• Monkeypox virus (MPXV) is an enveloped , double-stranded Virus that is part of the Genus Orthopoxvirus within the family of Poxviridae.
• The Monkeypox virus (MPXV) was first discovered and reported by the Statens Serum Institut (Copenhagen, Denmark) in 1958 , after two outbreaks of the disease were discovered in cynomolgus macaques.
• The first human case of monkeypox was recorded in August 1970 from the remote town of Bokenda in the province of the equatorial of Democratic Republic of the Congo (DRC).
• Monkeypox was thought to be a rare sporadic disease that had a very limited ability to spread among people at the time (WHO 1984). However the number of cases reported and their geographic range has grown since the end of smallpox vaccinations and the illness can be life-threatening in DRC as well as other countries in West as well as Central Africa
• Monkeypox is believed to be an endemic disease in West Africa and Central Africa.
• In 2003 there was a mongoose pox outbreak that was not in Africa and was observed within the United States of America. Recently, cases of monkeypox have been reported in a variety of non-endemic nations, bringing awareness.
• The genome of the monkeypox virus 196,858 bp comprises 200 open reading frames that contain >60 amino acid residues.

What is monkeypox virus?

• The vaccines that were used in the program to eradicate smallpox also offered protection against the monkeypox. Newer vaccines have been created of which one is accepted for the prevention of monkeypox.
• Monkeypox is caused through monkeypox virus, which is a member of the Orthopoxvirus genus within the family of Poxviridae.
• Monkeypox can be a self-limiting illness that can last between 2 and 4 weeks. The severity of the cases is variable. In recent years the rate of fatality in cases was around 3-6%..
• Monkeypox spreads to humans via contact with an infected animal or person or through contact with materials infected with the virus.
• Monkeypox virus can be transmitted from one person to the next through close contact with body fluids, lesions drops from respiratory tracts, as well as items like bedding.
• Monkeypox is an infectious zoonotic disease that is prevalent in tropical rainforests in west and central Africa and occasionally spreads to other parts of the world.
• An antiviral drug developed for treatment of smallpox was also granted a license for the treatment of monkeypox.
• The symptoms of monkeypox is similar to that of smallpox. It is an orthopoxvirus disease that was declared eliminated worldwide in the year 1980. Monkeypox is not as contagious as smallpox, and is less likely to cause severe symptoms.
• Monkeypox is typically seen as a clinical manifestation with swelling, fever and rash. lymph nodes, and can result in a myriad of medical issues.

Classification of Monkeypox Virus

• MPXV is an genus member. Orthopoxvirus (OPV) as well as the family Poxviridae.
• MPXV is among the five OPV species that are pathogenic for humans, along with variola virus, which is the causal agent for smallpox currently eradicated in the natural world, camelpox virus, cowpox virus as well as vaccinia virus.
• Poxviruses are prevalent in vertebrates as well as invertebrates, and can cause a range of ailments of veterinary as well as medical significance.
• Family Poxviridae is subdivided into subfamilies Chordopoxvirinae which has viruses that are able to infect vertebrates, and the subfamily Entomopoxvirinae that infects insects.
• This subfamily Chordopoxvirinae has been divided in 11 genera. among that is OPV.
• Every OPV species, except for variola virus, which is an exclusive human pathogen, possess animals as reservoirs. They are classified as Zooonotic pathogens.

Morphology of Monkeypox Virus/Structure of Monkeypox Virus

• Monkeypox virus, in conjunction with other poxviruses is thought to be one of the biggest and most complicated viruses.
• They’re brick-like-shaped particles that range between 220 nm and 350 nm in length, and 140 nm up to 260 millimeters in width. Therefore MPXV’s size is sufficient to be detected by a light microscope, and has its ultrastructure being resolved by electron microscopy. However, greater magnification by electron microscopes is needed for the resolution of the ultrastructure.
• The orthopox virion is composed of four main elements: the core, the lateral bodies, the outer membrane and the lipoprotein outer envelope.
• The central core is home to double-stranded DNA of the virus (dsDNA) and fibrils that make up the core and is enclosed by a tight-knit rod-shaped structure called the palisade layer.
• Central core, the palisade layer and the lateral bodies are surrounded by an outer membrane, which is made up of a variety of tubules on the surface.
• Virions that are released spontaneously usually contain the lipoprotein outer envelope and virions that are released through cell disruption do not have this envelope.
• A mature virion is composed of at minimum 80 viral proteins.

