 nm are visible in electron microscopy of MPXV-infected cells; these virions are identical to those of the variola or vaccinia viruses (VAVCs) (Quarleri et al., 2022).

The MPXV genome is large, with about 200 kilobase pairs, and encodes about 190 proteins for building viral particles and modulating various host processes (Schwartz and Pittman, 2023). In the past, two separate groups of monkeypox have been found in different parts of Africa, with genome sequence differences of about 0.5% (Xiang and White, 2022). In Central Africa and the Congo Basin, clade 1 (which has a case fatality rate [CFR] of 1%–12%) is typically the cause of this sickness; in these regions, clade 2 which is less virulent and has a CFR of less than 0.1% is the primary cause of this illness on the African continent (Zahmatyar et al., 2023). Clade 1 and 2 viruses differ genomically in areas that encode crucial virulence genes, which could account for variations in clinical severity. For instance, clade 2 viral strains lack genes for complement control proteins which stop the complement pathway from starting. Similarly, clade 1 virus strains used in an animal model of monkeypox result in lower rates of morbidity and mortality in dogs when the complement control protein is deleted (Rosa et al., 2023).

In the 2022 worldwide monkeypox outbreak, a new B.1 lineage was discovered. Because of its strong kinship with clade 2, it was categorized as clade 2b (Mitjà et al., 2023). In contrast to RNA viruses, orthopoxviruses (OPXVs) have relatively stable double-stranded DNA and a modest mutation rate (one to two nucleotide changes per year) due to the proofreading exonuclease activity of their DNA polymerase (Sasani et al., 2018). The 2017 outbreak strains in Nigeria have been connected to the novel B.1 lineage; nonetheless, variations in up to 50 single nucleotide polymorphisms (mostly APOBEC3-related mutations) have been found, indicating a mutation rate 6–12 times higher than previously thought (Islam et al., 2023). Mutations of this kind imply widespread human-to-human transmission because APOBEC3, a human protein, introduces defects into the viral genome as a cellular defensive mechanism (Stenglein et al., 2010). What impact these differences have on MPXV virulence, adaptability, and transmission in people is one of the main concerns.

History

In 1970, the Democratic Republic of the Congo saw the first instance of monkeypox in a 9-month-old kid (Nyame et al., 2023). Following an epidemic in the US in 2003–2004, the virus gained widespread attention (Di Giulio and Eckburg, 2004). The clinical signs of smallpox and monkeypox are comparable after infection. Nonetheless, monkeypox rarely proves to be fatal. In the 1970s, after smallpox was eradicated, the incidence of the virus rose as a result of the smallpox vaccination campaigns ending, drawing more attention to the disease worldwide (Dou et al., 2023). Although primates are not the true carriers of this virus, the name was chosen based on early observations of the virus in monkeys. The precise origins of this virus are still unknown; however, it is thought to spread through a variety of rodents and small mammal species (Kaler et al., 2022). This virus was only known to arise in non-human hosts before 1970. Nevertheless, following the US outbreak in 2003, this view was altered. The 2003 monkeypox outbreak in the Americas revealed higher viremia levels in infected patients as well as higher rates of transmission among humans (Zahmatyar et al., 2023). Although outbreaks of monkeypox are currently predominantly recorded in the Western Hemisphere and Europe; historically, the majority of cases have been reported in Africa (Johri et al., 2022). Although the outbreak’s origin is still unknown, different research groups are attempting to track down its source through contact tracing initiatives.

Epidemiology

Since 1970, there have been reports of these instances in ten African nations. The country with the highest number of cases affected was Congo, where there were 38 in 1970–1979, 511 in 1990–1999, and 18,788 cases in 2010–2019. Nigeria had the second-highest number of cases (181), behind the Central African Republic (67 cases), and the Republic of Congo (97 cases) (Bunge et al., 2022). In excess of 90% of these cases, there was no prior history of smallpox vaccination. Between the 1970s and the 2010s, the average age of an infected person rose from 4 to 21 years old (Kulshrestha et al., 2022). The CFR aggregated together was 8.7%. The CFR of clade-1 infections, when broken down by clade was 10.6%, while the CFR of clade 2 infections was 3.6% (Islam et al., 2023). All deaths in the 1970s and 1990s occurred among those under the age of ten, while in the 2010s, deaths in this age group accounted for only 37.5% of all deaths (Hakim and Widyaningsih, 2023). The decreased immunity from the smallpox vaccination and the increased human penetration of sylvatic habitats are the causes of the increase in cases in Africa (Mungmunpuntipantip and Wiwanitkit, 2022). This increase in cases in Africa has been characterized in the literature for several years but has been largely ignored.

The first cases outside of Africa were documented in the US in 2003, when 53 individuals (mean age 26 years, range 4–53 years) contracted the West African clade from exotic animals in Ghana that had contaminated their pet dogs (Singhal et al., 2022). A total of 21% had been vaccinated against smallpox; no one died, but 26% of patients, including a 10-year-old child with encephalitis were admitted to hospitals. Several cases without fatalities were recorded in a number of countries between 2018 and 2021 (one in Singapore and seven in the UK); five of the victims were tourists returning from Nigeria (Chowdhury et al., 2022).

A case of monkeypox was also reported in the UK on May 6, 2022, affecting a traveler returning from Nigeria (Kumar et al., 2022). Ever since, the number of cases has skyrocketed and included individuals who had never visited an area where the disease was present before. From January 1, 2022, to July 22, 2022, 16,016 laboratory-confirmed cases of monkeypox and 5 fatalities were reported to the World Health Organization (WHO) from 75 regions (Zahmatyar et al., 2023). The United States (n=2,316), Germany (n=2,268), the United Kingdom (n=2,137), Spain (n=3,125), and Northern Ireland (n=2,137) are the five nations that reported the largest cumulative number of cases worldwide (Lai et al., 2022). Only 301 laboratory-confirmed cases were reported from the African region; however, they led to five deaths (Sah et al., 2022a). Nonetheless, 1400 cases and 63 deaths were reported by the African Surveillance Network in 2022 (Koenig et al., 2022). On July 23, 2022, the WHO designated monkeypox a public health emergency of international concern due to the growing number of cases reported globally (Zheng et al., 2022).

The median age of patients was 38 years (range 18–68 years) in a recently published multicountry study of 528 MPXV infections (527 men and 1 woman) across 5 continents and 16 countries between June 27, 2022, and June 24, 2022; 98% of infected people were gay or bisexual men, 75% were white, and 41% had HIV infection (Ortiz-Saavedra et al., 2022). Notably, the majority of people with HIV have undetectable viral levels and 95% of those infected are receiving antiretroviral medication. In 28% of instances, there was a history of international travel, and in 29% of cases, there were concurrent STDs. For 95% of patients, sexual activity is the primary means of transmission. Of the 32 males whose seminal fluid was examined in this study, MPXV DNA was found in 29 of them; it is unknown, though, if this is a virus that can replicate. A smallpox vaccination history was reported by 9% of research participants without any documented deaths (Ortiz-Saavedra et al., 2022).

Four cases of monkeypox were reported in four men in India on July 24, 2022; the first case was recorded on July 14, 2022 (Singhal et al., 2022). The last case from Delhi had no prior history of traveling abroad, in contrast to the preceding three cases from Kerala who had traveled abroad.

Changes in the biology of the virus, climate change, diminished immunity after smallpox vaccination, increased international travel after COVID-19 restrictions were lifted, and high-risk sexual behavior are all contributing factors to the resurgence of monkeypox in both endemic and non-endemic areas (Al-Musa et al., 2022). The MPXV virus responsible for the current outbreak, according to a phylogenetic study, is a member of clade 3, which is closely connected to the virus that occasionally caused cases in Maryland, USA in 2021, and also related to the clade 2 virus that caused the disease outbreak in Nigeria from 2017–2018 (Luna et al., 2022). All of the viruses involved in the present outbreak have genomic sequences that are tightly clustered and point to the outbreak’s genesis.

A recent study that captured the dynamics of monkeypox detailed a comprehensive numerical model leveraging fuzzy fractional differential equations for analyzing the disease transmission dynamics with high accuracy. This model explored how vaccination significantly curbs monkeypox spread (Venkatesh et al., 2024). The study highlights the importance and good impact of advanced mathematical tools in capturing the complex dynamics of monkeypox transmission; thus, paving the way for better effective control strategies.

Another new study employed a compartmental mathematical model that incorporated the impact of immunization, isolation, and hospitalization on disease management, as well as the interaction between humans and rodents in numerical simulations for the effective control of monkeypox transmission and management (Manivel et al., 2024).

Although this disease primarily affects adult homosexual men at the moment, it is expected to spread to women, children, and the general public in the future (Nagarajan et al., 2022). The danger of contracting this disease is higher for healthcare professionals. Concerns exist over human-animal transmission which may serve as a reservoir for recurring diseases.

Pathogenesis

The respiratory system or the skin are the two entry points for the MPXV into the human body (Upadhayay et al., 2022). The type of MPXV and its entrance point may have an impact on how the illness presents itself.

The MPXV can infect airway epithelial cells in the respiratory system, and it can infect keratinocytes, fibroblasts, and endothelial cells in the skin to cause cytopathic and productive infections (Lum et al., 2022). Moreover, the virus is abortively infected in antigen-presenting cells including dendritic cells, macrophages, and Langerhans cells (in the skin), which permits the virus to live long enough to transfer the antigen to the lymph nodes that drain blood (Zandi et al., 2023). Mature virions with a single lipid membrane are produced by viral replication, gene expression, and virion assembly in the cytoplasm of the host cell (Aljabali et al., 2022). These are released as extracellular virions with additional envelopes. These are two distinct antigenic types with either 6 (extracellular virions) or 25 (mature virions) surface proteins.

The virus that causes monkeypox travels from the original infection site to the lymph nodes by means of antigen-presenting cell migration and direct viral entry into lymphatic channels (Qudus et al., 2023). MPXV can target other major organs, such as the spleen and liver, where it enlarges and produces a second major wave of viremia. This allows the virus to multiply and spread further into the organs that are farther away, such as the lungs, kidneys, intestines, and skin, after initial replication in the lymph nodes results in low-level primary viremia (Chadha et al., 2022).

During the incubation period (until day 4 post-challenge) in the MPXV clade 1 model derived from the respiratory system of primates, the virus replicates in the respiratory epithelium. Subsequently, it spreads to regional lymph nodes and lymphoid organs, such as the tonsils, spleen, liver, and large intestine, which develop until day 6 (Hakim and Widyaningsih, 2023). After widespread sores on the skin and mucous membranes, the virus was finally found in the blood on day 8, and its concentrations continued to rise until day 10, based on a previous report (Parker and Buller, 2013). Large respiratory droplets were noted to be released by ulcerated sores in the mouth and throat which disseminate a lot of virus particles (Karagoz et al., 2023).

Following MPXV clade 2 infection, subcutaneous inoculation models in monkeys demonstrated limited skin and lymphatic system viral multiplication, indicating moderate and localized illness, based on a previous study (Saied et al., 2022). Following skin injection with MPXV clade 1, the respiratory, gastrointestinal, and genitourinary systems may be impacted (Li et al., 2024a). The only information available on human skin inoculation is from variolation, or vaccination against the vaccinia or variola viruses, which causes lesions that are localized to the site of entry. Similar to this, another study indicated that individuals who contracted the MPXV through sexual contact during the 2022 outbreak showed limited anogenital and oral lesions, and a few of them also had a few distant lesions (on the face, limbs, and trunk); nonetheless, large-scale and widespread skin lesions were uncommon (Lai et al., 2022).

Skin lesions in the vesicular stage might exhibit pronounced spongiosis, degeneration of bulging keratinocytes, dermal edema, and acute inflammation upon histopathological investigation (Schmidle et al., 2023). Rodríguez-Cuadrado et al. (2023) reported that only a small percentage of viable keratinocytes remain in the pustule stage, with the majority of the cells being inflammatory and remnants of apoptotic keratinocytes. Multinucleated or cytopathic damage, such as eosinophilic inclusion bodies, conspicuous nucleoli, and so-called ground glass chromatin could also be seen in viable keratinocytes (Rodríguez-Cuadrado et al., 2023). Immunochemistry revealed that all keratinocytes in the afflicted epidermis have the virus in their cytoplasm (but not in the unaffected epidermis) (Wang and Lun, 2023). T lymphocytes including CD4⁺ and CD8⁺ components predominate in lymphocytic infiltration (Saghazadeh and Rezaei, 2022).

