Mpox (Monkeypox)

Overview

Mpox (formerly known as monkeypox Monkeypox A viral disease infecting primates and rodents. Its clinical presentation in humans is similar to smallpox including fever; headache; cough; and a painful rash. It is caused by monkeypox virus and is usually transmitted to humans through bites or via contact with an animal’s blood. Interhuman transmission is relatively low (significantly less than smallpox). Orthopoxvirus) is a viral zoonotic disease caused by the mpox virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology. Mpox has a clinical profile similar to that of smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus, but is less often fatal.

Virology Virology Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology

• Belongs to the genus Orthopoxvirus Orthopoxvirus Orthopoxvirus is a genus of large, brick-shaped, double-stranded DNA viruses. Several clinically relevant species exist, including variola virus (the cause of smallpox), monkeypox virus, vaccinia virus, and cowpox virus. Transmission varies depending on the species but can be through contact with infected bodily secretions, skin lesions, or fomites. Orthopoxvirus of the family Poxviridae Poxviridae A family of double-stranded DNA viruses infecting mammals (including humans), birds and insects. There are two subfamilies: chordopoxvirinae, poxviruses of vertebrates, and entomopoxvirinae, poxviruses of insects. Orthopoxvirus, which also includes smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus and vaccinia Vaccinia The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. Orthopoxvirus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology
• Enveloped double-stranded DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology 
• 2 different clades of the virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology have been identified in various geographical regions of Africa:
  • One endemic to West Africa 
  • One endemic to the Congo Basin

Epidemiology

• First isolated in Denmark in the late 1950s during ongoing research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest in laboratory monkeys
• 1st human case recorded in 1970
• Most cases have occurred in Central and West Africa.
• Prior to 2022, cases in other places were related mostly to international travel from endemic regions. 
• 2022 global outbreak:
  • 1st reported in May 2022 in Europe 
  • On July 23, 2022, the WHO declared the outbreak a public health emergency of international concern.
  • > 54,000 cases of the virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology have been reported from across the world, including 15 deaths (as of August 2022).
  • Most cases (94%) have been attributed to sexual activity in gay, bisexual, and other men who have sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria with men (MSM). 
  • Approximately 41% of the infected individuals had HIV HIV Anti-HIV Drugs.

Transmission

• Animal-to-human transmission:
  • Via an animal bite or infected bodily fluids (blood or cutaneous or mucosal lesions)
  • Inadequately cooked meat is a possible risk.
  • Animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic found to have mpox infection:
    • Monkeys
    • Rope and tree squirrels
    • Gambian pouched rats
    • Dormice 
• Human-to-human transmission:
  • Direct contact through rash Rash Rocky Mountain Spotted Fever, scabs, bodily fluids
  • Respiratory secretions (prolonged hours of contact required) 
  • Indirect transmission through infected materials (clothing, bedding, or towels) and contaminated fomites Fomites Inanimate objects that carry pathogenic microorganisms and thus can serve as the source of infection. Microorganisms typically survive on fomites for minutes or hours. Common fomites include clothing, tissue paper, hairbrushes, and cooking and eating utensils. Adenovirus 
  • Transplacental ( congenital Congenital Chorioretinitis mpox)
• Infection risks:
  • An infected person is potentially infectious from symptom onset ( prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache period) until crusting of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions.
  • Because of the cessation of smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination, people < 50 years of age are more susceptible to infection.
    • Although the smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination provides protection (85% cross-protection) against mpox disease, its duration is unknown.
    • In Spain, 32% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship were reported to have received the smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination in childhood.
  • Those with immune deficiencies are at risk for worse outcomes.

Clinical Presentation

General

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: 4–21 days
• Duration: typical illness lasts 2–4 weeks

Invasion period (0–5 days)

Symptoms occurring during this period may include:

• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever 
• Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess 
• Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy 
• Back pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 
• Myalgia Myalgia Painful sensation in the muscles. Ion Channel Myopathy 
• Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia/asthenia
• Respiratory symptoms, including:
  • Sore throat Sore throat Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis
  • Cough
  • Nasal congestion

Cutaneous manifestations

The course of illness is followed by the development of a rash Rash Rocky Mountain Spotted Fever with the following characteristics:

• Appears within 2–5 days of the onset of disease 
• Progression: Flat lesions (macules) → papules (raised, firm lesions) → vesicles Vesicles Female Genitourinary Examination (fluid-filled lesions) → pustules (lesions with pus)
• Characteristics of lesions:
  • Deep-seated
  • Firm
  • Well circumscribed
  • Often umbilicated
• Possible sites:
  • Face
  • Palm and soles
  • Mucous membranes 
  • Genitalia
  • Note: Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have lesions on only 1 body site.
• Distribution:
  • Typically more lesions on the extremities and face
  • Lesions on genitalia have been commonly seen in the 2022 outbreak.
• Development:
  • Lesions on a single site usually are of the same stage (e.g., pustules on face).
  • 2022 outbreak:
    • Progression of lesions can be rapid.
    • Papulovesicular and pustular lesions may occur on the same site.
• Associated symptoms:
  • Lesions are often painful.
  • Itching occurs in the healing phase (crusts).
• Illness is generally self-limited; blisters crust Crust Dried exudate of body fluids (blood, pus, or sebum) on an area of damaged skin Secondary Skin Lesions over and fall off.

