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\def\citeauthor{~Shaik~Shahireen,
              ~Eka~Vipplavi,
              ~Rachamsetty~Kavya,
              ~Manchikalapati~Bhargavi}
\def\citetitle{\textbf{Monkeypox Virus-Disease of Pandemic Potential}}
\def\copyrightstmt{This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial- ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.}
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\begin{document}


\def\RunningAuthor{Shaik Shahireen et al.}
\firstPage{5}
\articleType{Review Article}
\receivedDate{12 Nov 2022}
\acceptedDate{28 Dec 2022}
\revisedDate{27 Dec 2022}
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\journalDoi{ijpib.v8i1.1493}
\copyrightYear{2023}
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\def\journalTitle{International Journal of Pharmacometrics and Integrated Biosciences}

\title{\textbf{Monkeypox Virus-Disease of Pandemic Potential}}
\author{Shaik~Shahireen\textsuperscript{*},  
            Eka~Vipplavi,  
            Rachamsetty~Kavya, 
            Manchikalapati~Bhargavi~\\[5pt]{Department of Pharmacy Practice, QIS College of Pharmacy, Ongole, Prakasam District, JNTUK University, Andhra Pradesh, India}}

\begin{abstract}
The orthopoxvirus genus includes the monkeypox virus (MPXV). The MPXV virus was first discovered in 1958 in research-use laboratory monkeys, and it was later discovered to infect people in Central and West African nations. Humans typically contract the virus from sick animals or contaminated objects. The virus can also spread from person to person through close contact or respiratory droplets.Monkeypox symptoms include fever, headache, muscle aches, and a rash. The clinical presentation of monkeypox can be mild to severe. Depending on the outbreak, human fatality rates can be anywhere from 1-10\%, with immunocompromised people experiencing more severe instances. Although smallpox vaccination can offer some cross-protection, there is presently no specific therapy or vaccine for monkeypox. Because monkeypox looks similarto other rash conditions, diagnosing it can be difficult. The epidemiology, transmission, and pathophysiology of MPXV need to be better understood in order to create effective prevention and control measures. 
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Monkeypox,\newline Orthopoxy,\newline African Virus,\newline MPXV,\newline Outbreaks
\end{keywords}
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\section{Introduction}
Monkeypox virus is a zoonotic virus that causes a human disease known as monkeypox. The virus was first discovered in 1958 when outbreaks of a pox-like disease occurred in monkeys kept for research. Since then, the virus has been identified in several African countries, including Cameroon, Central African Republic, Democratic Republic of the Congo, and Nigeria. Monkeypox is a rare disease that can range from a mild flu-like illness to a severe and potentially fatal illness.

Monkeypox virus belongs to the family Poxviridae, which includes several other viruses such as smallpox virus, cowpox virus, and vaccinia virus. Like other poxviruses, monkeypox virus is large, complex, and enveloped. The virus has a double-stranded DNA genome and replicates in the cytoplasm of infected cells. Monkeypox virus is highly contagious and can be transmitted through direct contact with infected animals, their body fluids or lesions, or through respiratory droplets from infected individuals.

According to the World Health Organization (WHO) \unskip~\cite{1948847:28135988}, monkeypox outbreaks in humans have been reported in Central and West African countries. The disease was first identified in humans in 1970 during an outbreak in the Democratic Republic of the Congo. 

Since then, sporadic outbreaks have occurred in other African countries, and in 2003, the first case of monkeypox was reported outside of Africa, in the United States \unskip~\cite{1948847:28135963}.

While monkeypox is a rare disease, it can cause severe illness, especially in individuals with weakened immune systems. 

There is no specific treatment or vaccine for monkeypox, but supportive care can help alleviate symptoms and prevent complications \unskip~\cite{1948847:28135973}.

\textbf{Epidemiology}

The epidemiology of monkeypox has been studied extensively in Africa, where outbreaks have been reported over the past several decades. According to a study published in PLOS Neglected Tropical Diseases, between 1970 and 2018, there were 3,342 confirmed cases of monkeypox in Africa, with an overall case fatality rate of 11.4\%. The study also found that outbreaks were more common in the rainy season, which may be related to increased contact with infected animals \unskip~\cite{1948847:28135982,1948847:28135966}.

