Monkeypox virus: A review

Abstract

While monkeypox was previously found in Africa, the bulk of occurrences in the present outbreak are being reported in many countries. It is not yet known how this outbreak began, and as the COVID-19 crisis begins to abate, numerous nations throughout the world are now contending with a novel outbreak. Monkeypox is a transmissible virus between animals and humans, belonging to the Orthopoxvirus genus of the Poxviridae family. In the 1970s, cases of monkeypox began increasing due to the cessation of vaccination against smallpox, which drew international attention. The virus was named monkeypox because it was first observed in macaque monkeys. It is thought to be transmitted by several different rodents and small mammals, though the origin of the virus is not known. Monkeypox, while occasionally transmitted from one human to another, can be disseminated through the inhalation of droplets or through contact with the skin lesions of an infected individual. Unfortunately, there is no definitive cure for monkeypox; however, supportive care can be offered to ameliorate its symptoms. In severe cases, medications like tecovirimat may be administered. However, there are no established guidelines for symptom management in monkeypox cases. In this article we have discussed about different aspects of monkeypox including viral structure, transmission, replication, clinical manifestations, vaccination, treatment and current prevalence in the world to understand it better and give insight to the future studies.

1. Introduction

There have been many viral epidemics throughout human history that have had significant impacts on global health and society. Some of the most well-known viruses responsible for epidemics includes smallpox, Influenza, Human Immunodeficiency virus-1 (HIV-1), Ebola, severe acute respiratory syndrome (SARS), severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) and the last one is monkeypox virus. Smallpox was a virulent and fatal illness induced by the variola virus, which posed a grave threat to humanity [1]. HIV is ssRNA virus belonging to retroviridae and is responsible for AIDS disease. Retroviridae are family of viruses that mostly attacks the immune system, leaving people vulnerable to other infections and diseases. Acquired Immune Deficiency Syndrome (AIDS) is a medical condition that occurs when the body's immune system is severely weakened, leaving it unable to effectively defend against disease and infection. HIV/AIDS has become one of the most devastating pandemics in history, with an estimated 35 million deaths worldwide [2]. Influenza, commonly known as the flu, is a respiratory illness virus belonging to orthomixoviridae family. It is highly contagious and can lead to severe illness and death, particularly in older people and those with underlying health conditions. There have been several influenza pandemics throughout history, including the Spanish flu pandemic in 1918–1919, which is estimated to have infected one third of the world's population and caused tens of millions of deaths [3,4]. Ebola is ssRNA virus belonging to Filoviridae and is responsible for a viral disease that causes severe fever, bleeding, and organ failure. It is transmitted through contact with the blood or bodily fluids of infected animals or people. There have been several outbreaks of Ebola in Africa, with the most recent one occurring in West Africa in 2014–2016, resulting in over 28,000 cases and over 11,000 deaths [5]. SARS is a acte viral respiratory illness caused by the SARS-CoV virus. It is ssRNA virus belonging to coronaviridae family. It was first identified in 2002 in China and spread to other countries, resulting in over 8000 cases and over 750 deaths [6]. SARS-CoV-2 is next member of coronaviridae family responsible for COVID-19 pandemic. It is a highly infectious respiratory disease and is transmitted through aerosols and droplets. It was first identified in Wuhan, China in December 2019 and has since spread to become a global pandemic [7]. Lastly a virus of poxviridae family which is the Monkeypox virus. Monkeypox is a rare viral disease caused by a virus belonging to the poxviridae family, which has a double-stranded DNA. It is contracted by humans through infected animals like monkeys, rats, and squirrels. The virus can spread to humans through close contact with bodily fluids from a carrier, such as saliva, mucus, or skin lesions. The illness presents with symptoms like fever, headache, muscle pain, and a rash that starts as small bumps and evolves into raised bumps filled with fluid. Bumps caused by monkeypox may manifest anywhere on the body, but are usually found on the face, hands, and feet. In extreme cases, the infection may lead to dangerous complications such as pneumonia and sepsis, which can potentially become fatal. There is currently no specific treatment for monkeypox, but supportive care, such as medications to reduce fever and pain, can be helpful in managing the symptoms. The smallpox vaccine can provide some protection against monkeypox, but it is not always effective. To avoid contracting monkeypox, it is essential to abstain from contact with affected animals, as well as practicing proper hygiene, such as washing one's hands regularly and avoiding close contact with those who are ill [8]. In this article, we have talked about different aspects of monkeypox. Our aim of this study was to investigate about monkeypox virus. The search strategy was performed in PubMed, NCBI, Google Scholar, EMBASE and Medline from 1975 to 2023. We removed the duplicated articles with the same content. Then we assessed the remaining articles' full text precisely for the competency (see Table 1 , Fig. 1 ).