Additional presentations

Other findings in the 2022 outbreak include:

• Individuals, particularly those who engaged in anal-receptive sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria, presented with:
  • Purulent or bloody stools 
  • Rectal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 
  • Rectal bleeding
• Others presented with mucosal lesions:
  • Pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis
  • Epiglottitis Epiglottitis Epiglottitis (or “supraglottitis”) is an inflammation of the epiglottis and adjacent supraglottic structures. The majority of cases are caused by bacterial infection. Symptoms are rapid in onset and severe. Epiglottitis
  • Oral or tonsillar lesions
  • Conjunctival mucosa lesions

Complications

• Complications are rare; they include:
  • Scar Scar Dermatologic Examination formation
  • Secondary bacterial infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • Corneal infection → blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity 
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia 
  • Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis 
  • Death is very rare ( mortality Mortality All deaths reported in a given population. Measures of Health Status rate: 1%–11%).
• Risk factors for complications:
  • Age < 8 years
  • Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis state
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Atopic dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema)/exfoliating disease

Diagnosis

General

Clinicians should suspect mpox in cases with clinical and epidemiologic factors:

• Clinical presentation:
  • Rash Rash Rocky Mountain Spotted Fever
  • Prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache (e.g., fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy)
  • Atypical symptoms (e.g., proctitis Proctitis Inflammation of the mucous membrane of the rectum, the distal end of the large intestine. Chronic Granulomatous Disease)
• Epidemiologic risk factors:
  • Travel history (Central or West Africa or countries with outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza)
  • Contact with:
    • A known infected individual
    • A community known to be at risk of infection (including MSM)
    • Animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic (or animal products) known to be infected

Laboratory evaluation

• Polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)) test for orthopoxvirus Orthopoxvirus Orthopoxvirus is a genus of large, brick-shaped, double-stranded DNA viruses. Several clinically relevant species exist, including variola virus (the cause of smallpox), monkeypox virus, vaccinia virus, and cowpox virus. Transmission varies depending on the species but can be through contact with infected bodily secretions, skin lesions, or fomites. Orthopoxvirus DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure:
  • Swabs are taken from the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions to identify viral DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure.
  • Vigorously swab across lesions
• Mpox virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology real-time PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) test:
  • Originally in the US, PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) testing for orthopoxvirus Orthopoxvirus Orthopoxvirus is a genus of large, brick-shaped, double-stranded DNA viruses. Several clinically relevant species exist, including variola virus (the cause of smallpox), monkeypox virus, vaccinia virus, and cowpox virus. Transmission varies depending on the species but can be through contact with infected bodily secretions, skin lesions, or fomites. Orthopoxvirus DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure is done in laboratory response networks, with mpox virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology characterization done at the CDC.
  • The US Food and Drug Administration issued an emergency use authorization (September 2022) for the Quest Diagnostics Monkeypox Monkeypox A viral disease infecting primates and rodents. Its clinical presentation in humans is similar to smallpox including fever; headache; cough; and a painful rash. It is caused by monkeypox virus and is usually transmitted to humans through bites or via contact with an animal’s blood. Interhuman transmission is relatively low (significantly less than smallpox). Orthopoxvirus Virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology Qualitative Real-Time PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR). 
  • Detects non-variola orthopoxviruses and mpox virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology (West African clade) DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure using swab specimens
  • Specimen collection is still performed in approved health care centers.
• Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus (anti-orthopoxvirus IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions):
  • Positive from days 4–56 after rash Rash Rocky Mountain Spotted Fever onset
  • Can be used to identify the infection and support the diagnosis

Management

Treatment

Principles of treatment:

• Mpox is a self-limiting Self-Limiting Meningitis in Children disease, with most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship recovering without any medical intervention. 
• Supportive care can be given in the form of:
  • Fluids
  • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways management
• Antivirals are indicated for people with (or risk factors for) severe disease.