In recent years, there has been an increase in reported cases of monkeypox in Africa. A study published in The Lancet Infectious Diseases found that between 2017 and 2019, there were 573 confirmed cases of monkeypox in Nigeria, including several outbreaks \unskip~\cite{1948847:28135971}. The study also found that the majority of cases occurred in children under the age of 10, and that person-to-person transmission played a significant role in the spread of the virus during outbreaks.

The monkeypox outbreak in 2022, which came after several years of rare incidents outside of Africa, sickened thousands of individuals worldwide (United Kingdom, Singapore, Israel, United States). Before the first outbreak outside of Africa occurred in the United States in 2003, \unskip~\cite{1948847:28135974}  human monkeypox received little attention from the general public. There have been 47 reported cases of monkeypox, all of which were contracted by contact with domestic prairie dogs (37 confirmed cases and 10 suspected cases) (Cynomys spp.). The pets became infected after coming into contact with imported small mammals from Africa, including African rodents, rope squirrels (Funiscuirus spp.), tree squirrels (Heliosciurus spp.), Gambian giant rats (Cricetomys spp.), brushtail porcupines (Atherurus spp.), dormice (Graphiurus spp.), and striped mice (Hybomys s At least three dormice, two rope squirrels, and one Gambian giant rat were discovered to be infected with monkeypox, according to laboratory tests conducted by the CDC utilising virus isolation and PCR amplification \unskip~\cite{1948847:28135961}. 

Multiple cases of monkeypox were discovered in the UK on May 20, 2022. A person with travel connections to Nigeria was identified as having monkeypox on May 6, 2022. Monkeypox cases two more were confirmed by the UK Health Security Agency (UKHSA) in London on May 12. They are unrelated to each other and have never visited the area where the disease is endemic. Four additional cases were confirmed a week later. Unusually, these patients and the previously confirmed instances had no known contact. The West African clade of the monkeypox virus, which has a case fatality rate of only 1\% and is less dangerous than the other known monkeypox variety (CB, Clade I) following infection, was found to be the source of the outbreak by polymerase chain reaction (PCR) analysis of patient swab samples.

After May 2022, numerous cases of monkeypox were confirmed in non-endemic nations all over the world. Monkeypox was classified as a "evolving threat of moderate public health concern" by the WHO on June 23 as a result of this atypical outbreak. Additionally, on July 23, 2022, the WHO declared the monkeypox outbreaks in numerous nations and areas to be a "Public Health Emergency of International Concern" (PHEIC) \unskip~\cite{1948847:28135962}. Guidelines for the prevention and treatment of monkeypox have been released in numerous nations worldwide. A total of 18 deaths were reported in 9 countries as of September 13, 2022, with 57,995 monkeypox virus infections having been documented in more than 100 countries or regions throughout all six WHO regions. In particular, relatively recent news reported that on September 6, monkeypox was confirmed in the first person in Hong Kong. An epidemiological study showed that the patient, who was 30 years old, arrived in Hong Kong from the Philippines on September 5. As a result of the monkeypox outbreak in Hong Kong, the Hong Kong government has activated a readiness and response plan. In addition, this is the first case of monkeypox to be recorded since the four cases in Taiwan Province, China, were confirmed. Notably, on August 4, 2022, the Centers for Disease Control and Prevention (CDC) in the United States deemed monkeypox a public health emergency. The monkeypox epidemic in the United States is extremely serious, as of September 6, monkeypox had since spread to every state, with a total of 20,733 cases.