Genome Structure of Monkeypox Virus

• The monkeypox genome comprises a massive (197 Kbp) monolinear molecule made of DNA, which is among the biggest in the world of viral genomes.
• The genome at each end has identical, but different terminal reads, with a total size of 6 kbp and an array of short tandem repeats as well as hairpin loops at the terminal.
• The genome consists of approximately 180 non-overlapping open reading frames (>180 Bp long) that contain at least 60 amino acid residues. Four of these are located in the inverted terminal repeat.
• The content of cytosine and guanine in MPXV DNA is very low, approximately 31.1 percent.
• There are two distinct genetic clans of MPXV have been identified, including those belonging to the West African (WA) and the Central African (CA) clade. The sequencing of the entire genome of several OpVs has revealed an extremely high level of homology between genes in the central region, as well as large variation in genes on the terminal ends of the genome.
• Conserved OPV genes are involved in vital viral activities like virion assembly and replication, and also in the various OPV terminus reads most likely to be a factor in the viability of various OPVs.
• Numerous terminal genes aid in the evasion of the immune system by hindering the presentation of signals, signaling, and recognition of antigens as well as the process of apoptosis.

Genome Structure

• The genome as a whole comprises 196,858 Bp, with the central genomic region comprising 101,476 Bp.
• Both terminal variables come to an end (right end is longer than the left) include the terminal’s inverted repetition (ITR) with around 80 bp of hairpin loop 70 bp shorter 54-bp tandem repetitions and two unique ITR sequences, the NR 1 and NR 2 as well as the coding region.

Replication Cycle of Monkeypox Virus

The cycle of replication for poxviruses is different from that of other DNA viruses, is carried out in the cytoplasm within the cell that hosts them. Poxviruses infiltrate cells through an elaborate process that includes attachment, hemifusion and the entry of the core within the plasma membrane, or following the process of endocytosis.

1. The specific mechanism employed by the poxviruses in order to enter cells is determined by its infective form, which is a mature virion (MV) with one outer membrane, or extracellular enveloped virion (EV) that has an additional membrane that has distinct protein composition.
2. In the EV form the membrane that is specifically EV-specific is eliminated, leaving the underlying membrane, which is fused to the cell.
3. Although MV is more common, EV is specialized for cell-to-cell transfer mainly through its long, mobile projections, which are created through the polymerization of actin that binds to the cell’s surface.
4. The mature virion is subjected to the first removal of its coating during its entrance, and after it is in the cytoplasm of the cell, viruses release prepackaged enzymes and other enzymatic components that weaken cell defenses and trigger expression of the first genes.
5. Then, it follows a creation of messenger RNA early (mRNA) via the viral DNA-dependent polymerase.
6. The early mRNA translation process facilitates the uncoating process that follows DNA replication and creation of transcription factors intermediate to the original.
7. Then the intermediate mRNA is then transcribed and translated to trigger its expression in late mRNAs, and its transformation into non-structural proteins and structural protein (enzymes as well as early transcription factors).
8. The translated proteins are put together along with DNA concatemers formed at the beginning stages of replication. They then get into immature virions which grow into intracellular mature viruses (IMVs).
9. IMVs are not covered by an outer membrane and become only infectious when released as a result of disruption of cells.
10. IMV particles that did not get encased in the cytoplasmic protein matrix are transformed into intracellular enveloped virions (IEVs) through the acquisition of another membrane.
11. These cells migrate to the cell membrane through the use of microtubules. They then fuse with the cell membrane, forming cell-associated viruses (CEVs) that trigger polymerization of actin as well as the creation of filaments that aid in the process of allowing CEVs to escape the cell.
12. The CEVs that have been removed from the cell are known as extracellular enveloped viruses (EEVs).
13. Both extracellular and intracellular viral toxins play a significant part in the process of pathogenesis.
14. The intracellular viral virions (IMV as well as IEV) as well as CEVs are the primary cause of spreading the disease from one cell cell and EEVs are essential for the spreading of virus inside an infected organism.