Table 1.

Comparing different vaccines that are currently in use in different countries by type, route of administration, target group and recommended number of doses [[73], [74], [75], [76]]

Number	Vaccine	Type	Route of administration	Recommended number of doses
1	ACAM2000	Live attenuated (2nd generation)	Percutaneously	single dose
2	JYNNEOSTM/MVA-BN	Vaccinia virus (Ankara strain) containing MPX antigens (3rd generation)	Subcutaneously	2 doses within 28 days
3	LC-16	Live attenuated (3rd generation)	Percutaneously	2 doses within 28 days

Fig. 1.

Pathogenesis and common clinical manifestations of monkeypox virus. The virus is transmitted through droplets and has 7–21 (Average 14) days of incubation period. During this stage, infected person is not able to transmit the infection to others. After this stage, Viremia happens and clinical manifestations appear. In this stage, person can transmit the infection and spread the virus in the community. However, Monkeypox is less contagious than smallpox and causes less severe illness. Fever and other prodromal symptoms (e.g., chills, lymphadenopathy, malaise, myalgias, or headache) can occur before rash but either may occur after rash or not be present at all.

2. Results

2.1. History

The first case of Monkeypox occurred in a 9-month-old child in the Democratic Republic of the Congo in 1970. The virus gained substantial prominence in 2003–2004, following an outbreak in the United States [9]. Clinical manifestations following monkeypox infection is similar to smallpox [10]. However, Monkeypox is typically less lethal. The global attention to Monkeypox rose in the 1970s, following the eradication of smallpox, as the incidence of the virus increased due to the cessation of smallpox vaccination programs. The virus was named after its initial observation in macaque monkeys, though it is not actually transmitted by these primates. Instead, transmission is believed to occur through various rodent and small mammal species, although the exact origin of the virus remains uncertain. Prior to 1970, the occurrence of the virus was only documented in non-human hosts. However, this perception was revised following the 2003 outbreak in the United States The 2003 Monkeypox outbreak in the United States revealed an increased level of transmissibility among human hosts, as well as a higher level of viremia in infected patients [11,12]. Historically, the majority of Monkeypox cases were reported in Africa, however, the current outbreak is predominantly being reported in western hemisphere and europe. The source of this outbreak remains unclear and various organizations are conducting contact tracing efforts to try to determine its origin.