Following a natural monkeypox infection or vaccination with the VAVC, the cellular immune response is typified by a fast increase of activated effector CD4⁺ and CD8⁺ T cells. This is followed by a decline in time, and the decline eventually returns to normal after 12–20 days from the onset of symptoms (Agrati et al., 2023). The majority of patients have certain T cells that may produce TNF, MCP-1, IL-1β, IL-6, IL-8, and other Th1 inflammatory cytokines (Zhang and An, 2007). Memory T cells have been observed to survive for up to 50 years (half-life 8–15 years) following VAVC vaccination; but as numerous cases of MPXV breakthroughs have demonstrated, this does not always confer robust protection against the virus (Jain et al., 2023). While CD8+ T cells eliminate virus-infected macrophages to stop the virus from spreading, effector CD4+ T cells help improve memory and B cell differentiation into antibody-secreting cells (Saghazadeh and Rezaei, 2022). Similar poxvirus-specific T cell responses are also indicated by high CD4⁺ T cell counts (>350 cells), while low CD4⁺ counts (<350 cells) are not well-studied (Agrati et al., 2023). In non-human primates that have received vaccinations, B cell responses are essential for immunity, while the loss of CD4⁺ or CD8⁺ T cells has minimal effect on disease prevention (Cohn et al., 2023). Nevertheless, it is troubling since CD4+ reduction before immunization reduces the generation of protective antibodies and B cell responses while also making infection more severe (Raccagni et al., 2024).

Immune response

Human MPXV infection is linked to markedly reduced levels of TNF-a, IFN-g, IL-2, and IL-12, and elevated levels of ILS, C-C motif chemokine ligand 2 (CCL2), and CCL5 (Alakunle et al., 2024). IgM and IgG antibodies are produced by MPXV infection, along with long-term remaining IgG memory B cells and a fast increase of activated CD4⁺ and CD8⁺ effector T cells that eventually diminish (Agrati et al., 2023). Additionally, by inhibiting T cell receptor-mediated T cell activation, MPXV impedes the antiviral CD8⁺ and CD4⁺ T cell responses of the adaptive immune system (Zandi et al., 2023).

The assumption, and in certain situations, the evidence suggests that MPXV uses comparable tactics to avoid the host’s immune system because of the strong homology between the genes of MPXV and the OPXV orthologs (Kumar et al., 2023). Toll-like receptors (TLRs) family are receptors that recognize patterns in molecular damage, such as viral double-strand breaks (dsRNA). Viral dsRNA binding to particular TLR members causes proinflammatory molecules to be expressed, which in turn activates the adaptive immune defense system and the host’s antiviral response (Hatmal et al., 2022). The TLR4 signaling pathway is inhibited by the VAVC A46 protein. The MPXV A47 homologue may or may not have the same characteristics, but the A47 protein is structurally similar to the VACV A52R protein, which inhibits the TLR3 and TLR4 signaling pathways, highlighting the MPXV A47’s function in blocking TLR signaling (Alakunle et al., 2024). Transcriptome study of MPXV-infected cells indicates suppression of TLR3 target genes, although it is unclear if MPXV creates low amounts of dsRNA intermediates that TLR3 can detect (Arndt et al., 2016). Additionally, dsRNA has the ability to activate kinase R (PKR), which phosphorylates eIF2a and prevents the translation of viral and cellular mRNAs (Bou-Nader et al., 2019). Since VACV E3 and K3 are PKR inhibitors, VACV can elude the effects of antiviral therapy. The VACV E3 protein’s N-terminal domain is necessary for interaction with dsRNA (White and Jacobs, 2012). The 37 aa truncation at the amino terminus of the MPXV F3 protein, which is a homolog of the VACV E3 protein, indicates that MPXV F3 does not bind dsRNA (Arndt et al., 2015). Though recombinant VACV expressing the MPXV F3L gene does not decrease host PKR activation, MPXV can inhibit the host immunological response. This implies that in the face of low antiviral efficacy, MPXV has evolved to encode a protein that has not yet been identified to make up for the loss of the N-terminal F3 amino acid (Shchelkunov, 2012). As previously noted, Clade II isolates of MPXV CCP (D14L gene) are completely lacking, while Clade I strains are expected to exhibit CCP, albeit with a shortened fourth short consensus repeat (Ghate et al., 2023). In rhesus macaques infected with MPXV, loss of CCP/MOPICE expression restricts the adaptive immune response (Domán et al., 2022).

One important innate immune response effector, interferon (IFN), has the ability to stop viral replication (Saadh et al., 2023). An inhibitor of secreted type I IFN, the MPXV B16 protein (ortholog of VACV B19) inhibits antiviral type I IFN-induced signaling pathways (Alakunle et al., 2024). IFN-regulated factor 3 (IRF3) is destabilized by VACV K7, which also inhibits NFκB activation to abrogate IFN signaling, whereas VACV H1 can prevent IFN signaling (Pilna et al., 2021). Although it is unclear if the MPXV orthologues D9 and H1 serve the same purpose, it is believed that both proteins interact with a number of immune system cellular proteins. VACV E3 binds to host Z-DNA binding protein 1 (ZBP1) and obstructs IFN signaling (Koehler et al., 2021). It is necessary to determine whether the MPXV E3 ortholog (F3) depends on ZBP1 to understand how it disrupts the IFN pathway. The IFN and NFκB pathways can be triggered by the cGAS/STING (cyclic GMP-AMP synthase/stimulator of IFN gene) DNA sensing receptor pathway (Skopelja-Gardner et al., 2022). VACV B16 and B8 proteins function as soluble IFN-a and IFN-g receptors to inhibit IFN signaling (Mann et al., 2008). MPXV functional homologues are encoded by ORFs B16R and B9R (Zhu et al., 2023). A toxin encoded by OPXV degrades 2′,3′ cGAMP, inhibiting cGAS/STING signaling in the process (Pan et al., 2023). MPXV stores doxin, which is fused with another C-terminal domain that was previously identified as having homology to the human schlafen protein (VACV B2R=MPXV B4R). As a result, MPXV targets the cGAS/STING pathway to avoid the immune system (Yi et al., 2024).

The antiviral cytokine TNFa and other immunomodulating molecules are targets that MPXV uses to elude the immune system (Lucena-Neto et al., 2023). The cytokine response modifying protein B (CrmB; J2L or OPG002) encoded by MPXV acts as a TNFa spoof receptor (Johnston et al., 2015). The chemokine ligands CCL25, CCL28, CXC 12 (CXCL12), CXCL13, and CXCL14 can all be bound by the C-terminal domain of VACV CrmB (Alejo et al., 2019). The homologous domains of MPXV CrmB have substantially different amino acid sequences, yet it is unknown if MPXV CrmB interacts with these chemokines.

The removal of viral infections is aided by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. In the peripheral blood and lymph nodes of rhesus macaques infected with MPXV, the number of NK cells increased dramatically. However, these cells’ ability to migrate was hindered, and their ability to express chemokine receptors (such as CCR5, CCR6, and CXCR3) and secrete IFNg and TNFa was compromised (Song et al., 2013). A cohort of mice whose low levels of NK cells made them extremely susceptible to infection with the CAST/EiJ mouse strain of OPXV was used to illustrate the significance of NK cells in managing MPXV viral load (Earl et al., 2020). Even when CD4⁺ and CD8⁺ T cells are low, IL-15 therapy protects CAST/EiJ mice from fatal MPXV infection because it is known to boost the frequency of NK cells and IFNg-secreting CD8⁺ T cells. This suggests that the protective effect is caused by NK cells that have grown.

The MPXV B10 protein interferes with peptide loading and MHC-I trafficking in the endoplasmic reticulum to prevent CTLs from identifying virus-infected cells (Alakunle et al., 2024). NK cells nevertheless continue to use NKG2D to screen cells for the lack of MHC-I, preventing any compromise of the MHC system. To evade identification by NK cells, MPXV-infected cells with downregulated MHC-I expression secrete the NKG2D-binding protein OCMP and inhibit NKG2D-dependent NK cell lysis in cells lacking MHC-I (Brandstadter and Yang, 2011). IFNg-inducing factor IL-18 increases chemokine and cytokine creation, controls Th1 and Th2 cell responses, and activates CTL and NK cells (Nakanishi et al., 2001). To inhibit IL-18 activity, OPXV produces an IL-18 binding protein. The IL-18 binding protein is encoded by the MPXV D6L gene (Chen et al., 2005).

The chemokine-binding proteins encoded by the MPXV J3R and A41L genes are thought to disrupt the gradient of chemokine concentration, causing a reduction in neutrophil migration in MPXV-infected tissues (Bahar et al., 2008). This, in turn, lessens the virulence of the virus and the inflammatory reactions it elicits.

In the early activation of MPXV infection in mice, the complement system is a vital component of the innate immune system and plays a vital role in controlling the virus (Lu et al., 2023). MPXV MOPICE has been shown to block complement pathway activation in studies involving viable variola virus (VARV) and VACV MOPICE. Increased viral multiplication in vivo and decreased adaptive immune responses in MPXV-infected rhesus macaques lacking MOPICE expression are examples of how MOPICE affects antiviral immune responses (Liszewski et al., 2006). Since Clade II lacks the D14L gene, viruses, and virus-infected cells are believed to be vulnerable to host complement attack. Nevertheless, Clade II’s expression of MOPICE did not make it more virulent, suggesting that MOPICE is not the only factor influencing the variations in viral virulence between the two clades.

How MPXV might affect the adaptive immune system is unclear. Through suppression of T cell receptor-mediated T cell activation, MPXV impedes the antiviral CD8+ and CD4+ T cell responses that make up the adaptive immune response (Li et al., 2023). VACV A35 impedes MHC class II-restricted antigen presentation which prevents T cell immunity (Rehm et al., 2010). Furthermore, infection tests using MPXV cells lacking the A35R gene revealed that A35 suppresses the production of chemokines and cytokines (Alakunle et al., 2024). The counterpart of MPXV A35 and A37 may inhibit the presentation of viral antigens to immune cells and aid in the virus’s ability to elude the body’s defenses (Zandi et al., 2023). Nevertheless, MPXV does not seem to affect MHC expression or the transit of MHC molecules within cells.

Pathology

The characteristic feature of MPXV infection is swelling of the maxillary, cervical, or inguinal lymph nodes (lymphadenopathy) (Malik et al., 2023). An investigation from Portugal during a recent outbreak revealed that inguinal lymphadenopathy was more prevalent than cervical and axillary lymphadenopathy (Nisar et al., 2023). Following the onset of a fever, the rash develops and first appears on the face, tongue, and oral cavity (enanthem) before moving throughout the body (Altindis et al., 2022). When an illness reaches a more advanced stage, oral cavity lesions can make it difficult to eat and drink. Nonetheless, there have been some documented odd clinical observations in recent epidemics. This includes anal ulcers and vaginal lesions that eventually spread to other regions of the body in homosexual patients. It also seems that skin lesions may have a more restricted spread than those seen in earlier outbreaks (Wong et al., 2022).

The number of lesions can be used to classify the severity of the disease, as more lesions are associated with a higher risk of serious consequences (Hasan and Saeed, 2022). Severe consequences can cause encephalitis, septicemia, respiratory and intestinal issues, and eye infections that result in irreversible vision loss in patients (Rabaan et al., 2023). Additionally, skin lesions raise the risk of bacterial skin infections, particularly in individuals who have not had the smallpox vaccination.

Prior to scabbling over, lesions often go through four stages: macular, papular, vesicular, and pustular (Ortiz-Martínez et al., 2022). Patients who have crusted over their lesions are typically deemed non-infectious. Even after shedding, scabs have been found to contain significant levels of MPXV DNA which may suggest the presence of infectious viral material (Lum et al., 2022). Notably, scabs from smallpox victims have been found to contain live VARV.

MPXV can spread vertically from mother to fetus during pregnancy (Najimudeen et al., 2022). In a study involving four pregnant women infected with MPXV in Congo, only one gave birth to a healthy baby (Mbala et al., 2017). In the first trimester, two women miscarried, and one lady gave birth to a stillborn child; skin lesions were noticeable on the bodies of stillborn babies. In a different investigation, lesions on the surface of the mother’s placenta and fetal mortality were experienced by four out of five mothers in Congo who were infected with MPXV (Schwartz and Pittman, 2023). The MPXV group that these patients were infected with was not disclosed in the study; however, considering the study’s setting, it was most likely the Central African MPXV group.