Clinical Profile of Monkeypox Virus

Incubation Period

• Most people with MPXV are symptomatic, however the subclinical (asymptomatic) infection may be seen.
• The information available is limited regarding the time of incubation of MPXV in humans, however recent research suggests 5-13 days. The longest time for incubation was approximately 17 days.
• However, an incubation time of 21 days is assumed to provide extra precautions.
• The duration of the incubation process and the severity of disease, as well as the presentation as well as duration of the illness can be affected by the method of transmission. For instance, infection through bites could cause a shorter incubation duration, the absence of a distinct febrile stage and more severe disease as opposed to non-invasive exposures.

Monkeypox virus symptoms

The appearance of the disease in monkeypox closely resembles smallpox, despite being more mild clinically. The primary difference between monkeypox from smallpox lies in the appearance of lymph node swelling.

• The human monkeypox virus can be classified into two phases, the prodrome as well as the rash.
• The prodrome is characterized by symptoms like headache, fever, chills or sweats. It can also be characterized by sore throat pain in the muscles, lack of energy and lymphadenopathy.
• The rash is usually seen 3 to 7 days after the onset of fever or lymphadenopathy. It is characterised by a small to a couple of thousand lesions.
• The lesions show up all at once and grow at around the same pace. The lesions develop from papules to macules, pustules, vesicles and then to crusts. The distribution of the lesions is mostly peripheral however they can spread across the entire body when there is a serious disease.
• Based in the degree of disease The time frame is between two and three weeks for the lesions dry and then desquamate. People who are vaccinated against smallpox using the vaccine against vaccinia have significantly fewer lesions than those who are not vaccinated.
• Patients frequently experience symptoms of gastrointestinal distress like nausea diarrhoea, vomiting, diarrhea and loss of appetite.
• Lesions of the alimentary tract and oral cavity are often apparent.
• The rash’s skin irritation may lead to a secondary bacterial infections (common) and dehydration.
• Ocular infections involving MPXV or secondary bacterial infection may also occur , and usually leave the eye of the patient swollen, red, and sensitive to light and may result in loss of vision.
• The respiratory tract can be affected. Patients may be diagnosed with coughing, trouble breathing, or bronchopneumonia.
• Other issues include encephalitis and sepsis.

Pathophysiology

• In the event of an entry via any source (oropharynx oropharynx, nasopharynx or intradermal) The monkeypox virus multiplies at the inoculation site and it spreads to lymph nodes in the local area.
• Then after that, a first viremia leads to the spread of viral infection and the seeding of various organs.
• This is known as the incubation time which typically lasts between 7 and 14 days, with a maximum limit of 21 days.
• The onset of symptoms is associated with a secondary viremia, which can cause up to 2 days of symptoms that are prodromal like swelling and fever prior to the first signs of lesions show. Patients with a virus may transmit the disease during this time.
• The lesions begin in the oropharynx and then show up in the face. Serum antibodies can be detected when lesions first appear.
• The progression of the Rash is explained more in depth within this section. History section as well as in the Physical section.

Host Specie

• Monkeypox is a zoonotic illness in which the reservoir that keeps this virus isn’t identified. Numerous animal species have been identified as being animals who are at risk of contracting the virus, with the most common being rodents as well as non-human primates.
• Non-human primates are generally regarded as hosts that are incidental and have no role that is crucial to the development of the virus in the wild because of the small OPV seroprevalence among these animals.
• Squirrels, giant pouched rats (Cricetomys spp. ) as well as African dormouse (Graphiurus spp.) as well as other rodents from the forest are thought as the likely reservoir host species, based on evidence from various labs and fields.
• The virus has been isolated from two wild animals including a rope squirrel from the DRC and a mangabey that was sooty located in Ivory Coast.

Transmission of Monkeypox Virus

Monkeypox is spread in many ways.