2.2. Viral structure

The Poxviridae family constitutes a group of viruses characterized by their large size, enveloped structure, and double-stranded DNA. These viruses are commonly found in rodent, rabbit, and non-human primate populations [13]. The Poxviridae family is divided into two subfamilies: Entomopoxvirinae and Chordopoxvirinae. The Entomopoxvirinae subfamily encompasses viruses that infect insects, while the Chordopoxvirinae subfamily encompasses viruses that infect vertebrates. The Chordopoxvirinae subfamily is further divided into 18 genera, each of which encompasses multiple viruses, with a majority of them being of zoonotic origin [14,15] Monkeypox is a type of virus that can be passed from animals to humans. It belongs to the Orthopoxvirus genus within the Poxviridae family. The virus has an envelope and an uneven form, featuring a core in the shape of a dumbbell and additional bodies along the sides [[16], [17], [18]]. Poxviruses reproduce in the cytoplasm of cells, rather than the nucleus where most DNA viruses tend to replicate. During replication, poxviruses utilize a large number of their own encoded proteins, rather than relying on cellular proteins [[17], [18], [19]]. The central area of the poxvirus genome holds genes that plays a crucial role, such as transcription of the virus within the cell and assembly. Meanwhile, the genes located at the ends of the genome are participated in the interactions between the virus and its host [17,20]. 49 genes out of 150 are present in all sequenced members of the Poxviridae family, and 90 are present in the Chordopoxvirus subfamily [21]. A majority of conserved genes are in the central region of the genome [17]. Because of their large size, poxviruses such as Monkeypox face challenges in efficiently bypassing host defenses and rapidly replicating. Poxviruses are more likely to elicit an immune response from the host due to their increased exposure to the host's immune system. To avoid detection, poxviruses have evolved a collection of virulence genes that produce molecules with the ability to regulate the host's immune response [22,23]. These proteins can be divided into two categories based on where they act: intracellular or extracellular. Intracellular proteins include virotransducer proteins that hinder the cell's response to the infection and virostealth proteins that reduce the visibility of immune recognition markers, like Major Histocompatibility Complex 1 and CD4 [17,22,23]. The only type of extracellular protein is referred to as a viromimic protein. Viromimic proteins are subclassified into two categories: viroreceptors, which bind host cytokines and chemokines to interfere and disrupt their functions, and virokines, which imitate host cytokines, chemokines, and growth factors to enhance viral replication and dissemination [10,22,23]. Poxviruses, including monkeypox, employ modulatory proteins to hide from the body immune system and promote viral replication. The replication process of these viruses is distinctive and consists of various stages, beginning with attachment to host cells and culminating in the release of the virus from the infected cells. Poxviruses have two forms: mature virions (MVs) and extracellular enveloped virions (EVs). MVs have a single membrane and are responsible for attaching to host cells, while EVs have an additional outer membrane and facilitate the spread of the virus within the host. The process of fusion with the host cell membrane depends on several transmembrane proteins, and the stability of the MV or EV plays a role in transmission between host animals and spread within the host [18,19,24]. Poxvirus DNA replication occurs within cytoplasmic structures called factories, which derive from one infecting particle [25]. During the initial phase of the viral infection, compact structures known as factories are observed, which are composed of a core of DNA material encased within membranes [24,25]. As replication progresses, the viral factories enlarge and exhibit a more heterogeneous morphology, characterized by the formation of cavities that encompass both viral mRNA and host translation machinery [25,26]. In the later stage of replication, a mixture of viral gene products and membrane formation proteins form a complex that breaks down the membranes of the surrounding endoplasmic reticulum. This results in the formation of crescent-shaped structures that are utilized for the assembly of immature virion (IV) [26]. During the final stages of the replication cycle, the formation of immature virions (IVs) is facilitated by cooperation between late gene products of the virus and viral membrane assembly proteins. This complex causes the breakdown of the endoplasmic reticulum membranes, resulting in the formation of crescent-shaped structures. The mature virions (MVs), the most common infectious form of the virus, are produced by processing the IVs and leave the host cell by merging with the cytoplasmic membrane [25].

2.3. Pathogenesis of viral infection

The monkeypox virus can be classified into two main genetic groups, which are the central African (Congo Basin) group and the West African group. The central African (Congo Basin) group has been observed to exhibit higher virulence and cause more severe forms of the disease compared to the West African group [12,27].

Genetic comparisons between West and central African strains of the monkeypox virus have revealed specific genes that may contribute to the observed disparities in virulence between the two groups. The West African strains have deletions and fragments in certain open reading frames that may contribute to their reduced virulence [12,28]. Studies have demonstrated that Central African monkeypox virus impairs T-cell activation and inhibits the release of cytokines associated with inflammation in infected human cells [29].