A study conducted in Zaire reported a higher incidence of fatal disease in young children infected with MPXV, with a mortality rate of 14.9% in children aged between 0 and 4 years compared to a rate of 0% in individuals aged 10 years or older (Lum et al., 2022). Their distinct immunological responses could be the cause of this discrepancy. There is currently insufficient data on the severity of illness in children infected with the West African lineage. However, the serious effects of monkeypox on expectant mothers and young children underscore the significance of ongoing public health initiatives aimed at curbing the proliferation of MPXV and reducing the likelihood of unfavorable outcomes.

Clinical symptoms

Monkeypox symptoms can vary. While some people may only experience mild symptoms, others may have more serious ones that call for medical attention. The incubation period for MPXV infection is 5–21 days (Ahmed et al., 2023b). The most typical signs and symptoms include myalgia, fever, headache, back pain, malaise, and swollen lymph nodes (Luo and Han, 2022). There may be a rash that lasts for 2–3 weeks in addition to or after these symptoms (Nyame et al., 2023).

Monkeypox symptoms include an incubation period of 5–21 days, divided into two parts: the prodromal and the eruption phases (Huang et al., 2022). Prodromal symptoms, which include fever, headache, weakness, back and muscle discomfort, and swollen lymph nodes with lumps in the groin, armpits, and neck can continue for up to 5 days (Wang and Lun, 2023). During the eruption phase, which starts 3 days after the fever, a reddish rash first appears on the face and then spreads to the hands, feet, eyes, mouth, throat, and genital areas, including the penis, vulva, and anus (Altindis et al., 2022). Usually, the reddish rash or patches begin as spots and progress into vesicles, or blisters, which are skin blisters packed with liquid (Luo and Han, 2022). The rash will dry up and turn into a crust (scab) on the skin after a few days.

There can be one to hundreds of rash lesions. Macular lesions typically show up first, then progress to papular, vesicular, pustular, and finally desquamation (Long et al., 2022). These lesions are often firm and frequently form an umbilical cord at the lesion’s tip. The healing process normally causes these lesions to become itchy and uncomfortable (Sobral-Costas et al., 2023). Until all lesions have healed, the patient will continue to spread the disease. In addition, anal symptoms may also coexist with monkeypox. Symptoms of monkeypox include purulent or bloody discharge, anal discomfort, or bleeding from the rectum (Messina et al., 2022). Those who are affected may experience respiratory symptoms such as coughing, blocked noses, and sore throats (Meng, 2022). Typically, the skin rash progresses from patches to scabs in about 10 days. The body’s scabs take around 3 weeks to completely come off on their own (Hussain et al., 2022). The absence of new resilience indicates that the condition is no longer contagious.

In general, groups that are more prone to bacterial or viral infections or typically exhibit more severe symptoms include children, particularly those under the age of eight; individuals with impaired immune systems; those suffering from cancer; those undergoing drug therapy; and pregnant women (Letafati and Sakhavarz, 2023). When exhibiting symptoms, it is advised to take more breaks and make sure that one is getting enough food and fluids. In addition, patients must self-quarantine by remaining at home and minimizing social interactions with others in the neighborhood. It is advised that patients with severe symptoms check into a hospital to receive comprehensive care (Polk et al., 2023).

Diagnosis

As stated in the ongoing outbreak in 2022, it is critical to have a high degree of suspicion regarding monkeypox infection and to be vigilant about the occasionally unusual symptoms of infection. The doctor should inquire about travel and sexual history, as well as close contact with persons who have experienced a similar rash or who have suspected or confirmed monkeypox infection, if there is a clinical suspicion of the illness (Titanji et al., 2022). Living in the same home, sharing a bathroom, sleeping in the same room, eating or drinking from the same container, and other similar behaviors are examples of close contact behaviors (Nolen et al., 2015). More significantly, this diagnosis is not ruled out in the absence of a travel history, a specific intimate encounter with a known rash, or a suspected or confirmed case of monkeypox (Hong et al., 2023). It is also important to have a comprehensive skin inspection.

The accurate diagnosis of Monkeypox disease is essential for its effective treatment and control. The best course of action for diagnosing individuals who may be suffering from active monkeypox is to remove a sample of skin from the lesion (Fig. 3) and perform PCR molecular testing (Altindis et al., 2022).

Ideally, more than 1 specimen should be collected from 2 independent lesions on various areas of the body, and the lesions should be roofless to adequately extract virus-carrying fluids. While some facilities are capable of performing direct PCR testing for MPXV specifically, others are only able to perform general OPXV testing, necessitating MPXV confirmation testing at a reference laboratory (Osborn et al., 2022). Nonetheless, in light of an ongoing outbreak, a positive OPXV test could be interpreted as a diagnosis of monkeypox infection before the availability of findings from additional testing (Vierbaum et al., 2023). Before the collection of specimens, testing strategies should preferably be coordinated with public health authorities.

Viral strains for additional characterization are obtained by cell culture, which is only available in approved biosafety level 3 reference facilities (Watanabe et al., 2023). Serologic testing may be helpful for diagnosing late clinical symptoms, including encephalitis, as well as for epidemiological studies and retrospective diagnosis of previous infections (Nyame et al., 2023). It is not concerning for unvaccinated individuals that MPXV serology may react negatively to prior smallpox vaccinations (Li et al., 2024b).

Fig. 3. Collection of skin sample for monkeypox diagnosis [Source: World Health Organization (2024)].

Some researchers already developed valuable and insightful imaging techniques which involve the use of cutting-edge computational algorithms such as specifically Visual Geometry Group (VGG)- 16, Residual Network (ResNet)- 50, ResNet101, and vision transformer (ViT) for the prediction and diagnosis of monkeypox with high accuracy amid the persisting global outbreak (Ahsan et al., 2024).

Differential diagnosis

In cases of monkeypox, chickenpox is the most frequently used differential diagnosis (Tumewu et al., 2020). In contrast to chickenpox, which has a short prodromal period, centripetal rash distribution, no lymphadenopathy, and an acceleration of rash spread, monkeypox is characterized by a long prodromal period, centrifugal rash spread, and slower lesions spread (Sharma et al., 2022). The following conditions should be distinguished from monkeypox: measles, drug eruption, molluscum contagiosum, hand-foot-and-mouth disease, and infected scabies (Long et al., 2022).

Transmission

According to a recent study, there are three possible ways that monkeypox might spread: from person to person, from animals to humans, and through direct contact with an infected creature (Hakim and Widyaningsih, 2023). It is recognized that people can contract the MPXV from animals. Most known virus-carrying animals are rodents, including mice, squirrels, and dormice, as well as different primates (Upadhayay et al., 2022). However, there is proof that MPXV can spread from person to person outside of Africa. Additionally, eating contaminated bushmeat and breathing in droplets from infected people are two other possible ways the virus can spread (Chaix et al., 2022). Researchers have discovered that men who have intercourse with other men are more likely to have this disease during its outbreak (Martínez et al., 2022). Most monkeypox cases have been identified in men who have had sex with other men. It is possible for the virus to spread through contact with infected individuals. Furthermore, a novel discovery has been made by semen analysis in numerous cases, which has shown the existence of MPXV DNA (Li et al., 2022b). This virus can spread from person to person by direct contact with an infected individual’s bodily fluids, respiratory contact (air), or from a pregnant woman to her fetus (Yan et al., 2023). Given that pathogenic MPXV can be identified from samples of semen, there are indications that sexual contact may be the means of transmission (Barboza et al., 2023). MPXV may accumulate in the vaginal region if it is present in seminal fluid for an extended period of time (Luo and Han, 2022). It is still unclear if the virus can spread through vaginal secretions. The virus can spread through items or indirect contact with lesioned materials such as contaminated bedding, even with proper personal protective equipment. Inhalation is the most common way for the virus to spread (Lepelletier et al., 2022). A risk factor for transmission is sleeping in the same bed or room as an infected individual or sharing equipment (Pinto et al., 2023). There is a correlation between factors related to viral entrance into the oral mucosa and a higher probability of transmission (Karagoz et al., 2023). Whether those who do not exhibit monkeypox symptoms can still spread the virus is still unknown. Though it is generally agreed upon that this strain of West African ancestry is not unique, further research is currently being done to better understand how it spread (Srivastava et al., 2023). Unlike COVID-19, MPXV does not currently disperse through the air. Monkeypox is not communicable until an infected person exhibits symptoms, in contrast to COVID-19 (Farasani, 2022). As a result, it is considerably simpler to keep sick people apart and prevent the disease from spreading.

Risk factor

Even if the primary risk variables that are connected with an epidemic vary depending on the outbreak, it is crucial to gather specific individual characteristics to quantify and predict epidemic trends. Monkeypox cases that spread to humans typically involve females, people who do not obtain smallpox vaccinations, people who dwell in the same house, and those who treat main cases (Koenig et al., 2022). Notably, investigations of outbreaks in endemic nations reveal that children bear a heavy burden of MPXV infection; however, this information is based on monkeypox-related clade 1 in the DRC and does not represent other enzootic regions (Luna et al., 2023). The majority of those engaged in the clade 2-associated monkeypox incidence in the Nigerian region were between the ages of 21 and 40, with an 11-year-old teenager serving as the index case (Riopelle et al., 2022). The function of social and behavioral determinants in facilitating the transmission of MPXV infection from person to person is defined by these linked risk factors. However, detailed descriptions of the risk factors linked to the initial introduction of monkeypox can be found in comprehensive reviews and meta-analyses.

Nosocomial MPXV infection, also known as healthcare-associated infection (HAI), is an infection obtained during the course of receiving healthcare services that is not present in the hospital at the time of admission in both enzootic and non-enzootic areas. It is one of the major associated risk factors for patients and healthcare workers (Ullah et al., 2023). Moreover, smallpox is mostly caused by nosocomial infections, with health centers experiencing the highest rates of transmission. Similarly, the majority of cases of monkeypox that are spread in hospitals are severe and chronic (Peng et al., 2023). Aerosol-generating measures, hospital cleanliness practices, and disease-susceptible individuals are some of these constant multifactorial consequences. In a public health clinic located in Impfondo, Republic of the Congo, six generations of MPXV spread were examined (Zahmatyar et al., 2023). The investigation highlighted the possibility of MPXV spreading if medical institutions do not promptly treat it. A healthcare worker who once acquired MPXV after gathering blankets and garments from individuals suffering from monkeypox in England (Carvalho et al., 2022).

Direct contact with the blood, bodily fluids, or mucosal or skin lesions of infected animals can result in zoonotic transmission, or the spread of infection from animals to people (Kaswa et al., 2022). Monkeypox has been documented in Africa in a range of hosts, including numerous species of monkeys, dormice, Gambian mice, tree squirrels, rope squirrels, and other animals (Ullah et al., 2023). Although the source of monkeypox is yet unknown, rodents are the anticipated but unidentified main animal. One possible risk factor is eating raw meat and other items that come from diseased animals (Ahmed et al., 2023b). People who live in or close to forests may have unintentionally come into contact with diseased animals at low levels.

Human-to-human transmission can happen through cutaneous abrasions from infected people, close contact with respiratory fluids, or newly infected individuals (Khamees et al., 2023). Public health workers, relatives, and other close contacts of active cases are more at risk since the respiratory particle spread of MPXV usually necessitates extended and close encounters (Beeson et al., 2023). Since the smallpox vaccination program is no longer in place, the sequence of predicted spread in the population has increased from six to nine repeat human-to-human contaminations (Lai et al., 2022). This could mean that human protection has decreased.

There have been rare reports of MPXV being transferred from humans to animals, and it is thought that animal infection may not have been the source of the outbreak. To prevent the transmission of the virus, European health organizations strongly advise that rodents belonging to individuals suffering from monkeypox, such as guinea pigs and hamsters, be confined, closely watched, or even put to death (Ullah et al., 2023). Nevertheless, two cases of human-to-dog transmission that were documented in France and Brazil in August 2022 represent the most recent identification (Zahmatyar et al., 2023). Two people with monkeypox in Paris had a 4-year-old male Italian Greyhound as a pet dog, and the dog was also diagnosed with the disease. Dogs exhibited homology in DNA sequencing when the virus was discovered in individual cases. This dog displayed signs like an abdominal abscess and tested positive for MPXV. Researchers came to the conclusion that MPXV was in fact transmitted between humans and dogs based on the sequencing data, and symptoms in the two patients, and the dog (Ferdous et al., 2022).