Person to Person Transmission of Monkeypox Virus

• Monkeypox is spread via close, personal typically skin-to-skin contact. This includes:
  • Contact with the rash of monkeypox and scabs or body fluids from someone who has monkeypox.
  • Fabrics, objects (clothing bedding, towels or towels) or surfaces that have been touched by a person suffering from monkeypox.
  • The contact with the respiratory secretions.
• Direct contact may occur through intimate contact, which includes:
  • Oral or vaginal sexual activity, or touching the sexual organs (penis labia, testicles as well as vagina) or the anus (butthole) of the person who has monkeypox.
  • Massage, hugging, and kissing.
  • Face-to-face interaction that lasts for long periods.
  • Contacting objects and fabrics during sex which were used by a person suffering from monkeypox but aren’t disinfected, like towels, bedding as well as fetish gear and sexually explicit toys.
• A woman who is pregnant can transmit this virus onto their baby via the placenta.

Animal-to-human (zoonotic) transmission 

• Human-to-animal (zoonotic) transmission can result by direct contact with body fluids, blood, or mucosal or cutaneous lesions in animals that are infected.
• In Africa the evidence of the virus monkeypox is found in a wide variety of species of animals, including rope squirrels, tree squirrels, Gambian pouched rodents, dormice, various species of monkeys and many more. The source of monkeypox hasn’t yet been discovered however rodents are the most likely candidates.
• Consuming uncooked meat or other animal products from affected animals could be a risk aspect.
• People who live near or in forested areas could be exposed or low-level exposure to diseased animals.

How to prevent monkeypox?

Following the steps for prevention and getting vaccinated if have had exposure to monkeypox, or are at a higher chance of exposure to monkeypox could help ensure your safety and that of your neighbors.

1. Protect Yourself

• Avoid contact with skin with those who have an rash that resembles monkeypox. Do not contact the rash or scabs of a person who has monkeypox. Don’t kiss, hug or cuddle with anyone who has monkeypox.
• Avoid contact with materials and objects that a person who has monkeypox has touched: Avoid sharing the eating utensils or cups you use to eat with someone who has monkeypox. Avoid touching or handling the towels, bedding, or clothes of someone who has monkeypox.
• Clean your hands frequently Clean your hands frequently with soap and water . You can also apply an alcohol-based hand cleanser prior to eating or touching your face after using the bathroom.

2. Vaccines

• The most effective vaccine to guard against the virus monkeypox is JYNNEOS It is a two-dose vaccination. The vaccine takes about 14 days following receiving the second dose of JYNNEOS to ensure that it has the protection of its immune system to be at its highest.
• The ACAM2000 vaccine is an option to replace JYNNEOS. ACAM2000 is a one-dose vaccine that is required for four weeks after the vaccination for its immune defense to be at its highest.
• But, it does have the potential for having more adverse reactions and side effects than JYNNEOS. It’s not recommended for individuals with compromised immune systems as well as other ailments.
• It is recommended that people take steps to limit the risk of contracting monkeypox up to the point that the immune protection provided by vaccines has reached its peak.
• Ask your physician to determine if you need to be vaccinated against monkeypox and also if you should get ACAM2000 as opposed to JYNNEOS.

4. Safer Sex

• You should take a break from any activities that could increase your the risk of contracting monkeypox until you reach two weeks following your second dose. This will significantly decrease the chance of contracting the virus.
• Limit your number of sexual partners to limit your risk of being exposed.
• Back rooms saunas, back rooms or even public and private sexual gatherings that have intimate, and often intimate sexual encounters with several partners is common, are more likely to transmit monkeypox.
• Condoms (latex or polyurethane) could help protect the anus (butthole) or penis, mouth and vagina against exposure to the virus monkeypox. But, condoms alone will not be able to prevent all exposures to monkeypox as the rash can also affect other areas of the body.
• Gloves (latex polyurethane, polyurethane or Nitrile) can also limit the risk of being exposed by inserting hands or fingers inside the vagina and anus. The gloves should cover all exposed skin and then removed with care to avoid contact with the outside of the.
• Do not kiss or exchange Spit, as monkeypox could be transmitted this way.
• The two of you can muddle around at a distance without touching and also without touching any bumps.
• You can have virtual sex without personal contact.
• You may want to consider having sex with clothing over or covering areas where there is a rash, and limiting the amount of skin-to-skin contact is. Latex or leather gear also creates a barrier against skin-to-skin contact. Be sure to change or wash your the gear and clothes between partners, and after each use.
• It is important to be aware that monkeypox may be spread via respiratory secretions if you are in close eye-to-eye contact.
• Be sure that you wash your hands after using sexually explicit toys, fetish equipment and all textiles (bedding towels, clothing, bedding) after you’ve had sexual contact. Learn more about how to control infection.