The central African strain of the monkeypox virus has shown the capability to hinder T-cell activation and decrease the release of inflammatory cytokines in human cells during infection. Furthermore, this strain seems to selectively undermine host immunity by reducing apoptosis and inhibiting the transcription of specific genes associated with immunity. There is evidence that the virus can spread from animals to other animals and then to humans, as seen in the 2003 outbreak in the US Midwest, where it is believed that pet prairie dogs contracted the virus from rodents imported from Ghana that had already been infected [30,31]. The reservoir host of the monkeypox virus remains uncertain, however, indications suggest that monkeys and humans may be occasional hosts, while the virus's origin may be traced to certain species of rodents or squirrels found in the secondary forests of central Africa [32,33]. The transmission and subsequent establishment of monkeypox virus in a host involve a series of events that result in pathogenesis and pathophysiology. The transmission of the virus can occur through respiratory droplets during human-to-human transmission, or through direct contact with contaminated objects or surfaces, or mucocutaneous lesions of an infected individual. Human-to-human transmission is rare but it is possible. However, and the primary mode of transmission is believed to be from an animal host [30]. The virus enters the body by exposing the oral or respiratory mucosa and multiplies at the point of inoculation. This causes the virus to spread to nearby lymph nodes during the primary viremia stage, and later to far-off lymph nodes and organs during the secondary viremia stage through circulation. The incubation period, which is the time between exposure to the virus and the onset of symptoms, typically lasts between 7 and 21 days [[34], [a], [b]]. Clinical manifestations of monkeypox do not appear in this period, and the person infected cannot spread the virus to others in this stage. As the virus spreads in the body through secondary viremia, the prodromal stage begins. This stage is characterized by symptoms such as skin rashes and swollen lymph nodes, and the infected individual is considered to be highly contagious [[34], [a], [b]]. During the incubation period, no visible symptoms of monkeypox infection are present and the individual is not contagious. Approximately one to two weeks after infection, the individual begins to experience common symptoms including fever and muscle aches. These symptoms can often be misdiagnosed as the flu or a common cold. As the immune system activates, lymph nodes in various regions, including the maxilla, neck, and groin, may become enlarged, marking the start of the prodromal stage. During this stage, the individual is most contagious as they exhibit symptoms such as skin lesions and swollen lymph nodes [22]. During the course of infection with monkeypox virus, a rash is typically observed several days after the appearance of symptoms such as fever and swollen lymph nodes. This rash typically starts to appear on the face before spreading outwards [[34], [a], [b]]. In a typical case of monkeypox infection, rashes develop around 1–3 days after the onset of fever and swollen lymph nodes. These rashes generally start on the face and spread in the body, with more rashes appearing on the limbs and face than on the trunk and abdomen. The presence of these skin lesions can lead to difficulties in eating and drinking and malnutrition. Additionally, patients with these skin lesions are susceptible to secondary bacterial infections, but mainly happens in unvaccinated patients [12,35]. The hallmark symptom of monkeypox is the development of a skin rash that goes through various stages before ultimately resolving. During the course of the illness, the appearance of the skin rash is a distinctive hallmark and can be observed as a progression of lesions starting in the oral area, spreading to other parts of the body, and taking various forms including papules, blisters, and pustules before finally crusting and peeling off [12,36]. These lesions will eventually crust over within a period of two to three weeks [37]. The rash caused by monkeypox is a hallmark of the disease and undergoes a characteristic progression. It begins as lesions in the mouth and tongue, known as enanthem, before developing into papules, vesicles, and pustules. The rash can be painful during its different stages and can result in scarring, hyperpigmentation or hypopigmentation after it heals. Histopathological studies of early stages of the rash in humans have revealed damage to the epidermis and upper layer of the dermis, as well as inflammation and destruction of sebaceous glands and hair follicles, known as partial-thickness wounds. This type of skin lesion may lead to additional problems such as infections caused by bacteria and inflammation of the soft tissue under the skin [38,39]. Studies have demonstrated that the application of moist, sealed dressings can aid in the healing of lesions, and this method may also be beneficial in treating individuals with extensive facial rash caused by monkeypox [38,40].

2.4. Immunology

It is known that various orthopoxviruses, including monkeypox, share similar genetic and antigenic characteristics [18]. This implies that prior infection with a virus within the same genus can confer protection against subsequent infections with a different virus of the same genus due to cross-immunity [22,38]. Previously, getting vaccinated against smallpox was known to offer some level of defense against monkeypox. However, since the smallpox vaccine was discontinued after smallpox was eradicated in the 1970s, the cross-protection has gradually weakened [23,27]. Individuals who are less than 50 years old are at a higher risk of being infected by orthopoxviruses like monkeypox as they may not have received the smallpox vaccine, which was discontinued after the eradication of smallpox in the 1970s, reducing the level of cross-protection [25]. The decline in the incidence of human monkeypox in central Africa was likely due to widespread vaccination against smallpox during the global eradication campaign. However, the lack of immunity in individuals born after the elimination of smallpox has contributed to the reemergence of MPXV [30,41].

2.5. Epidemiology

The Monkeypox Virus (MPXV) is a neglected tropical pathogen found in various regions of sub-Saharan Africa and has a documented history of infecting humans. In the following years, numerous confirmed cases of human monkeypox were reported in Nigeria, including 10 cases between 1971 and 1978. Over the past three decades, the number of reported human cases of monkeypox has elevated [42]. The largest recorded outbreak of the West African strain of monkeypox (clade II) took place in Nigeria in the year 2017 [43]. Between 1970 and 1979, 38 of the 47 reported cases of monkeypox in West and Central Africa were concentrated in remote and rural areas of the Democratic Republic of the Congo [44]. During the time period between 1970 and 1971, Sierra Leone, Liberia, and Nigeria, which previously had no reported cases of smallpox, saw a sudden emergence of six cases of monkeypox in unvaccinated individuals [45].