Disease examinations show that young adults and adults with weakened immune systems, such as those infected with HIV should be the primary focus of attention (O’Neill et al., 2023). The potential that the virus may have undergone genetic mutation and that human behavior may have evolved or accumulated is suggested by the current worldwide incidence of monkeypox in humans. The resumption of intercontinental migration, sexual activity, weakened immunity to smallpox and weakened COVID-19 preventive measures could all contribute to this mutation (Sharma et al., 2023). An additional known factor in the current topographic distribution of MPXV spread is sexual interactions, particularly among men who have sex with other men (Raccagni et al., 2022).

Treatment

Certain treatments created for smallpox can also be used to treat monkeypox; however, the effectiveness of these treatments is primarily dependent on preclinical research, with minimal human clinical data to support their use. The antiviral medication tecovirimat targets the membrane protein VP37 MPXV to stop the virus from forming enveloped virions that can leave the cell, preventing the virus from spreading (Russo et al., 2021). It has no effect on the intracellular mature virus. In nonhuman primate (NHP) models, tecovirimat is useful in lessening the severity of monkeypox; however, its efficacy is diminished if treatment is administered more than 5 days following challenge (de la Calle-Prieto et al., 2023). This is a warning that tecovirimat should not be taken based only on the appearance of symptoms, as they may not show up until much later in the infection. As opposed to six individuals who were not treated, one patient in a small study who had monkeypox showed a reduced length of illness and virus shedding after receiving tecovirimat (Yan et al., 2023).

Bicidofovir, another monkeypox treatment, is authorized by the Food and Drug Administration (FDA) but not by the European Medicines Agency (EMA). Brincidofovir prevents DNA synthesis mediated by the OPXV (Bruno and Buccoliero, 2023). This medication has shown effectiveness in treating monkeypox in mouse and dog models. Three individuals in the same small trial mentioned above received brincidofovir treatment; nevertheless, all three had to stop their medication because of toxicity (increased liver enzymes) (Kumar et al., 2023). The active version of brincidofovir, called cidofovir28, is nephrotoxic but likewise exhibits antipoxviral action in vitro and in animal tests (Ganapthy et al., 2023).

In addition to having cross-neutralizing activity against MPXV in rhesus macaques, vaccine immune globulin (VIG) exhibits encouraging efficacy in preventing smallpox in those who have been exposed (Gilchuk et al., 2016). Nevertheless, no mAb or antibody cocktail, including VIG has been clinically investigated for monkeypox immunity.

Vaccination

The smallpox vaccine has undergone three stages of development. Originally, the smallpox vaccine was administered by first reproducing it on the skin of the calf and then extracting it from its lymph (Saadh et al., 2023). However, mass population vaccination (MPV) programs are currently prohibited from using this vaccine. Second-generation smallpox vaccinations, on the other hand, were created using exacting and sophisticated methods and were grown in tissue cell cultures, which decreased the risk of infection (Chakraborty et al., 2022). Furthermore, it has been demonstrated that each of these generations may have a sizable risk of unfavorable results since they include replicating VAVCs. The second-generation smallpox vaccine and the third-generation vaccine employ the same methodology. However, because the VAVC in this vaccine is attenuated and has a lower capacity for replication, it offers greater safety (Sah et al., 2023). The second-generation smallpox vaccine, ACAM2000, has been licensed by the FDA for use as a preventative strategy following exposure in emergency situations or during smallpox outbreaks (Chopra et al., 2022). The MVA-BN vaccine, also known as JYNNEOSTM, was approved following animal research conducted in the United States and Canada. High efficacy and safety have been shown in clinical trials, making it a viable choice for avoiding MPXV infections in a variety of groups (Priyamvada et al., 2022). Japan and the FDA have authorized LC16. In the first two weeks, vaccination can help avoid serious illness. According to research, administering the smallpox vaccine quickly is more successful at preventing MPXV infection (Christodoulidou and Mabbott, 2023). Nonetheless, a potent vaccine for MPXV is available at this time.

There are three OPXV vaccines on the market: LC16, JYNNEOS, and ACAM2000 (Abdelaal et al., 2022). The FDA authorized ACAM2000 in 2015 for use in the US to combat smallpox and monkeypox. In the nation, from 2015 to 2019, this was the only monkeypox vaccine accessible (Sah et al., 2022b). ACAM2000 is a second-generation, plaque-purified, attenuated VAVC vaccine that is replication-competent. Using a two-pronged needle scarification procedure and many skin surface inoculations, this vaccine is applied via the skin. Within 28 days of injection, this vaccination offers the best protection. For people exposed to highly virulent strains of the orthopox virus, booster shots are advised every 3 years; for people exposed to less virulent strains, such as VAVC or cowpox virus, booster doses are advised every 10 years (Hung et al., 2022). The live attenuated, non-replicable Ankara vaccine is known as the MVA-BN vaccine. The vaccination lasts for 2 weeks after the second dosage and requires two doses spaced 28 days apart. After the initial dosage, clinical investigations have shown a significant antibody response. Two weeks following immunization, an immune response can be seen. A booster dose is necessary every 2 years for people infected with the extremely virulent orthopox virus and every 10 years for those exposed to the less virulent orthopox virus (Reina and Iglesias, 2023). The third-generation LC16 vaccine was created and licensed in Japan, and then approved for use against smallpox in the United States; however, it was not approved for use against monkeypox. Cell culture is used to create this live attenuated vaccine with limited multiplication. The Lister strain serves as the source of the LC16 vaccine, which lacks the immunogenic membrane protein B5R. This vaccine can be given as part of a multidose schedule to people of any age, including infants and children, and is delivered through the skin using a two-pronged needle (Kenner et al., 2006). Evaluate variables including reactogenicity, safety, and vaccine-related side effects to determine which vaccinations are most effective, particularly for vulnerable and high-risk populations. Numerous OPXV vaccines have been created and are currently being researched.

Control

Prevention for individuals, households, and communities

During a monkeypox outbreak, hand hygiene is advised. The individual should refrain from sharing intimate objects that might contain virus particles (Hernaez et al., 2023). Wearing a mask that fits properly, wearing disposable gloves, and keeping a minimum of one meter between themselves and suspected or confirmed patients are all advised for nurses (Dubey et al., 2023). Patients who have the infection should stay alone and stay away from people and domesticated animals until all sores have crusted over, scabs have fallen off, and a new layer of skin has grown underneath them (Gomez-Lucia, 2022). However, even after all lesions have healed, MPXV might still be present in bodily fluids. Six weeks may pass after the last interaction with an infected person or animal (Nolen et al., 2016). The WHO advises using condoms for receptive or insertive sex for a period of 12 weeks following recovery for individuals who are sexually active.

A monkeypox sufferer needs to be kept apart from other uninfected family members in a well-ventilated room at home (Lepelletier et al., 2022). The designated individual must be in excellent health, not be at high risk of getting serious monkeypox sickness, and have received the smallpox vaccination if the patient needs help with self-care (Saadh et al., 2023). It is important to provide caregivers with information on how diseases spread and how to prevent them.

Poxviruses can thrive on household objects, particularly in conditions that are dry, cold, and dark (Rajsri and Rao, 2022). A live virus was discovered suspended in a patient’s home for a period of 15 days. It is advised that every space that sick patients occupy should be disinfected (Eggers et al., 2022). Compared to non-porous surfaces, porous surfaces may hold live viruses for a longer period of time (Morgan et al., 2022) and the washing of patient’s clothing and bedding in soapy water, preferably heated to at least 60°C is important. When cleaning furniture in the home, shaking, dusting, sweeping, or vacuuming should be avoided to curtail the aerosolization of virus particles. Additionally, patient’s waste should be put in a tight-fitting bag; chlorine addition may also lessen contamination (Harapan et al., 2022).

There is no proof of how to deliver an infected pregnancy to stop the infection from spreading from mother to child; however, procedures for a cesarean section have to follow standard protocols. Nonetheless, if any genital lesions are found, cesarean delivery is advised. Infants born to mothers who are sick should have their viral DNA analyzed and their symptoms monitored (Gaeta et al., 2022). As of right now, there is no proof that the virus can spread to infants through breastfeeding or that virus antibodies can be found in breast milk. Taking into mind the mother’s status, the degree of monkeypox sickness, and risk and benefit calculations, this practice should be evaluated case-by-case (Yan et al., 2023).

Prevention and control in health care settings

Contact and droplet precautions apply to confirmed cases. Health professionals are required to wear personal protection equipment (PPE) in addition to washing their hands (Manirambona et al., 2023). Since there is currently insufficient data to support the theory that monkeypox can spread by air, respiratory support is advised. If aerosol-generating processes are carried out, it is advised to take precautions against airborne transmission (Wang et al., 2022).

Healthcare personnel exposed to patients with monkeypox who lack proper protection should actively watch for symptoms and take their body temperature at least twice a day for 21 days following exposure, as opposed to placing them in isolation (Lulli et al., 2022).

Patients should be segregated into a well-ventilated isolation space and wear a medical mask that fits properly and covers the lesion (Harapan et al., 2022). A minimum of one meter must separate patients in confirmed cases. Even after all scabs have fallen off, individuals with severe cases or compromised immune systems may continue to release viruses in their respiratory secretions (Khattak et al., 2023). A case-by-case analysis might be required.

There is insufficient information on monkeypox among medical professionals and students in health schools, according to both past and present data (Swed et al., 2023). Furthermore, in a variety of contexts, there is a poor degree of trust in the diagnosis and treatment of monkeypox. This demonstrates the critical need for intervention strategies involving education and training to support the prevention and management of continuing outbreaks.

The most recent study provides a detailed account of how suitable public health measures were implemented to stop the spread of MPXV. In particular, specific actions in community and healthcare settings include: rigorous monitoring to identify and isolate infections as soon as possible; given the present evidence of low confidence in the abilities of physicians and nurses to detect and treat disease, training for healthcare personnel should enable accurate and quick clinical diagnosis. Considering the wide range of differential diagnoses for patients presenting with nonspecific symptoms and acute rashes of unknown cause, the availability of precise laboratory diagnostic techniques cannot be disregarded, in addition to adhering to recommended infection control practices, such as wearing personal protective equipment and following disinfection protocols (Koenig et al., 2022).

---

Conclusion

After fewer than 50 years, the monkey pox virus reached epidemic proportions once more in 2022. The host reservoir of MPXV, in particular, remains unknown, and research is still ongoing to determine how the virus, host, and environment interact to control the virus’s maintenance in the wild, animal-to-animal transmission, zoonotic transmission, and reverse spread. In order to create effective treatments and vaccines against MPXV infection, current and future research should prioritize understanding the molecular basis of MPXV infection. Additionally, studies of functional mutations will shed light on the dynamics of MPXV transmission between hosts. Particularly in nations with limited resources, laboratories need to be outfitted with genome-based monitoring tools and capacities in order to enhance MPXV tracking and its effect on human, animal, and ecological health. Control techniques are therefore desperately needed for the treatment and prevention of both present and future monkeypox outbreaks.

---

Acknowledgments

The authors thank Universitas Airlangga and Badan Riset dan Inovasi Nasional (BRIN).

Funding

The author thank Universitas Airlangga for the funding support with grant number 397/UN3.14/PT/2020.

Author’s contributions

SA, ARK, MKJK, and IBM drafted the manuscript. NH, MA, IM, and RR revised and edited the manuscript. ANN, KHPR, SW, and KAF took part in preparing and critical checking of the manuscript. MTEP, MGAY, AHF, and MA edited the references. All authors read and approved the final version of the manuscript.

Conflict of interest

The authors declare that there is no conflict of interest.

Data availability

All references are open access, so data can be obtained from the online web.