5. Avoid Social Gatherings

• Events, festivals and concert events where the attendees are dressed in full and are unlikely to have contact with skin are more secure. However, the attendees must be wary of actions (like kissing) which could spread the virus.
• A party, rave, or club with no clothing or when there is intimate, personal, and often skin-to skin contact is not without risk. Avoid any rash you spot on someone else and think about limiting contact with skin.
• Closed-off spaces, such as saunas, back rooms, sexual clubs, or the public and private sex clubs in which intimate, and often secret sexual contact between more than one partner, could have a greater chance of spreading monkeypox.

6. Reduce Monkeypox Transmission in Congregate Living Settings

If a case of monkeypox has been discovered in a living space that is congregate Consider the following actions:

• Engage with volunteers, staff and residents. Give clear and concise information to residents, volunteers, and staff regarding the prevention of monkeypox, including the possibility of transmission through frequent, prolonged physical contact, as well as sexual contact.
• Respond to incidents Examine and test medically personnel volunteers, residents, or others who are suspected of having monkeypox. Contact your state local, tribal, and territorial health departments prior to stopping isolation.Ensure that patients with monkeypox are wearing a comfortable disposable mask for their mouths and noses, and cover any lesions on their skin with long sleeves and long pants and bandages or a gown or sheet when they are required be removed from the isolated location or if isolation facilities aren’t available.Isolate personnel or volunteers with monkeypox out of areas of congregation until they are completely recovered. Reduce the number of employees who are admitted to isolation zones to those who are crucial to the isolation zone’s operations.
• Determine if someone has been exposed to the monkeypox virus: Facilities should collaborate with their tribal, state local, territorial, or health department to determine and examine the health of any personnel members, volunteers, or residents who could have been in an intimate relationship with someone with monkeypox.
• Provide access to handwashing facilities soap and water, or hand sanitizer containing at minimum 60% alcohol must be readily available and free for all employees, volunteers and residents. Anyone who gets in contact with lesions, clothes, linens, or other surfaces that might be in contact with them must wash their hands promptly.
• Clean and disinfect the areas in which people who have monkeypox were spending time Avoid activities that can cause the spread of dried material by causing lesions (e.g. the use of fans or dry dusting sweeps, vacuuming, etc.) in these areas.
• Use proper PPE (PPE) for employees or volunteers as well as residents Employers are responsible to ensure that employees are safe from exposure to Monkeypox virus and ensure that employees aren’t exposed to dangerous concentrations of chemicals used in the cleaning or disinfection.