Interestingly, in recent years, monkeypox outbreaks are occurring in regions where the disease was not previously found [[46], [47], [48]]. The occurrence of MPXV outside of its endemic regions is not a rare occurrence. There have been several outbreaks reported in non-endemic areas, including the United States in 2003 and the United Kingdom, Israel, and Singapore in 2017. These outbreaks have mainly been linked to travelers returning from endemic regions or to nosocomial exposure, such as contact with infected rodents [49,50]. However, the magnitude of the current outbreak of MPX differs from previous outbreaks in terms of its scope and rapid spread. By August 5, 2022, a minimum of 88 nations or territories had reported human-to-human transmission of the virus, with this number continuously increasing [51]. The sudden surge in MPXV cases in countries where it is not typically found has sparked fears of a potential pandemic. Diagnosing and treating MPXV is challenging due to the ways it can be transmitted, such as through close contact with an infected person or via droplets. This prompted WH to issue a Public Health Emergency of International Concern [52]. The recent global outbreak of monkeypox, a zoonotic disease, has sparked concern about the need for updated information as the world faces a pandemic. The current transmission pattern indicates that most cases of monkeypox are occurring in Europe and the Americas. The first outbreak of monkeypox which was outside of Africa was reported in Europe on May 2022, and rapidly spread to other countries. As of August 5, 2022, a worldwide outbreak of monkeypox has been reported with a total of 28,220 confirmed cases in 88 countries and an additional 1685 suspected cases. The first case in United States was reported on May 18, and shortly after that, there were newly infected patients in Australia, Israel and Brazil [53]. During the months of May and June in the year 2022, a significant number of confirmed cases of Monkeypox (MPXV) were reported, with an estimated total of 6000 cases. However, there was a significant elevated numbers of infected patients in July 2022, with approximately 17,000 cases reported. The trend of increasing MPX cases continued into August 2022, with over 5000 cases reported in the first five days of the month. Sadly, fatalities due to MPX have been recorded in three countries that were previously considered non-endemic (Brazil, Spain, and India) [54]. As of 2022, isolated cases of Monkeypox (MPX) in North America and Europe have been traced to the pet trade and travel from endemic regions. In May of the same year, cases of spontaneous MPXV infections were reported in Europe and the United States, primarily impacting men who engage in sexual activity with other men. There is no established epidemiological connection to the Central or West African regions. As of September 21, 2022, the majority of MPXV cases have been reported in the United States [55]. A recent analysis of the individuals affected by the ongoing global outbreak of Monkeypox Virus (MPXV) revealed that the majority of cases (97.4%) were among men, with a median age of 35 years. The sexual orientation of the majority of patients (97.5%) was identified as male who had sex with men, with only 1% identifying as bisexual. A recent study conducted in France also confirmed the presence of asymptomatic MPXV in anorectal samples from male individuals who have sex with men [56]. A majority of confirmed cases of Monkeypox (MPXV) have been reported in Europe and the Americas, with 14 countries (including UK, Spain, Germany, France, Portugal, Italy, Switzerland, Belgium, US, Mexico, Canada, Netherlands, Brazil, and Peru) accounting for more than 90% of all reported cases. Meanwhile, only 345 cases have been reported in seven African countries where MPXV has been endemic in the past. Conversely, there have been 27,875 cases reported in non-endemic countries. On the other hand, Asian countries and those in the Oceania region have reported fewer instances of MPXV. For example, Israel reported 160 cases, while countries in Southeast Asia and the Middle East such as the UAE, Singapore, India, Saudi Arabia, Thailand, Qatar, Taiwan, Japan, South Korea, and the Philippines reported small numbers of MPXV cases. Only Australia recorded 58 cases of MPXV and a few number of countries in the Oceania reported a limited number of cases. Most MPXV cases reported in Europe and America were detected through local healthcare and sexual health clinics, without any connection to endemic regions in Africa. Despite a lack of prior documentation of MPXV being sexually transmitted, recent reports indicate that the majority of affected individuals are homosexual [57,58]. It was also reported that MPXV virus was detected in the semen of infected patients [59]. On August 16, 2022, the Iranian Ministry of Health announced the discovery of the first human monkeypox case who was a 34-year-old female from Khuzestan province. The diagnosis was confirmed through the examination of skin lesions and subsequent genetic analysis of the virus. The occurrence of the disease in neighboring countries such as Qatar, the UAE, Saudi Arabia, Turkey, Pakistan, and Lebanon, leads to speculation that the virus may have entered Iran from one of these locations. According to the Nextstrain database, the human monkeypox viruses identified in Iran are part of the B.1 lineage, which originated in Europe and has since spread globally [60]. It is widely believed that human monkeypox was brought into Iran from neighboring countries in the southwestern region, but asymptomatic carriers also play a crucial role in facilitating human-to-human transmission of the virus as natural hosts [61].