The first case of monkeypox in the United States for 2022 was discovered on that day. Belgium and Sweden reported their first instances on May 19. Belgian authorities mandated a 21-day quarantine for all instances of monkeypox. Additionally, Belgium became the first nation in the world to mandate self-isolation for cases of monkeypox. A traveller from the Canary Islands was the first case reported in Italy at the same time. Additionally, a possible case was reported by France. Genomic research The virus identified from a case of monkeypox infection in Portugal revealed that the virus likewise belonged to the WA branch of evolution, which is the branch of evolution that is most similar to the virus carried by cases brought into Portugal from Nigeria in 2018 and 2019. On May 20, two people with monkeypox who had just returned from trips to Europe were confirmed in Australia. The initial cases were verified on the same day in France, the Netherlands, and Germany. The initial instances were confirmed the next day in both Switzerland and Israel, and the patient identified by the Israeli Ministry of Health is also the region's first case of monkeypox.

\textbf{Viral Structure}

Over 197,000 base pairs (bp), more than 190 non-overlapping open reading frames (ORFs), and hairpin termini make up the MPXV genome. The highly conserved core coding region is flanked by the changing ends of the genome, which feature inverted terminal repeats. The morphogenesis and replication of the poxvirus are known to need at least 90 ORFs. Variations in the host tropism, immunomodulation, and pathogenicity of the poxvirus are influenced by a number of the other, so-called non-essential ORFs, many of which are now awaiting functional characterisation. MPXV virions are commonly shaped like barrels or ovals and range in size from 280 to 220 nanometers. Mature poxvirus particles have a characteristic dumbbell-shaped nucleoprotein core that contains a substantial double-stranded linear DNA genome. In addition to the virus's DNA-dependent RNA polymerase and associated transcriptional enzymes, MPXV virions also include more than 30 structural and membrane viral proteins \unskip~\cite{1948847:28135961}.

The extracellular enveloped virus (EEV), which is thought to be in responsible of early dispersion, and the intracellular mature virus (IMV), which is released after cell lysis, are both mature forms of a poxvirus particle and both have the ability to mediate infection. The main structural difference between IMV and EEV is the absence of the additional outermost membrane layer in IMVs. Yet, the viral protein incorporation levels in the two virions differ \unskip~\cite{1948847:28135987}.

\textbf{Pathogenesis}

The three stages of monkeypox typically include incubation, prodrome, and the eruptive stage. 

\textbf{Incubation stage}

Monkeypox virus (MPXV) has been found in various wild rodent and shrew species, pigs, African squirrels, and non-human primates. There is no clear evidence indicating which one of these species is the primary animal reservoir for the virus. Human transmission can occur through handling infected animals or eating or preparing bush meat. The largest recorded series of zoonotic MPXV transmissions happened in the US in 2003, when prairie dogs housed with diseased dormice, rope squirrels, and a big Gambian rat imported from Ghana infected 71 people. Unlike the variola virus (VARV), which is exclusive to humans, MPXV can exist naturally in a variety of mammalian species, making containment and control efforts more challenging \unskip~\cite{1948847:28135981}.

The incubation period of monkeypox virus (MPXV) in animals can vary depending on the species and route of infection. In general, the incubation period ranges from 6 to 14 days, although it can be longer in some cases.Experimental studies have been conducted to determine the incubation period of MPXV in various animal models \unskip~\cite{1948847:28135975}. For example, in cynomolgus macaques, the incubation period ranged from 5 to 15 days after intravenous inoculation and 9 to 12 days after intrabronchial inoculation. In African rope squirrels, the incubation period was found to be 8 to 14 days after intranasal inoculation and 7 to 14 days after intradermal inoculation. In addition, a study conducted in prairie dogs found that the incubation period ranged from 6 to 14 days after inoculation with MPXV \unskip~\cite{1948847:28417901}.