---

References

Abdelaal, A., Reda, A., Lashin, B.I., Katamesh, B.E., Brakat, A.M., Al-Manaseer, B.M., Kaur, S., Asija, A., Patel, N.K., Basnyat, S., Rabaan, A.A., Alhumaid, S., Albayat, H., Aljeldah, M., Shammari, B.R.A., Al-Najjar, A.H., Al-Jassem, A.K., AlShurbaji, S.T., Alshahrani, F.S., Alynbiawi, A., Alfaraj, Z.H., Alfaraj, D.H., Aldawood, A.H., Sedhai, Y.R., Mumbo, V., Rodriguez-Morales, A.J. and Sah, R. 2022. Preventing the next pandemic: is live vaccine efficacious against monkeypox, or is there a need for killed virus and mRNA vaccines? Vaccines (Basel) 10(9), 1419.

Agrati, C., Cossarizza, A., Mazzotta, V., Grassi, G., Casetti, R., De Biasi, S., Pinnetti, C., Gili, S., Mondi, A., Cristofanelli, F., Lo Tartaro, D., Notari, S., Maffongelli, G., Gagliardini, R., Gibellini, L., Aguglia, C., Lanini, S., D’Abramo, A., Matusali, G., Fontana, C., Nicastri, E., Maggi, F., Girardi, E., Vaia, F. and Antinori, A. 2023. Immunological signature in human cases of monkeypox infection in 2022 outbreak: an observational study. Lancet Infect. Dis. 23(3), 320–330.

Ahmed, S.K., El-Kader, R.G.A., Abdulqadir, S.O., Abdullah, A.J., El-Shall, N.A., Chandran, D., Dey, A., Emran, T.B. and Dhama, K. 2023b. Monkeypox clinical symptoms, pathology, and advances in management and treatment options: an update. Int. J. Surg. 109(9), 2837–2840.

Ahmed, S.K., Mohamed, M.G., Dabou, E.A., Abuijlan, I., Chandran, D., El-Shall, N.A., Chopra, H. and Dhama, K. 2023a. Monkeypox (mpox) in immunosuppressed patients. F1000Res 12(1), 127.

Ahsan, M.M., Alam, T.E., Haque, M.A., Ali, M.S., Rifat, R.H., Nafi, A.A.N., Hossain, M.M., Islam, M.K. 2024. Enhancing monkeypox diagnosis and explanation through modified transfer learning, vision transformers, and federated learning. Inf. Med. Unlocked 45, 101449.

Al-Musa, A., Chou, J. and LaBere, B. 2022. The resurgence of a neglected orthopoxvirus: immunologic and clinical aspects of monkeypox virus infections over the past six decades. Clin. Immunol. 243(1), 109108.

Alakunle, E., Kolawole, D., Diaz-Cánova, D., Alele, F., Adegboye, O., Moens, U. and Okeke, M.I. 2024. A comprehensive review of monkeypox virus and mpox characteristics. Front. Cell. Infect. Microbiol. 14(1), 1360586.

Alejo, A., Sánchez, C., Amu, S., Fallon, P.G. and Alcamí, A. 2019. Addition of a viral immunomodulatory domain to etanercept generates a bifunctional chemokine and TNF inhibitor. J. Clin. Med. 9(1), 25.

Aljabali, A.A., Obeid, M.A., Nusair, M.B., Hmedat, A. and Tambuwala, M.M. 2022. Monkeypox virus: an emerging epidemic. Microb. Pathog. 173(Pt A), 105794.

Altindis, M., Puca, E. and Shapo, L. 2022. Diagnosis of monkeypox virus - an overview. Travel. Med. Infect. Dis. 50(1), 102459.

Arndt, W.D., Cotsmire, S., Trainor, K., Harrington, H., Hauns, K., Kibler, K.V., Huynh, T.P. and Jacobs, B.L. 2015. Evasion of the innate immune type I interferon system by monkeypox virus. J. Virol. 89(20), 10489–10499.

Arndt, W.D., White, S.D., Johnson, B.P., Huynh, T., Liao, J., Harrington, H., Cotsmire, S., Kibler, K.V., Langland, J. and Jacobs, B.L. 2016. Monkeypox virus induces the synthesis of less dsRNA than vaccinia virus, and is more resistant to the anti-poxvirus drug, IBT, than vaccinia virus. Virology 497(1), 125–135.

Bahar, M.W., Kenyon, J.C., Putz, M.M., Abrescia, N.G., Pease, J.E., Wise, E.L., Stuart, D.I., Smith, G.L. and Grimes, J.M. 2008. Structure and function of A41, a vaccinia virus chemokine binding protein. PLoS Pathog. 4(1), e5.

Banuet-Martinez, M., Yang, Y., Jafari, B., Kaur, A., Butt, Z.A., Chen, H.H., Yanushkevich, S., Moyles, I.R., Heffernan, J.M. and Korosec, C.S. 2023. Monkeypox: a review of epidemiological modelling studies and how modelling has led to mechanistic insight. Epidemiol. Infect. 151(1), e121.

Barboza, J.J., León-Figueroa, D.A., Saldaña-Cumpa, H.M., Valladares-Garrido, M.J., Moreno-Ramos, E., Sah, R., Bonilla-Aldana, D.K. and Rodriguez-Morales, A.J. 2023. Virus identification for monkeypox in human seminal fluid samples: a systematic review. Trop. Med. Infect. Dis. 8(3), 173.

Beeson, A., Styczynski, A., Hutson, C.L., Whitehill, F., Angelo, K.M., Minhaj, F.S., Morgan, C., Ciampaglio, K., Reynolds, M.G., McCollum, A.M. and Guagliardo, S.A.J. 2023. Mpox respiratory transmission: the state of the evidence. Lancet Microbe 4(4), e277–e283.

Bou-Nader, C., Gordon, J.M., Henderson, F.E. and Zhang, J. 2019. The search for a PKR code-differential regulation of protein kinase R activity by diverse RNA and protein regulators. RNA 25(5), 539–556.

Brandstadter, J.D. and Yang, Y. 2011. Natural killer cell responses to viral infection. J. Innate Immun. 3(3), 274–279.

Bruno, G. and Buccoliero, G.B. 2023. Antivirals against monkeypox (Mpox) in humans: an updated narrative review. Life 13(10), 1969.

Bunge, E.M., Hoet, B., Chen, L., Lienert, F., Weidenthaler, H., Baer, L.R. and Steffen R. 2022. The changing epidemiology of human monkeypox-A potential threat? A systematic review. PLoS Negl. Trop. Dis. 16(2), e0010141.

Carvalho, L.B., Casadio, L.V.B., Polly, M., Nastri, A.C., Turdo, A.C., de Araujo Eliodoro, R.H., Sabino, E.C., Levin, A.S., de Proença, A.C.T. and Higashino, H.R. 2022. Monkeypox virus transmission to healthcare worker through needlestick injury, Brazil. Emerg. Infect. Dis. 28(11), 2334–2336.

Chadha, J., Khullar, L., Gulati, P., Chhibber, S. and Harjai, K. 2022. Insights into the monkeypox virus: making of another pandemic within the pandemic? Environ. Microbiol. 24(10), 4547–4560.

Chaix, E., Boni, M., Guillier, L., Bertagnoli, S., Mailles, A., Collignon, C., Kooh, P., Ferraris, O., Martin-Latil, S., Manuguerra, J.C. and Haddad, N. 2022. Risk of monkeypox virus (MPXV) transmission through the handling and consumption of food. Microb. Risk Anal. 22(1), 100237.

Chakraborty, C., Bhattacharya, M., Sharma, A.R. and Dhama, K. 2022. Monkeypox virus vaccine evolution and global preparedness for vaccination. Int. Immunopharmacol. 113(Pt A), 109346.

Chen, N., Li, G., Liszewski, M.K., Atkinson, J.P., Jahrling, P.B., Feng, Z., Schriewer, J., Buck, C., Wang, C., Lefkowitz, E.J., Esposito, J.J., Harms, T., Damon, I.K., Roper, R.L., Upton, C. and Buller, R.M. 2005. Virulence differences between monkeypox virus isolates from West Africa and the Congo basin. Virology 340(1), 46–63.

Chopra, H., Dhawan, M., Bibi, S., Baig, A.A., Kushwah, A.S., Kaur, M. and Emran, T.B. 2022. FDA approved vaccines for monkeypox: current eminence. Int. J. Surg. 105(1), 106896.

Chowdhury, P.P.D., Haque, M.A., Ahamed, B., Tanbir, M. and Islam, M.R. 2022. A brief report on monkeypox outbreak 2022: historical perspective and disease pathogenesis. Clin. Pathol. 15(1), 2632010X221131660.

Christodoulidou, M.M. and Mabbott, N.A. 2023. Efficacy of smallpox vaccines against Mpox infections in humans. Immunother. Adv. 3(1), ltad020.

Cohn, H., Bloom, N., Cai, G., Clark, J., Tarke, A., Bermúdez-González, M.C., Altman, D., Lugo, L.A., Lobo, F.P., Marquez, S., Chen, J.Q., Ren, W., Qin, L., Crotty, S., Krammer, F., Grifoni, A., Sette, A., Simon, V. and Coelho, C.H. 2023. Mpox vaccine and infection-driven human immune signatures. Lancet Infect. Dis. 23(11), 1302–1312.

de la Calle-Prieto, F., Muñoz, M.E., Ramírez, G., Díaz-Menéndez, M., Velasco, M., Galparsoro, H.A., Lletí, M.S., Forte, T.M., Blanco, J.L., Mora-Rillo, M., Arsuaga, M., de Miguel Buckley, R., Arribas, J.R., Membrillo, F.J. and Working Group of the UAAN – Grupo de Estudio de Patología Importada (GEPI) and the Working Group of the Monkeypox at the SEIMC. 2023. Treatment and prevention of monkeypox. Enferm. Infecc. Microbiol. Clin. (Engl Ed) 41(10), 629–634.

Di Giulio, D.B. and Eckburg, P.B. 2004. Human monkeypox: an emerging zoonosis. Lancet Infect. Dis. 4(1), 15–25.

Domán, M., Fehér, E., Varga-Kugler, R., Jakab, F. and Bányai, K. 2022. Animal models used in monkeypox research. Microorganisms 10(11), 2192.

Dou, Y.M., Yuan, H. and Tian, H.W. 2023. Monkeypox virus: past and present. World J Pediatr. 19(3), 224–230.

Dubey, T., Chakole, S., Agrawal, S., Gupta, A., Munjewar, P.K., Sharma, R. and Yelne, S. 2023. Enhancing nursing care in monkeypox (Mpox) patients: differential diagnoses, prevention measures, and therapeutic interventions. Cureus 15(9), e44687.

Earl, P.L., Americo, J.L. and Moss, B. 2020. Natural killer cells expanded in vivo or ex vivo with IL-15 overcomes the inherent susceptibility of CAST mice to lethal infection with orthopoxviruses. PLoS Pathog. 16(4), e1008505.

Eggers, M., Exner, M., Gebel, J., Ilschner, C., Rabenau, H.F. and Schwebke, I. 2022. Hygiene and disinfection measures for monkeypox virus infections. GMS Hyg. Infect. Control 17(1), Doc18.

Farasani, A. 2022. Monkeypox virus: future role in human population. J. Infect. Public Health 15(11), 1270–1275.

Ferdous, J., Barek, M.A., Hossen, M.S., Bhowmik, K.K. and Islam, M.S. 2022. A review on monkeypox virus outbreak: new challenge for world. Health Sci. Rep. 6(1), e1007.

Gaeta, F., De Caro, F., Franci, G., Pagliano, P., Vajro, P. and Mandato, C. 2022. Monkeypox infection 2022: an updated narrative review focusing on the neonatal and pediatric population. Children (Basel) 9(12), 1832.

Ganapthy, D., Sekaran, S. and Sekar, S.K.R. 2023. Monkeypox treatment options: current status of antiviral drugs - a correspondence. Int. J. Surg. 109(3), 562–563.

Ghate, S.D., Suravajhala, P., Patil, P., Vangala, R.K., Shetty, P. and Rao, R.S.P. 2023. Molecular detection of monkeypox and related viruses: challenges and opportunities. Virus Genes 59(3), 343–350.

Ghosh, N., Chacko, L., Vallamkondu, J., Banerjee, T., Sarkar, C., Singh, B., Kalra, R.S., Bhatti, J.S., Kandimalla, R. and Dewanjee, S. 2023. Clinical strategies and therapeutics for human monkeypox virus: a revised perspective on recent outbreaks. Viruses 15(7), 1533.