2.6. Vaccination

Smallpox vaccines have undergone three stages of development. Initially, smallpox vaccinations were produced by propagating them on calf skin and then collecting them from calf lymph. Nevertheless, the utilization of these vaccines is not currently sanctioned for MPV (mass population vaccination) programs. In contrast, the second iteration of smallpox vaccines are produced using advanced and proper techniques, and are propagated in tissue cell cultures, thereby decreasing the likelihood of infection. Furthermore, each of these generations has been demonstrated to potentially pose a significant risk of adverse outcomes due to the presence of replication-competent vaccinia virus [62,63]. Smallpox vaccines third-generations are using the same methods as their second-generation counterparts. However, they offer improved safety as they contain weakened vaccinia viruses that have reduced replication abilities [[62], [63], [64]]. The FDA has approved to use ACAM2000, a second-generation smallpox vaccine, for use as a prophylactic measure following exposure in emergency situations or during smallpox outbreaks [62]. Following animal studies in both the US and Canada, the vaccine MVA-BN (also known as JYNNEOSTM) was granted approval. Clinical trials have demonstrated its high efficacy and safety, making it a suitable option for preventing MPV infections in various populations [63]. LC16 is FDA and Japan approved [64,65]. Vaccination within the first two weeks can prevent severe disease [66]. Research has indicated that prompt administration of the smallpox vaccine is more effective in averting MPV infection [67]. However, there are good vaccines for MPXV right now.

Three orthopoxvirus vaccines are available: ACAM2000, JYNNEOS, and LC16. In 2015, the FDA approved ACAM2000 for use against smallpox and monkeypox in the United States. It was the only vaccine available for monkeypox in the country from 2015 to 2019 [68,73]. ACAM2000 is a second-generation, replication-competent, plaque-purified, weakened vaccinia virus vaccine. It is delivered via the skin using a scarification technique with a bifurcated needle and multiple skin surface inoculations. This vaccine provides its highest protection within 28 days of administration. Booster shots are recommended each 3 years for those exposed to highly virulent orthopoxvirus strains, and every 10 years for those exposed to less virulent strains such as vaccinia virus or cowpox virus [68]. The MVA-BN vaccine is a third generation live attenuated non-replicating Ankara vaccine [69]. The vaccine requires two doses, spaced 28 days apart, and offers protection for two weeks following the second dose. Clinical studies have recorded robust antibody responses after the first dose [70]. Immunological response can be observed two weeks after vaccination. Those infected with highly virulent orthopoxvirus require a booster shot every 2 years, while those exposed to less virulent strains require one every 10 years [71]. The LC16 vaccine is a third-generation vaccine. Developed and authorized in Japan, it later received approval in the United States for smallpox, but has not yet been granted a license for use against monkeypox. This live, weakened vaccine with limited replication was created using cell culture [72,73]. The LC16 vaccine is derived from the Lister strain and has a B5R immunogenic membrane protein deletion. It is delivered via the skin using a bifurcated needle and can be administered to individuals of all ages, such as infants and children, as part of a multi-dose regimen [[73], [74], [75], [76]]. In order to identify the most effective vaccine, it is crucial to evaluate factors such as reactogenicity, safety, and vaccine-related adverse events, particularly for high-risk and vulnerable populations. Currently, various orthopoxvirus vaccines have been developed and are undergoing investigation.