\textbf{Prodrome/Transmission stage}

The prodrome stage of monkeypox virus (MPXV) infection is the initial phase of the illness that occurs after an individual is infected with the virus. This stage is characterized by non-specific symptoms that are similar to those of other viral illnesses. These symptoms may be followed by the appearance of a rash, which is a hallmark feature of monkeypox infection. The rash typically appears on the face and then spreads to other parts of the body, including the trunk and limbs. The rash evolves over several stages and eventually forms pustules that crust over and scab.By direct contact with lesions, body fluids, respiratory droplets, and infected items, the zoonotic MPXV virus can spread from person to person. It indicates that handling infected rats is a common way for the disease to spread. Research on macaques that were exposed to aerosolized MPXV showed that the pathogen initially targets the lower airway epithelial cells before going on to the lymph nodes and then spreading throughout the body via monocytic cells. Later MPX lesions might appear in the lymph nodes, thymus, spleen, skin, oral mucosa, gastrointestinal tract, and reproductive system. In vitro studies suggest that the MPXV may infect most mammalian cells \unskip~\cite{1948847:28135965}. 

Some poxviruses require laminin and other widely dispersed glycosaminoglycans, such chondroitin and heparin sulphates, to adhere to cells. A recent genome-wide search for elements promoting MPXV infection also led to the discovery of proteins involved in glycosaminoglycan synthesis. Hence, the most likely mediators of MPX virion attachment are the extracellular matrix, components of the target cell's surface, or external virion proteins. After attachment, poxviruses either directly fuse with the plasma membrane of the host cell at a pH of 7, or they enter the cell by a low pH endosomal route, releasing the viral core into the cytoplasm. For IMV and EEVs to fuse with the cell, a combination of roughly 12 non-glycosylated viral membrane proteins is necessary. The virus's multi-subunit DNA-dependent RNA polymerase initiates the transcription of the virus once it has entered the host cell, and the early, intermediate, and late proteins are then translated on the host ribosomes. Poxvirus DNA synthesis occurs in cytoplasmic structures, often referred to as "factories," which eventually transform from compact DNA-containing structures enveloped in ER membrane to crescent-shaped structures where virion assembly occurs. Although some mature virions (IMV) are transported by microtubules and absorbed by two membranes made in the ER or Golgi, the majority of mature virions (IMV) remain inside the cell. These virions can merge with the cytoplasmic membrane and exit the cell to become EEV, or they can begin actin polymerization, which pushes the particle towards a neighbouring cell on an actin tail.

The prodromal phase, which lasts for one to four days, is marked by a high fever, headache, exhaustion, and frequently, lymphadenopathy, particularly in the cervical and maxillary regions. Monkey pox and chicken pox can be distinguished by lymphadenopathy. Skin lesions develop in a centrifugal pattern and go through many stages during the eruptive phase, which lasts for 14 to 28 days: macules, papules, vesicles, and pustules. The lesions show umbilication and are solid and well-defined. Lesions form crusts that desquamate, leaving behind hypopigmented and then hyperpigmented patches. The face, torso, arms, and legs are the main areas where a patient may have a few to several thousand lesions.

\textbf{Eruption Stage}

The eruption stage of monkeypox virus (MPXV) infection is characterized by the appearance of a rash that begins on the face and then spreads to other parts of the body, including the trunk and limbs. The rash evolves over several stages and eventually forms pustules that crust over and scab.The rash usually appears about 1-3 days after the onset of fever and other prodromal symptoms, although in some cases, it may take up to 14 days to appear. The rash usually starts as flat, red spots that become raised and fluid-filled over the next few days. The spots may then develop into small pustules, which are elevated, dome-shaped lesions filled with pus. The pustules are typically 2-5 mm in diameter and may be surrounded by an area of redness.

Over the next several days, the pustules will become larger and more numerous, and may be accompanied by other symptoms such as fever, headache, muscle aches, and fatigue. The pustules can become very large and painful, and may be associated with severe itching. In severe cases, the pustules can become confluent, meaning they merge together to form large areas of infected skin.After about 10-14 days, the pustules will begin to dry out and form crusts. The crusts will eventually fall off, leaving behind scabs that may take several weeks to heal completely. The scabs may leave scars, particularly if they have been scratched or picked at.It is important to note that the eruption stage of MPXV infection can be associated with a range of other symptoms, and can be mistaken for other diseases that cause a similar rash, such as chickenpox or smallpox. Therefore, laboratory testing is necessary to confirm a diagnosis of monkeypox and to differentiate it from other diseases.