Gilchuk, I., Gilchuk, P., Sapparapu, G., Lampley, R., Singh, V., Kose, N., Blum, D.L., Hughes, L.J., Satheshkumar, P.S., Townsend, M.B., Kondas, A.V., Reed, Z., Weiner, Z., Olson, V.A., Hammarlund, E., Raue, H.P., Slifka, M.K., Slaughter, J.C., Graham, B.S., Edwards, K.M., Eisenberg, R.J., Cohen, G.H., Joyce, S. and Crowe, J.E. 2016. Cross-neutralizing and protective human antibody specificities to poxvirus infections. Cell 167(3), 684–694.e9.

Gomez-Lucia, E. 2022. Monkeypox: some keys to understand this emerging disease. Animals 12(17), 2190.

Hakim, M.S. and Widyaningsih, S.A. 2023. The recent re-emergence of human monkeypox: would it become endemic beyond Africa? J. Infect. Public Health 16(3), 332–340.

Harapan, H., Ophinni, Y., Megawati, D., Frediansyah, A., Mamada, S.S., Salampe, M., Bin Emran, T., Winardi, W., Fathima, R., Sirinam, S., Sittikul, P., Stoian, A.M., Nainu, F. and Sallam, M. 2022. Monkeypox: a comprehensive review. Viruses 14(10), 2155.

Hasan, S. and Saeed, S. 2022. Monkeypox disease: an emerging public health concern in the shadow of COVID-19 pandemic: an update. Trop. Med. Infect. Dis. 7(10), 283.

Hatmal, M.M., Al-Hatamleh, M.A.I., Olaimat, A.N., Ahmad, S., Hasan, H., Suhaimi, N.A.A., Albakri, K.A., Alzyoud, A.A., Kadir, R. and Mohamud, R. 2022. Comprehensive literature review of monkeypox. Emerg. Microbes Infect. 11(1), 2600–2631.

Hernaez, B., Muñoz-Gómez, A., Sanchiz, A., Orviz, E., Valls-Carbo, A., Sagastagoitia, I., Ayerdi, O., Martín, R., Puerta, T., Vera, M., Cabello, N., Vergas, J., Prieto, C., Pardo-Figuerez, M., Negredo, A., Lagarón, J.M., Del Romero, J., Estrada, V. and Alcamí, A. 2023. Monitoring monkeypox virus in saliva and air samples in Spain: a cross-sectional study. Lancet Microbe. 4(1), e21–e28.

Hong, K.H., Kim, G.J., Roh, K.H., Lee, H., Park, O.K., Kim, T.S., Kim, J.S., Lee, J., Seong, M.W., Kim, S.Y., Park, J.S., Park, Y., Huh, H.J., Ryoo, N., Kim, H.S., Sung, H. and Yoo, C.K. 2023. Guidelines for the laboratory diagnosis of monkeypox in Korea. Ann. Lab. Med. 43(2), 137–144.

Huang, Y.A., Howard-Jones, A.R., Durrani, S., Wang, Z. and Williams, P.C. 2022. Monkeypox: a clinical update for paediatricians. J. Paediatr. Child Health 58(9), 1532–1538.

Hung, Y.P., Lee, C.C., Lee, J.C., Chiu, C.W., Hsueh, P.R. and Ko, W.C. 2022. A brief on new waves of monkeypox and vaccines and antiviral drugs for monkeypox. J. Microbiol. Immunol. Infect. 55(5), 795–802.

Hussain, A., Kaler, J., Lau, G. and Maxwell, T. 2022. Clinical conundrums: differentiating monkeypox from similarly presenting infections. Cureus 14(10), e29929.

Islam, M.A., Mumin, J., Haque, M.M., Haque, M.A., Khan, A., Bhattacharya, P. and Haque, M.A. 2023. Monkeypox virus (MPXV): a brief account of global spread, epidemiology, virology, clinical features, pathogenesis, and therapeutic interventions. Infect. Med. (Beijing) 2(4), 262–272.

Jain, A., Sturmlechner, I., Weyand, C.M. and Goronzy, J.J. 2023. Heterogeneity of memory T cells in aging. Front. Immunol. 14(1), 1250916.

Johnston, S.C., Johnson, J.C., Stonier, S.W., Lin, K.L., Kisalu, N.K., Hensley, L.E. and Rimoin, A.W. 2015. Cytokine modulation correlates with severity of monkeypox disease in humans. J. Clin. Virol. 63(1), 42–45.

Johri, N., Kumar, D., Nagar, P., Maurya, A., Vengat, M. and Jain, P. 2022. Clinical manifestations of human monkeypox infection and implications for outbreak strategy. Health Sci Rev (Oxf) 5(1), 100055.

Kaler, J., Hussain, A., Flores, G., Kheiri, S. and Desrosiers, D. 2022. Monkeypox: a comprehensive review of transmission, pathogenesis, and manifestation. Cureus 14(7), e26531.

Karagoz, A., Tombuloglu, H., Alsaeed, M., Tombuloglu, G., AlRubaish, A.A., Mahmoud, A., Smajlović, S., Ćordić, S., Rabaan, A.A. and Alsuhaimi, E. 2023. Monkeypox (mpox) virus: classification, origin, transmission, genome organization, antiviral drugs, and molecular diagnosis. J. Infect. Public Health 16(4), 531–541.

Kaswa, R., Nair, A. and Von Pressentin, K, B. 2022. The outbreak of monkeypox: a clinical overview. S. Afr. Fam. Pract. 64(1), e1–e5.

Kaushal, S.K. and Sinha, A.K. 2024. Modeling and stability analysis of the transmission dynamics of monkeypox with control intervention. Part. Diff. Eqns Appl. Math. 10, 100730.

Kenner, J., Cameron, F., Empig, C., Jobes, D.V. and Gurwith, M. 2006. LC16m8: an attenuated smallpox vaccine. Vaccine 24(47–48), 7009–7022.

Khamees, A., Awadi, S., Al-Shami, K., Alkhoun, H.A., Al-Eitan, S.F., Alsheikh, A.M., Saeed, A., Al-Zoubi, R.M. and Zoubi, M.S.A. 2023. Human monkeypox virus in the shadow of the COVID-19 pandemic. J. Infect. Public Health 16(8), 1149–1157.

Khattak, S., Rauf, M.A., Ali, Y., Yousaf, M.T., Liu, Z., Wu, D.D. and Ji, X.Y. 2023. The monkeypox diagnosis, treatments and prevention: a review. Front. Cell. Infect. Microbiol. 12(1), 1088471.

Koehler, H., Cotsmire, S., Zhang, T., Balachandran, S., Upton, J.W., Langland, J., Kalman, D., Jacobs, B.L. and Mocarski, E.S. 2021. Vaccinia virus E3 prevents sensing of Z-RNA to block ZBP1-dependent necroptosis. Cell Host Microbe 29(8), 1266–1276.e5.

Koenig, K.L., Beÿ, C.K. and Marty, A.M. 2022. Monkeypox 2022 identify-isolate-inform: a 3I tool for frontline clinicians for a zoonosis with escalating human community transmission. One Health 15(1), 100410.

Kulshrestha, S., Rastogi, A. and Goel, A. 2022. Monkeypox virus: lessons learnt. J. Pure Appl. Microbiol. 16(suppl 1), 3072–3082.

Kumar, N., Acharya, A., Gendelman, H.E. and Byrareddy, S.N. 2022. The 2022 outbreak and the pathobiology of the monkeypox virus. J. Autoimmun. 131(1), 102855.

Kumar, P., Chaudhary, B., Yadav, N., Devi, S., Pareek, A., Alla, S., Kajal, F., Nowrouzi-Kia, B., Chattu, V.K. and Gupta, M.M. 2023. Recent advances in research and management of human monkeypox virus: an emerging global health threat. Viruses 15(4), 937.

Lai, C.C., Hsu, C.K., Yen, M.Y., Lee, P.I., Ko, W.C. and Hsueh, P.R. 2022. Monkeypox: an emerging global threat during the COVID-19 pandemic. J. Microbiol. Immunol. Infect. 55(5), 787–794.

Lepelletier, D., Pozzetto, B., Chauvin, F., Chidiac, C. and High Council for Public Health national working groups. 2022. Management of patients with monkeypox virus infection and contacts in the community and in healthcare settings: a French position paper. Clin. Microbiol. Infect. 28(12), 1572–1577.

Letafati, A. and Sakhavarz, T. 2023. Monkeypox virus: a review. Microb. Pathog. 176(1), 106027.

Li, D., Wang, H., Sun, L., Feng, J., Li, W., Cheng, L., Liao, X., Zhang, Y., Xu, Z., Ge, X., Zhou, B., Zhao, J., Ju, B., Lu, H. and Zhang, Z. 2024b. Levels of antibodies against the monkeypox virus compared by HIV status and historical smallpox vaccinations: a serological study. Emerg. Microbes Infect. 13(1), 2356153.

Li, H., Huang, Q.Z., Zhang, H., Liu, Z.X., Chen, X.H., Ye, L.L. and Luo, Y. 2023. The land-scape of immune response to monkeypox virus. EBioMedicine 87(1), 104424.

Li, H., Zhang, H., Ding, K., Wang, X.H., Sun, G.Y., Liu, Z.X. and Luo, Y. 2022a. The evolving epidemiology of monkeypox virus. Cytokine Growth Factor Rev. 68(1), 1–12.

Li, Q., Chen, Y., Zhang, W., Li, C., Tang, D., Hua, W., Hou, F., Chen, Z., Liu, Y., Tian, Y., Sun, K., Xu, X., Zeng, Y., Xia, F., Lu, J. and Wang, Z. 2024a. Mpox virus Clade IIb infected Cynomolgus macaques via mimic natural infection routes closely resembled human mpox infection. Emerg. Microbes Infect. 13(1), 2332669.

Li, Z., Li, X.X., Chen, Y., Ruan, Q., Huang, X., Zhu, G. and Sun, J. 2022b. Persistence of monkeypox virus DNA in clinical specimens. J. Infect. 85(6), 702–769.

Liszewski, M.K., Leung, M.K., Hauhart, R., Buller, R.M., Bertram, P., Wang, X., Rosengard, A.M., Kotwal, G.J. and Atkinson, J.P. 2006. Structure and regulatory profile of the monkeypox inhibitor of complement: comparison to homologs in vaccinia and variola and evidence for dimer formation. J. Immunol. 176(6), 3725–3734.

Long, B., Koyfman, A., Gottlieb, M., Liang, S.Y., Carius, B.M., Chavez, S. and Brady, W.J. 2022. Monkeypox: a focused narrative review for emergency medicine clinicians. Am. J. Emerg. Med. 61(1), 34–43.

Lu, J., Xing, H., Wang, C., Tang, M., Wu, C., Ye, F., Yin, L., Yang, Y., Tan, W. and Shen, L. 2023. Mpox (formerly monkeypox): pathogenesis, prevention, and treatment. Signal Transduct. Target. Ther. 8(1), 458.

Lucena-Neto, F.D., Falcão, L.F.M., Vieira-Junior, A.S., Moraes, E.C.S., David, J.P.F., Silva, C.C., Sousa, J.R., Duarte, M.I.S., Vasconcelos, P.F.C. and Quaresma, J.A.S. 2023. Monkeypox virus immune evasion and eye manifestation: beyond eyelid implications. Viruses 15(12), 2301.

Lulli, L.G., Baldassarre, A., Mucci, N. and Arcangeli, G. 2022. Prevention, risk exposure, and knowledge of monkeypox in occupational settings: a scoping review. Trop. Med. Infect. Dis. 7(10), 276.

Lum, F.M., Torres-Ruesta, A., Tay, M.Z., Lin, R.T.P., Lye, D.C., Rénia, L. and Ng, L.F.P. 2022. Monkeypox: disease epidemiology, host immunity and clinical interventions. Nat. Rev. Immunol. 22(10), 597–613.

Luna, N., Ramírez, A.L., Muñoz, M., Ballesteros, N., Patiño, L.H., Castañeda, S.A., Bonilla-Aldana, D.K., Paniz-Mondolfi, A. and Ramírez, J.D. 2022. Phylogenomic analysis of the monkeypox virus (MPXV) 2022 outbreak: emergence of a novel viral lineage? Travel Med Infect. Dis. 49(1), 102402.