2.7. Treatment

Presently, there is no definitive cure for monkeypox. However, some medications and treatments used for smallpox such as tecovirimat, cidofovir, and immunoglobulin vaccinia (IVG), could potentially be used to treat monkeypox. Tecovirimat has shown specific activity against several orthopoxviruses, including monkeypox. However, it is not widely available at the moment and should be used with caution. Cidofovir is an antiviral that stops the viral DNA polymerase, while tecovirimat stops the release of the virus inside cells and may have therapeutic effects on monkeypox. Despite the potential of these treatments, the primary approach to managing monkeypox is still through supportive and symptomatic therapy [12,22,27,37].

In 2018, a study investigated the use of monoclonal antibodies to prevent severe infection from MPXV. The study used two antibodies, 7D11 and c8A [77]. These monoclonal antibodies are aimed at mature virions (targeted by 7D11) and extracellular virions (targeted by c8A), effectively hindering the virus from further spreading [78]. The study indicated that these antibodies were successful in preventing and reducing the symptoms of MPXV. Out of the three animals treated, two of them lived and were symptom-free, showing that 7D11 was capable of decreasing the amount of virus by up to 90% at dosages above 1250 PFU/ml [77]. Interferon-beta (IFN-β) is another promising drug with potential for use in treating MPXV. IFN-β is approved for treatment in many diseases such as multiple sclerosis (MS) and works by promoting the production of IFN-induced genes. This activation triggers apoptosis of infected cells, enhances the action of macrophages and NK cells, and inhibits synthesis of proteins within the cell. Additionally, these genes increase expression of major histocompatibility complex-1/II which can have benefits against the virus [79].

3. Discussion

In 1970, a 9-month-old child from the Democratic Republic of Congo (formerly Zaire) was identified as the first human case of monkeypox. Prior to recently reported cases, much of the knowledge regarding human monkeypox had come from examinations of outbreaks in Central and West Africa [[80], [81], [82]]. While the clinical characteristics of a vesicular rash can be helpful in identifying a poxvirus infection, such as monkeypox, laboratory testing is needed to confirm the diagnosis. Several laboratory evaluations can be employed to ascertain a diagnosis of monkeypox, such as virus isolation and electron microscopy, polymerase chain reaction (PCR) testing, enzyme-linked immunosorbent assay (ELISA) tests to identify antibodies including IgG and IgM, immunofluorescent antibody assay, and histopathologic analysis. These tests can help confirm the presence of the monkeypox virus and aid in the diagnosis of the infection [83]. In order to effectively combat the spread of viruses, which do not recognize national boundaries, it is essential for the global community to work together to quickly fill in any gaps in our understanding and to control the outbreak. Without treatments or preventative measures readily available, it is crucial to identify cases as soon as possible in order to contain the disease. As is often the case in medical practice, the symptoms of monkeypox can vary widely from person to person [84]. The WHO considers monkeypox to be a re-emerging disease, and it is known to have the potential to be weaponized as biological weapons. This is because it has the potential to spread rapidly in a population that has no immunity to the virus. While monkeypox is not as contagious or as severe as smallpox or even SARS-CoV-2 (which is responsible for COVID-19 pandemic that rapidly spread all over the world), it can still be a serious disease, especially in people with underlying disease. Therefore, it is important to be vigilant in monitoring for any signs of the disease to prevent the future problems.

4. Conclusion

Previously limited to Africa, monkeypox is now a new concern with occasional cases reported in other countries, including the Western Hemisphere. It primarily spreads through human-to-human contact, either through droplets inhalation or contact with the skin sores of infected patient. To prevent its spread, social distancing and contact tracing are crucial. Inside the cytoplasm, the virus replicates and spreads to lymph nodes through a process called primary viremia. Complications from monkeypox infection can include bronchopneumonia, dehydration, respiratory distress, and encephalitis, with the most severe being corneal scarring, which can result in vision loss. In regions with a high concentration of the rash, supportive therapy, including the use of moist occlusive dressings, may be used to minimize the risk of complications. Given the ongoing occurrence of monkeypox cases worldwide, organizations need to focus on understanding its sporadic appearance in western hemisphere and europe, researching for possible treatment ways and examining the long-term effects of the virus to decrease both morbidity and mortality rate in future.

Funding

None.

CRediT authorship contribution statement

Arash Letafati: Writing – review & editing, Investigation, Conceptualization. Tannaz Sakhavarz: Writing – review & editing, Writing – original draft.

Declaration of competing interest

None.