\textbf{Diagnosis}

For identifying the existence of an orthopoxvirus infection, diagnostic tests are essential. In the table below, the diagnostic procedures that can be used to determine if clinical specimens contain monkeypox or Orthopoxvirus are mentioned. These tests work best when combined with clinical and epidemiological information, including a patient's vaccination record. Due to the damaged cold chain and limited resources for sample collection and storage, lesion exudate on a swab or crust specimens continue to be some of the best and least intrusive acute patient specimens. It is crucial to remember that viral DNA present in lesion material is stable for a long time if kept in a somewhat dark, chilly environment when cold chain is not easily available. Although they still have value, traditional diagnostics like viral isolation from a clinical sample, electron microscopy, and immunohistochemistry need sophisticated lab equipment and highly trained personnel. If monkeypox or orthopoxvirus is present in a sample of a lesion, real-time polymerase chain reaction (PCR) examination of specimens can be performed to identify the presence of the virus \unskip~\cite{1948847:28135989}. These assays are extremely capable of detecting viral DNA. Real-time PCR is now most successful in big laboratories; hence, its use as a real-time diagnosis in rural areas with little resources is still restricted. Due to developments in technology, real-time PCR for diagnostic reasons may become increasingly applicable outside of big facilities. To find the cause of cases revealed after the fact, antibody-based diagnostics are needed. 

Orthopoxvirus cross-reactivity makes anti-Orthopoxvirus immunological tests useful in situations when the specific virus causing illness has previously been identified. Anti-orthopoxvirus immunoglobulin G (IgG) alone will not provide a clear diagnosis for those persons who have ever been exposed to an orthopoxvirus, including through vaccination. Serological tests that measure anti-Orthopoxvirus immunoglobulin M (IgM) are more suitable and can detect current diseases, even those in patients who have had immunisations in the past \unskip~\cite{1948847:28135978}. Field deployable point-of-care tests are excellent, however there haven't been many developments in this space. A recent trial of the TetracoreOrthopoxBioThreat Alert achieved positive outcomes using lesion samples from acute orthopoxvirus infections. This test consistently recognised the vaccinia and monkeypox viruses in preparations with 107 plaque-forming units/mL, and 5 out of 6 clinical specimens that were analysed were accurately identified \unskip~\cite{1948847:28135979}. As this assay may be used in monkeypox-endemic areas for Orthopoxvirus confirmation by proxy despite not being particularly for monkeypox virus, it will be vital to evaluate it in endemic situations. As patients with monkeypox virus typically seek diagnosis and care in remote clinics or hospitals without electricity, there is a need for the development of tests that can be carried out in incredibly primitive settings with limited worker training.

\textbf{Treatment}

Those who are at risk may benefit from early post-exposure immunisation since MPX has a lengthy incubation period (5 to 21 days). After post-exposure immunisation, challenge experiments on prairie dogs \unskip~\cite{1948847:28135977}  revealed a decrease in the severity of MPX illness, but studies on non-human primates were unable to convincingly demonstrate a benefit \unskip~\cite{1948847:28135984}. These inconsistencies may have been caused by the virus's prolonged incubation time in the intranasal prairie dog infection model, which more closely reflects the course of a typical human infection and allows time for the body to mount an immune response \unskip~\cite{1948847:28135968}. Passive immunisation with immune sera or vaccinia immune globulin has been given to close contacts of smallpox cases and immunocompromised people with progressive vaccinia \unskip~\cite{1948847:28135967}. Vaccinia immune globulin intravenous (VIGIV), despite there is no clinical trial data to support its efficacy against MPX, is safe and may be used to treat individuals who are at risk. Only Tecovirimat has FDA and EMA approval as a treatment for human orthopoxvirus infection (ST-246). While it is rarely used, it was in 2021 that patients with severe MPX were treated with it; these patients later made a full recovery \unskip~\cite{1948847:28135986}. Tecoviromat suppresses the production of enveloped virions and their dissemination by interfering with the membrane trafficking of the p37 viral envelope protein \unskip~\cite{1948847:28135976}. It was shown in the monkey model that this drug may prevent MPX mortality without having any negative side effects. Moreover, research has shown that the drug cidofovir, which has a licence to treat cytomegalovirus (CMV) retinitis in AIDS patients, is effective against lethal MPXV infection in macaques \unskip~\cite{1948847:28135969}. Nevertheless, it is uncertain if cidofovir works against MPX in patients. Because there is so little data on how effectively the authorised drugs perform against MPX in humans, their usage will likely continue to be limited to treating severe instances.