Luo, Q. and Han, J. 2022. Preparedness for a monkeypox outbreak. Infect. Med. (Beijing) 1(2), 124–134.

Malik, S., Ahmed, A., Ahsan, O., Muhammad, K. and Waheed, Y. 2023. Monkeypox virus: a comprehensive overview of viral pathology, immune response, and antiviral strategies. Vaccines (Basel) 11(8), 1345.

Manirambona, E., Lopez, J.C.F., Nduwimana, C., Okesanya, O.J., Mbonimpaye, R., Musa, S.S., Usman, A.H. and Lucero-Prisno, D.E. 2023. Healthcare workers and monkeypox: the case for risk mitigation. Int. J. Surg. Open 50(1), 100584.

Manivel, M., Venkatesh, A., Arunkumar, K., Prakash, R.M., Shyamsunder. 2024. A mathematical model of the dynamics of the transmission of monkeypox disease using fractional differential equations. Adv. Theory Simul. 7(9), 2400330.

Mann, B.A., Huang, J.H., Li, P., Chang, H.C., Slee, R.B., O’Sullivan, A., Anita, M., Yeh, N., Klemsz, M.J., Brutkiewicz, R.R., Blum, J.S. and Kaplan, M.H. 2008. Vaccinia virus blocks Stat1-dependent and Stat1-independent gene expression induced by type I and type II interferons. J. Interferon Cytokine Res. 28(6), 367–380.

Martínez, J.I., Montalbán, E.G., Bueno, S.J., Martínez, F.M., Juliá, A.N., Díaz, J.S., Marín, N.G., Deorador, E.C., Forte, A.N., García, M.A., Navarro, A.M.H., Morales, L.M., Rodríguez, M.J.D., Ariza, M.C., García, L.M.D., Pariente, N.M., Zarzuelo, M.R., Rodríguez, M.J.V., Peña, A.A., Baena, E.R., Benito, Á.M., Meixeira, A.P., Gavín, M.O., Pérez, M.Á.L. and Arnáez, AA. 2022. Monkeypox outbreak predominantly affecting men who have sex with men, Madrid, Spain, 26 April to 16 June 2022. Euro. Surveill. 27(27), 2200471.

Masood, W., Khan, H.A., Cheema, H.A., Shahid, A., Bilal, W., Kamal, M.A., Essar, M.Y., Ahmad, S. and Marzo, R.R. 2022. The past, present, and future of monkeypox: a rapid review regarding prevalence and prevention. Inquiry 59(1), 469580221139366.

Mbala, P.K., Huggins, J.W., Riu-Rovira, T., Ahuka, S.M., Mulembakani, P., Rimoin, A.W., Martin, J.W. and Muyembe, J.T. 2017. Maternal and fetal outcomes among pregnant women with human monkeypox infection in the Democratic Republic of Congo. J. Infect. Dis. 216(7), 824–828.

Meng, X. 2022. Clinical manifestations of the pharynx in human monkeypox. Travel. Med. Infect. Dis. 50(1), 102465.

Messina, M.D., Wolf, E.L., Kanmaniraja, D., Alpert, P.L. and Ricci, Z.J. 2022. Imaging features of anorectal proctitis in monkeypox infection. Clin. Imaging. 92(1), 109–111.

Mitjà, O., Ogoina, D., Titanji, B.K., Galvan, C., Muyembe, J.J., Marks, M. and Orkin, C.M. 2023. Monkeypox. Lancet 401(10370), 60–74.

Morgan, C.N., Whitehill, F., Doty, J.B., Schulte, J., Matheny, A., Stringer, J., Delaney, L.J., Esparza, R., Rao, A.K. and McCollum, A.M. 2022. Environmental persistence of monkeypox virus on surfaces in household of person with travel-associated infection, Dallas, Texas, USA, 2021. Emerg. Infect. Dis. 28(10), 1982–1989.

Mungmunpuntipantip, R. and Wiwanitkit, V. 2022. Smallpox vaccination discontinuation and monkeypox incidence in an African endemic region: a reanalysis on the relationship between the withdrawal of smallpox vaccine and subsequent morbidity. Am. J. Clin. Exp. Immunol. 11(5), 78–83.

Nagarajan, P., Howlader, A., Louis, L.R.P. and Rangarajalu, K. 2022. Outbreaks of human monkeypox during the COVID-19 pandemic: a systematic review for healthcare professionals. Iran. J. Microbiol. 14(6), 778–791.

Najimudeen, M., Chen, H.W.J., Jamaluddin, N.A., Myint, M.H. and Marzo, R.R. 2022. Monkeypox in pregnancy: susceptibility, maternal and fetal otcomes, and one health concept. Int. J. MCH AIDS 11(2), e594.

Nakanishi, K., Yoshimoto, T., Tsutsui, H. and Okamura, H. 2001. Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev. 12(1), 53–72.

Nisar, H., Saleem, O., Sapna, F., Sham, S., Perkash, R.S., Kiran, N., Anjali, F., Mehreen, A. and Ram, B. 2023. A narrative review on the monkeypox virus: an ongoing global outbreak hitting the non-endemic countries. Cureus 15(8), e43322.

Nolen, L.D., Osadebe, L., Katomba, J., Likofata, J., Mukadi, D., Monroe, B., Doty, J., Hughes, C.M., Kabamba, J., Malekani, J., Bomponda, P.L., Lokota, J.I., Balilo, M.P., Likafi, T., Lushima, R.S., Ilunga, B.K., Nkawa, F., Pukuta, E., Karhemere, S., Tamfum, J.J., Nguete, B., Wemakoy, E.O., McCollum, A.M. and Reynolds, M.G. 2016. Extended human-to-human transmission during a monkeypox outbreak in the Democratic Republic of the Congo. Emerg. Infect. Dis. 22(6), 1014–1021.

Nolen, L.D., Osadebe, L., Katomba, J., Likofata, J., Mukadi, D., Monroe, B., Doty, J., Kalemba, L., Malekani, J., Kabamba, J., Bomponda, P.L., Lokota, J.I., Balilo, M.P., Likafi, T., Lushima, R.S., Tamfum, J.J., Okitolonda, E.W., McCollum, A.M. and Reynolds, M.G. 2015. Introduction of monkeypox into a community and household: risk factors and Zoonotic Reservoirs in the Democratic Republic of the Congo. Am. J. Trop. Med. Hyg. 93(2), 410–415.

Nyame, J., Punniyakotti, S., Khera, K., Pal, R.S., Varadarajan, N. and Sharma, P. 2023. Challenges in the treatment and prevention of monkeypox infection; a comprehensive review. Acta Trop. 245(1), 106960.

O’Neill, M., LePage, T., Bester, V., Yoon, H., Browne, F. and Nemec, E.C. 2023. Mpox (Formally Known as Monkeypox). Physician Assist. Clin. 8(3), 483–494.

Ortiz-Martínez, Y., Rodríguez-Morales, A.J., Franco-Paredes, C., Chastain, D.B., Gharamti, A.A., Barahona, L.V. and Henao-Martínez, A.F. 2022. Monkeypox - a description of the clinical progression of skin lesions: a case report from Colorado, USA. Ther. Adv. Infect. Dis. 9(1), 20499361221117726.

Ortiz-Saavedra, B., León-Figueroa, D.A., Montes-Madariaga, E.S., Ricardo-Martínez, A., Alva, N., Cabanillas-Ramirez, C., Barboza, J.J., Siddiq, A., Cusicanqui, L.A.C., Bonilla-Aldana, D.K. and Rodriguez-Morales, A.J. 2022. Antiviral treatment against monkeypox: a scoping review. Trop. Med. Infect. Dis. 7(11), 369.

Osborn, L.J., Villarreal, D., Wald-Dickler, N. and Bard, J.D. 2022. Monkeypox: clinical considerations, epidemiology, and laboratory diagnostics. Clin. Microbiol. Newsl. 44(22), 199–208.

Pan, J., Fei, C.J., Hu, Y., Wu, X.Y., Nie, L. and Chen, J. 2023. Current understanding of the cGAS-STING signaling pathway: structure, regulatory mechanisms, and related diseases. Zool. Res. 44(1), 183–1218.

Parker, S. and Buller, R.M. 2013. A review of experimental and natural infections of animals with monkeypox virus between 1958 and 2012. Future Virol. 8(2), 129–157.

Peng, X., Wang, B., Li, Y., Chen, Y., Wu, X., Fu, L., Sun, Y., Liu, Q., Lin, Y.F., Liang, B., Fan, Y. and Zou, H. 2023. Perceptions and worries about monkeypox, and attitudes towards monkeypox vaccination among medical workers in China: a cross-sectional survey. J. Infect. Public Health 16(3), 346–353.

Pilna, H., Hajkova, V., Knitlova, J., Liskova, J., Elsterova, J. and Melkova, Z. 2021. Vaccinia virus expressing interferon regulatory factor 3 induces higher protective immune responses against lethal poxvirus challenge in atopic organism. Viruses 13(10), 1986.

Pinto, P., Costa, M.A., Gonçalves, M.F.M., Rodrigues, A.G. and Lisboa, C. 2023. Mpox person-to-person transmission-where have we got so far? A systematic review. Viruses 15(5), 1074.

Poland, G.A., Kennedy, R.B. and Tosh, P.K. 2022. Prevention of monkeypox with vaccines: a rapid review. Lancet Infect. Dis. 22(12), e349–e358.

Polk, C., Sampson, M., Fairman, R.T., DeWitt, M.E., Leonard, M., Neelakanta, A., Davidson, L., Roshdy, D., Branner, C., McCurdy, L., Ludden, T., Tapp, H. and Passaretti, C. 2023. Evaluation of a health system’s implementation of a monkeypox care model under the RE-AIM framework. Ther. Adv. Infect. Dis. 10(1), 20499361231158463.

Priyamvada, L., Carson, W.C., Ortega, E., Navarra, T., Tran, S., Smith, T.G., Pukuta, E., Muyamuna, E., Kabamba, J., Nguete, B.U., Likafi, T., Kokola, G., Lushima, R.S., Tamfum, J.M., Okitolonda, E.W., Kaba, D.K., Monroe, B.P., McCollum, A.M., Petersen, B.W., Satheshkumar, P.S. and Townsend, M.B. 2022. Serological responses to the MVA-based JYNNEOS monkeypox vaccine in a cohort of participants from the Democratic Republic of Congo. Vaccine 40(50), 7321–7327.

Quarleri, J., Delpino, M.V. and Galvan, V. 2022. Monkeypox: considerations for the understanding and containment of the current outbreak in non-endemic countries. Geroscience 44(4), 2095–2103.

Qudus, M.S., Cui, X., Tian, M., Afaq, U., Sajid, M., Qureshi, S., Liu, S., Ma, J., Wang, G., Faraz, M., Sadia, H., Wu, K. and Zhu, C. 2023. The prospective outcome of the monkeypox outbreak in 2022 and characterization of monkeypox disease immunobiology. Front. Cell. Infect. Microbiol. 13(1), 1196699.

Rabaan, A.A., Al-Shwaikh, S.A., Alfouzan, W.A., Al-Bahar, A.M., Garout, M., Halwani, M.A., Albayat, H., Almutairi, N.B., Alsaeed, M., Alestad, J.H., Al-Mozaini, M.A., Ashgar, T.M.A., Alotaibi, S., Abuzaid, A.A., Aldawood, Y., Alsaleh, A.A., Al-Afghani, H.M., Altowaileb, J.A., Alshukairi, A.N., Arteaga-Livias, K., Singh, K.K.B. and Imran, M. 2023. A comprehensive review on monkeypox viral disease with potential diagnostics and therapeutic options. Biomedicines 11(7), 1826.

Raccagni, A.R., Candela, C., Mileto, D., Canetti, D., Bruzzesi, E., Rizzo, A., Castagna, A. and Nozza, S. 2022. Monkeypox infection among men who have sex with men: PCR testing on seminal fluids. J. Infect. 85(5), 573–607.

Raccagni, A.R., Mancon, A., Diotallevi, S., Lolatto, R., Bruzzesi, E., Gismondo, M.R., Castagna, A., Mileto, D. and Nozza, S. 2024. Monkeypox virus neutralizing antibodies at six months from Mpox infection: virologic factors sssociated with poor immunologic response. Viruses 16(5), 681.

Rajsri, K.S. and Rao, M. 2022. Poxvirus-driven human diseases and emerging therapeutics. Ther. Adv. Infect. Dis. 9(1), 20499361221136751.