7. Disinfecting Home and Other Non-Healthcare Settings

• Monkeypox sufferers who reside in isolation at home must clean and disinfect the areas they live in, which includes frequently used surfaces and objects, to reduce the risk of contamination in households.
• Make sure you wash your hands afterwards with an alcohol-based rub (ABHR) which contains at minimum 60% alcohol as well as soap or water in the event that ABHR is not available.
• Monkeypox sufferers who are isolated in a household with other people who do not have the virus must follow the isolation and infection control guidelines as well as any shared areas such as appliances, furniture, or other items must be cleaned immediately after usage.
• If the cleaning and disinfection process is performed by someone different from the one with monkeypox, the person must at a minimum disposable medical glove and a respirator with a good fit mask.
• If the cleaning and disinfection process is performed by someone different from the one with monkeypox, the person must wearat least disposable medical glove, and a respirator with a good fit mask.
• Standard clothes that cover the skin must be worn and washed immediately following the recommendations below.
• Hand hygiene must be done with an ABHR as well as soap and water in the event that there is no ABHR available.
• Concentrate on cleaning surfaces and items that came in direct contact with skin of the patient with monkeypox. Often, this is with the patient with monkeypox in the isolation. If you are unsure, clean.
• Do not dry or dry sweep, as this can cause the spread of infectious particles.
• Cleaning methods that are wet are preferred like disinfectant wipes sprays and mopping.
• Vacuuming is safe when using a vacuum that has an air filter with high efficiency. If it isn’t available, make sure that the person who is vacuuming is wearing a suitable respirator or mask.
• Disinfect and clean your home in the order listed below:
  • General Waste containment
    • Take and store in a bag that is sealed any polluted waste, including paper towels, bandages, food packaging and other general waste items.
  • Laundry
    • Take the linens and clothing that are contaminated prior to ensuring that everything that is in the space is cleaned. Be careful not to shake the linens, as it could transmit infective particles.
  • The hard surfaces of household items and the furniture
  • Furniture with upholstery and other soft furnishings
  • Carpet and flooring
  • Waste disposal

8. Pets in the Home

• Have your pet tested in the event that they’ve had close contact with someone who has confirmed or probable monkeypox and have the rash is new or has other signs of clinical illness.
• Keep the pet that is sick or animal from all other animals and avoid contact with other animals within the 21st day following being sick or until completely recovered.
• Make sure to wash your hands regularly and wear Personal Protective Equipment (PPE) when handling as well as cleaning up after animals that are sick. PPE involves wearing gloves, wearing protective eyewear (safety glassesor goggles or a face shield) as well as a properly fitted respirator or mask (ideally an NIOSH-approved disposable mask with a filtering nosepiece) and wearing disposable gowns.
• Contact your local public health department for recommendations on garbage disposal.
• Bedding enclosures, food dishes and other things that come into direct contact with infected animals should be disinfected after the process of disinfecting the home and other non-healthcare settings.
• Clean bedding and laundry (including disposal rodent bedding) shouldn’t be handled or shaken in a way that could release infectious particles.

Treatment of Monkeypox Virus

• There is no treatment approved for MPXV infections. Thus, treatment is one-time and is supportive.
• There are several antivirals that have been studied and show effectiveness against MPXV in vitro as well as animal models. They include brincidofovir, cidofovir and tecovirimat. However, none of them was tested in a clinical study.
• Tecovirimat has been approved by the US Food and Drug Administration for treatment of smallpox.
• The mechanism of the action of cidofovir is the inhibiting of virus DNA polymerase.
• Similar to brincidofovir. It is an improved cidofovir which is not afflicted with nephrotoxicity, and is available orally. Instead it targets a specific viral substance that prevents it from releasing intracellular viruses within the cell.

Diagnosis of Monkeypox Virus

Doctors diagnose monkeypox using several methods:

• Medical background. That includes the travel experience that can aid your doctor in determining the risk you face.
• Lab tests. It involves analysing the fluid that is derived that is derived from lesions, or dried scabs. These samples can be tested for the presence of the virus with the polymerase chain reaction (PCR) testing.
• Biopsy. A biopsy involves taking the skin tissue and testing it for virus.

The tests for blood aren’t usually advised. The reason is that the monkeypox virus remains in blood for only a brief period of time. This means it’s not a reliable test to determine if you have monkeypox.

Monkeypox virus pics/monkeypox virus images

References

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• Cho CT, Wenner HA. Monkeypox virus. Bacteriol Rev. 1973 Mar;37(1):1-18. doi: 10.1128/br.37.1.1-18.1973. PMID: 4349404; PMCID: PMC413801.
• Sklenovská, N. (2020). Monkeypox Virus. In: Malik, Y.S., Singh, R.K., Dhama, K. (eds) Animal-Origin Viral Zoonoses. Livestock Diseases and Management. Springer, Singapore. https://doi.org/10.1007/978-981-15-2651-0_2
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