\textbf{Vaccination}

Smallpox immunisation is regarded as one of the ways to reduce MPXV outbreaks due to the antigenic similarities between VACV and MPXV. Data gathered between 1980 and 1984 reveal a substantial difference between the attack rate for vaccinees (0.9\%) and the total attack rate for contacts of unvaccinated MPX case contacts (7.2\%). Between the 1980s and 2007, there were approximately 20 times as many recorded human MPX cases in the DRC, and the median age of MPX patients increased{\textemdash}likely as a result of the discontinued smallpox immunisation. In population studies conducted in the DRC in the 1980s, it was discovered that immunisation provided 85\% protection against MPX \unskip~\cite{1948847:28135970}. Vaccinated people have a much lower risk of MPX even 25 years after receiving the vaccine, according to data gathered in the DRC between 2005 and 2007. Similar findings were made after the 2003 US MPXV outbreak, when three asymptomatic cases were found in people who hadn't yet developed immunity. Smallpox vaccines in the past included live, unattenuated VACV strains. Due to its high immunogenicity, this type of vaccination is quite successful, although immunocompromised persons may experience negative side effects. Additionally, replication-competent VACV strains have been discovered to spread to the close contacts of vaccine recipients in a small number of cases \unskip~\cite{1948847:28135964}. There are now two smallpox vaccinations that have been licenced for use in humans in the US and Europe. The immunocompromised cannot receive single-dose ACAM2000 or Aventis Pasteur Smallpox Vaccine (APSV) because they contain replication-competent live vaccinia virus. The most recent two-dose MVA-BN vaccine (brand names JYNNEOS, IMVAMUNE, and IMVANEX) contains a replication-deficient virus and is safe for those with immune system compromises \unskip~\cite{1948847:28135985}. MVA and MVA-BN immunisation was proven to offer complete protection against severe MPX in non-human primates, while it is still unclear if replication-competent and non-replicating vaccines are equally beneficial in people. 

The US Food and Drug Administration (FDA) has only presently authorised JYNNEOS as a vaccination to prevent monkeypox. The JYNNEOS postexposure vaccine is also available to patients who have had intimate contact with someone who has the monkeypox virus. The CDC recommends immunisation after 4 days of exposure to prevent disease or up to 14 days after exposure to minimise the severity of illness. 8 There are now more than 36 000 doses of the JYNNEOS vaccine in the US Strategic National Stock. Although the CDC has recommended that close relatives of monkeypox patients receive the JYNNEOS vaccination, this vaccine is currently difficult to obtain.

A highly attenuated smallpox vaccine, LC16m8, has also been created and given Japanese licencing. It has an enhanced safety profile. More research is required to determine how long the protection lasts, especially in vulnerable populations and the immunocompromised. The data now available suggest that smallpox immunisation may provide long-term protection from MPX. Close contacts of MPX cases were offered pre- and post-exposure vaccination in the US and UK during the 2003, 2018, and 2019 outbreaks \unskip~\cite{1948847:28135980}  as they were the first nations to explore a ring-vaccination method. The number of nations that have agreed to offer immunisation to those who have been exposed to MPXV or are at risk of contracting it has increased over the past month, although the uptake rate is unknown. Despite this, in June 2022, the UK Health Security Agency and the New York City Department of Health and Mental Hygiene began providing the vaccine to gay and bisexual males at higher risk of exposure to help contain the recent viral outbreak \unskip~\cite{1948847:28135983}. Since then, many other areas with a high rate of new cases have started acting similarly, even though there are currently few vaccines available. The European Health Emergency Preparedness and Response Authority (HERA), in response to the ongoing MPXV outbreak, requested 110,000 doses of the non-replicating Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) vaccine in June 2022.
    