Rehm, K.E., Connor, R.F., Jones, G.J., Yimbu, K. and Roper, R.L. 2010. Vaccinia virus A35R inhibits MHC class II antigen presentation. Virology 397(1), 176–186.

Reina, J. and Iglesias, C. 2023. Vaccines against monkeypox. Med. Clin. (Engl Ed) 160(7), 305–309.

Riopelle, J.C., Munster, V.J. and Port, J.R. 2022. Atypical and unique transmission of monkeypox virus during the 2022 outbreak: an overview of the current state of knowledge. Viruses 14(9), 2012.

Rodríguez-Cuadrado, F.J., Nájera, L., Suárez, D., Silvestre, G., García-Fresnadillo, D., Roustan, G., Sánchez-Vázquez, L., Jo, M., Santonja, C., Garrido-Ruiz, M.C., Vicente-Montaña, A.M., Rodríguez-Peralto, J.L. and Requena, L. 2023. Clinical, histopathologic, immunohistochemical, and electron microscopic findings in cutaneous monkeypox: a multicenter retrospective case series in Spain. J. Am. Acad. Dermatol. 88(4), 856–863.

Rosa, R.B., de Castro, E.F., da Silva, M.V., Ferreira, D.C.P., Jardim, A.C.G., Santos, I.A., Marinho, M.D.S., França, F.B.F. and Pena, L.J. 2023. In vitro and in vivo models for monkeypox. iScience 26(1), 105702.

Russo, A.T., Grosenbach, D.W., Chinsangaram, J., Honeychurch, K.M., Long, P.G., Lovejoy, C., Maiti, B., Meara, I. and Hruby, D.E. 2021. An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications. Expert. Rev. Anti Infect. Ther. 19(3), 331–344.

Saadh, M.J., Ghadimkhani, T., Soltani, N., Abbassioun, A., Pecho, R.D.C., Taha, A., Kazem, T.J., Yasamineh, S. and Gholizadeh, O. 2023. Progress and prospects on vaccine development against monkeypox infection. Microb. Pathog. 180(1), 106156.

Saghazadeh, A. and Rezaei, N. 2022. Poxviruses and the immune system: implications for monkeypox virus. Int. Immunopharmacol. 113(Pt A), 109364.

Sah, R., Humayun, M., Baig, E., Farooq, M., Hussain, H.G., Shahid, M.U., Cheema, H.A., Chandran, D., Yatoo, M.I., Sharma, A.K. and Dhama, K. 2022b. FDA’s authorized “JYNNEOS” vaccine for counteracting monkeypox global public health emergency; an update - correspondence. Int. J. Surg. 107(1), 106971.

Sah, R., Mohanty, A., Abdelaal, A., Reda, A., Rodriguez-Morales, A.J. and Henao-Martinez, A.F. 2022a. First Monkeypox deaths outside Africa: no room for complacency. Ther. Adv. Infect. Dis. 9(1), 20499361221124027.

Sah, R., Paul, D., Mohanty, A., Shah, A., Mohanasundaram, A.S. and Padhi, B.K. 2023. Monkeypox (Mpox) vaccines and their side effects: the other side of the coin. Int. J. Surg. 109(2), 215–217.

Saied, A.A., Dhawan, M., Metwally, A.A., Fahrni, M.L., Choudhary, P. and Choudhary, O.P. 2022. Disease history, pathogenesis, diagnostics, and therapeutics for human monkeypox disease: a comprehensive review. Vaccines (Basel) 10(12), 2091.

Sasani, T.A., Cone, K.R., Quinlan, A.R. and Elde, N.C. 2018. Long read sequencing reveals poxvirus evolution through rapid homogenization of gene arrays. Elife 7(1), e35453.

Schmidle, P., Leson, S., Wieland, U., Böer-Auer, A., Metze, D. and Braun, S.A. 2023. Lives of skin lesions in monkeypox: histomorphological, immunohistochemical, and clinical correlations in a small case series. Viruses 15(8), 1748.

Schwartz, D.A. and Pittman, P.R. 2023. Mpox (Monkeypox) in pregnancy: viral clade differences and their associations with varying obstetrical and fetal outcomes. Viruses 15(8), 1649.

Sharma, K., Akre, S., Chakole, S. and Wanjari, M.B. 2022. Monkeypox: an emerging disease. Cureus 14(9), e29393.

Sharma, R., Chen, K.T. and Sharma, R. 2023. Emerging evidence on monkeypox: resurgence, global burden, molecular insights, genomics and possible management. Front. Cell. Infect. Microbiol. 13(1), 1134712.

Shchelkunov, S.N. 2012. Orthopoxvirus genes that mediate disease virulence and host tropism. Adv. Virol. 2012(1), 524743.

Shchelkunova, G.A. and Shchelkunov, S.N. 2022. Smallpox, monkeypox and other human orthopoxvirus infections. Viruses 15(1), 103.

Singhal, T., Kabra, S.K. and Lodha, R. 2022. Monkeypox: a review. Indian J. Pediatr. 89(10), 955–960.

Skopelja-Gardner, S., An, J. and Elkon, K.B. 2022. Role of the cGAS-STING pathway in systemic and organ-specific diseases. Nat. Rev. Nephrol. 18(9), 558–572.

Sobral-Costas, T.G., Escudero-Tornero, R., Servera-Negre, G., Bernardino, J.I., Arroyo, A.G., Díaz-Menéndez, M., Busto-Leis, J.M., Álvarez, P.R., Pinto, P.H. and Cudos, E.S. 2023. Human monkeypox outbreak: epidemiological data and therapeutic potential of topical cidofovir in a prospective cohort study. J. Am. Acad. Dermatol. 88(5), 1074–1082.

Song, H., Josleyn, N., Janosko, K., Skinner, J., Reeves, R.K., Cohen, M., Jett, C., Johnson, R., Blaney, J.E., Bollinger, L., Jennings, G. and Jahrling, P.B. 2013. Monkeypox virus infection of rhesus macaques induces massive expansion of natural killer cells but suppresses natural killer cell functions. PLoS One 8(10), e77804.

Srivastava, S., Kumar, S., Jain, S., Mohanty, A., Thapa, N., Poudel, P., Bhusal, K., Al-Qaim, Z.H., Barboza, J.J., Padhi, B.K. and Sah, R. 2023. The global monkeypox (Mpox) outbreak: a comprehensive review. Vaccines (Basel) 11(6), 1093.

Stenglein, M.D., Burns, M.B., Li, M., Lengyel, J. and Harris, R.S. 2010. APOBEC3 proteins mediate the clearance of foreign DNA from human cells. Nat. Struct. Mol. Biol. 17(2), 222–229.

Swed, S., Alibrahim, H., Bohsas, H., Jawish, N., Rais, M.A., Nasif, M.N., Hafez, W., Sawaf, B., Abdelrahman, A., Fathey, S., Ibrahim, I.A.I.A., Almashaqbeh, S.H.A., Aljawarneh R.M.Y., Rakab, A., El-Shafei, E.H.H., Hurlemann, R., Elsayed, M.E.G. and Data Collection Group. 2023. A multinational cross-sectional study on the awareness and concerns of healthcare providers toward monkeypox and the promotion of the monkeypox vaccination. Front. Public Health 11(1), 1153136.

Titanji, B.K., Tegomoh, B., Nematollahi, S., Konomos, M. and Kulkarni, P.A. 2022. Monkeypox: a contemporary review for healthcare professionals. Open Forum Infect. Dis. 9(7), ofac310.

Tumewu, J., Wardiana, M., Ervianty, E., Sawitri, Rahmadewi, Astindari, Anggraeni, S., Widia, Y., Amin, M., Sulichah, S.R.O., Kuntaman, K., Juniastuti and Lusida, M.I. 2020. An adult patient with suspected of monkeypox infection differential diagnosed to chickenpox. Infect. Dis. Rep. 12(Suppl 1), 8724.

Ullah, M., Li, Y., Munib, K. and Zhang, Z. 2023. Epidemiology, host range, and associated risk factors of monkeypox: an emerging global public health threat. Front. Microbiol. 14(1), 1160984.

Upadhayay, S., Arthur, R., Soni, D., Yadav, P., Navik, U., Singh, R., Singh, T.G. and Kumar, P. 2022. Monkeypox infection: the past, present, and future. Int. Immunopharmacol. 113(Pt A), 109382.

Venkatesh, A., Manivel, M., Arunkumar, K., Prakash Raj, M., Shyamsunder, and Purohit, S.D. 2024. A fractional mathematical model for vaccinated humans with the impairment of monkeypox transmission. Eur. Phys. J. Spec. Top. 233(6); doi:10.1140/epjs/s11734-024-01211-5.

Vierbaum, L., Wojtalewicz, N., Kaufmann, A., Goseberg, S., Kaiser, P., Grunert, H.P., Dühring, U., Zimmermann, A., Scholz, A., Michel, J., Nitsche, A., Rabenau, H.F., Obermeier, M., Schellenberg, I., Zeichhardt, H. and Kammel, M. 2023. Results of the first German external quality assessment scheme for the detection of monkeypox virus DNA. PLoS One 18(4), e0285203.

Wang, N., Zheng, Y. and Wang, L. 2022. Can monkeypox virus be transmitted through the air? - Correspondence. Int. J. Surg. 108(1), 106995.

Wang, X. and Lun, W. 2023. Skin manifestation of human monkeypox. J. Clin. Med. 12(3), 914.

Watanabe, Y., Kimura, I., Hashimoto, R., Sakamoto, A., Yasuhara, N., Yamamoto, T., Genotype to Phenotype Japan (G2P-Japan) Consortium, Sato, K. and Takayama, K. 2023. Virological characterization of the 2022 outbreak-causing monkeypox virus using human keratinocytes and colon organoids. J. Med. Virol. 95(6), e28827.

White, S.D. and Jacobs, B.L. 2012. The amino terminus of the vaccinia virus E3 protein is necessary to inhibit the interferon response. J. Virol. 86(10), 5895–5904.

World Health Organization. 2024. 2022-24 mpox (monkeypox) outbreak: global trends. Available via https://www.who.int/emergencies/situations/mpox-outbreak

Wong, L., Gonzales-Zamora, J.A., Beauchamps, L., Henry, Z. and Lichtenberger, P. 2022. Clinical presentation of monkeypox among people living with HIV in South Florida: a case series. Infez. Med. 30(4), 610–618.

Xiang, Y. and White, A. 2022. Monkeypox virus emerges from the shadow of its more infamous cousin: family biology matters. Emerg. Microbes. Infect. 11(1), 1768–1777.

Yan, K., Tang, L.K., Xiao, F.F., Zhang, P., Lu, C.M., Hu, L.Y., Wang, L.S., Cheng, G.Q. and Zhou, W.H. 2023. Monkeypox and the perinatal period: what does maternal-fetal medicine need to know? World J. Pediatr. 19(3), 213–223.

Yi, X.M., Lei, Y.L., Li, M., Zhong, L. and Shu Li, S. 2024. The monkeypox virus-host interplays. Cell Insight 3(5), 100185.

Zahmatyar, M., Fazlollahi, A., Motamedi, A., Zolfi, M., Seyedi, F., Nejadghaderi, S.A., Sullman, M.J.M., Mohammadinasab, R., Kolahi, A.A., Arshi, S. and Safiri, S. 2023. Human monkeypox: history, presentations, transmission, epidemiology, diagnosis, treatment, and prevention. Front. Med. (Lausanne) 10(1), 1157670.

Zandi, M., Shafaati, M. and Hosseini, F. 2023. Mechanisms of immune evasion of monkeypox virus. Front. Microbiol. 14(1), 1106247.

Zhang, J.M. and An, J. 2007. Cytokines, inflammation, and pain. Int. Anesthesiol. Clin. 45(2), 27–37.

Zheng, Q., Bao, C., Li, P. and Pan, Q. 2022. Projecting the global spread of the 2022 monkeypox outbreak considering population mobility. Travel Med. Infect. Dis. 50(1), 102445.F

Zhu, J., Yu, J., Qin, H., Chen, X., Wu, C., Hong, X., Zhang, Y. and Zhang, Z. 2023. Exploring the key genomic variation in monkeypox virus during the 2022 outbreak. BMC Genom. Data 24(1), 67.