\section{DISCUSSION}
Concerns about the potential damage this zoonotic virus presents to public health throughout the world are raised by the rapid increase of MPX infections in non-endemic places. Between 4 May and 12 July 2022, almost 10,000 new non-endemic MPX cases were reported globally. This number is certainly understated since MPXV diagnostics are sometimes difficult to get. The constant risk assessment of the MPX danger level and the containment and management of the pandemic will both depend heavily on disease surveillance. Host factors like international travel and rising poxvirus susceptibility aided in the pathogen's global spread, though more research is urgently needed to ascertain whether the MPXV strains currently in circulation differ from earlier isolates in their ability to transmit and/or their pathogenicity. Due to the termination of smallpox vaccinations, which offered cross-protection against MPX, immunity has decreased, which has been linked to an increase in MPX cases. 

Unvaccinated children made up the majority of the recorded cases of endemic MPX in the 1970s and 1980s. The median age of MPX patients did, however, increase over time as new generations born after smallpox eradication grew more vulnerable \unskip~\cite{1948847:28135972}. Despite the fact that smallpox vaccinations effectively protect against MPX, widespread immunisation is not essential given the scope of the present outbreak. Instead, giving the vaccine to particular people, such MSM at risk of exposure, medical experts, and close relatives of MPX victims, is a potential strategy for containing the MPXV spread. Moreover, there is optimism that pharmaceutical and immunoglobulin-based therapeutic strategies can help prevent the worst sickness consequences. Given the low MPXV mutation rates and durable vaccine-induced immunity, an effective escape from adaptive immunological responses is unlikely but not absolutely impossible. Thus, there is an urgent need for more study on this reemerging virus, particularly on the cases linked to the epidemic in 2022. In the current non-endemic epidemic, a new high-risk category has been identified: men who have sex with men (MSM) who have recently had contact with new or multiple sexual partners. This demonstrates how MPXV is distributed by close physical contact. The fact that this virus may infect and disseminate to persons of any sex, age, or orientation is more essential than anything else, as shown by both the previous and more recent MPXV epidemics. The hypothesis that the clinical consequences of the current epidemic are less severe than those found in endemic areas is supported by the absence of MPX mortality in non-endemic locations. A relatively tiny proportion of the current MPX patient group consists of members of the most susceptible demographics, such as babies, expecting women, or people with compromised immune systems. 

Hence, the health risks of a widespread MPXV epidemic are probably larger than what has been observed in recent weeks. Due to its wide species tropism, MPXV has the potential of establishing animal reservoirs in regions where it is not endemic, which might sustain upcoming outbreaks. Monitoring changes in the demography of afflicted individuals and potential spill over events to wildlife or domesticated animals is crucial for risk assessment and making informed decisions about extending or adopting additional safety measures against MPX. The threat posed by MPX is still there, but it may be reduced by enhancing MPX surveillance and enhancing access to vaccinations and antiviral drugs.
    
\section{CONCLUSION}
Human monkeypox has the capacity to spread via zoonotic reservoirs, as evidenced by the outbreak. Concerns about the virus spreading into regions where monkeypox does not exist or about people migrating to more heavily wooded areas where they are more likely to come into contact with wildlife and develop other zoonoses are raised. In order to better comprehend the variety of elements involved in disease transmission and dissemination, greater examination, investigation, and research are necessary in light of the observed increase in the frequency of human disease. There are still many unsolved concerns regarding the virus, animal reservoirs, and human disease; advancements in our knowledge of this significant zoonosis can assist improve preventative methods and lessen the severity of human illness.
    
\section{ACKNOWLEDGEMENT}
The authors thank every who supported and contributed for the work.

\textbf{Financial Support}

There is no funding support for this work.

\textbf{Conflict of Interest}

The authors declare that there is no conflict of interest in this work.
    

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