Consider antiviral Antiviral Antivirals for Hepatitis B treatment for:

• Severe disease:
  • Hemorrhagic lesions
  • Confluent lesions
  • Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis
  • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
  • Health status requiring hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
• At risk for severe disease:
  • Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis individuals (e.g., people with HIV HIV Anti-HIV Drugs, malignancy Malignancy Hemothorax, leukemia)
  • Children, especially those < 8 years of age
  • Pregnant or breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding women
  • Individuals with atopic dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema) or exfoliative skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions disease
  • Individuals with ≥ 1 complication

Treatments available:

• Tecovirimat Tecovirimat Orthopoxvirus (TPOXX):
  • Antiviral Antiviral Antivirals for Hepatitis B developed for smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus
  • Potent inhibitor of orthopoxvirus Orthopoxvirus Orthopoxvirus is a genus of large, brick-shaped, double-stranded DNA viruses. Several clinically relevant species exist, including variola virus (the cause of smallpox), monkeypox virus, vaccinia virus, and cowpox virus. Transmission varies depending on the species but can be through contact with infected bodily secretions, skin lesions, or fomites. Orthopoxvirus protein required for dissemination
  • Treatment of choice
  • Available in oral and IV preparations
• Cidofovir Cidofovir An acyclic nucleoside phosphonate that acts as a competitive inhibitor of viral DNA polymerases. It is used in the treatment of retinitis caused by cytomegalovirus infections and may also be useful for treating herpesvirus infections. Antivirals for Herpes Virus:
  • Alternative agent 
  • Showed in vitro activity against mpox virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology and found to be effective in animal models
• Brincidofovir:
  • Prodrug Prodrug Nitroimidazoles of cidofovir Cidofovir An acyclic nucleoside phosphonate that acts as a competitive inhibitor of viral DNA polymerases. It is used in the treatment of retinitis caused by cytomegalovirus infections and may also be useful for treating herpesvirus infections. Antivirals for Herpes Virus
  • Approved for treatment of smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus 
• Trifluridine (eye drops or ointments):
  • Approved for herpes keratitis Keratitis Inflammation of the cornea. Herpes Simplex Virus 1 and 2/ keratoconjunctivitis Keratoconjunctivitis Simultaneous inflammation of the cornea and conjunctiva. Stevens-Johnson Syndrome
  • Can be used for mpox with eye involvement
• Vaccinia Vaccinia The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. Orthopoxvirus Immune Globulin Intravenous (VIGIV):
  • Used for vaccinia Vaccinia The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. Orthopoxvirus vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination complications
  • CDC allows VIGIV use for outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza due to orthopoxvirus Orthopoxvirus Orthopoxvirus is a genus of large, brick-shaped, double-stranded DNA viruses. Several clinically relevant species exist, including variola virus (the cause of smallpox), monkeypox virus, vaccinia virus, and cowpox virus. Transmission varies depending on the species but can be through contact with infected bodily secretions, skin lesions, or fomites. Orthopoxvirus

Prevention and isolation

Prevention:

• Avoid:
  • Contact with infected animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic
  • Contact with exposed individuals and/or individuals with rashes Rashes Rashes are a group of diseases that cause abnormal coloration and texture to the skin. The etiologies are numerous but can include irritation, allergens, infections, or inflammatory conditions. Rashes that present in only 1 area of the body are called localized rashes. Generalized rashes occur diffusely throughout the body. Generalized and Localized Rashes
  • Contact with contaminated material and fomites Fomites Inanimate objects that carry pathogenic microorganisms and thus can serve as the source of infection. Microorganisms typically survive on fomites for minutes or hours. Common fomites include clothing, tissue paper, hairbrushes, and cooking and eating utensils. Adenovirus (e.g., bedding, clothing, linens) 
  • Sexual contact with anonymous partners
• Frequent handwashing
• Use wet cleaning methods (avoid dusting, sweeping, and vacuuming)
• Health care personnel should use appropriate safety measures and wear PPE:
  • Gown
  • Gloves
  • Eye protection (goggles or face shields should cover front and side of the face)
  • National Institute for Occupational Safety and Health (NIOSH)–approved particulate respirator with N95 filter (or higher)

Isolation:

• Those in whom mpox is suspected → institute isolation measures until mpox is ruled out
• Those with confirmed mpox → start and maintain isolation measures until all crusts are separated and a new layer of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions has developed
• Measures:
  • Isolate until all symptoms resolve (usually 2–4 weeks after onset of symptoms)
  • Isolate away from household members and pets:
    • Ideally, in a separate room
    • Avoid physical contact at all times
  • Do not share items with people or animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic until all signs and symptoms have resolved.
  • Wear a well-fitting mask and cover lesions (with gloves, gauze, or clothing).
  • Disinfect/launder potentially contaminated items.
  • Frequent handwashing (or use of an alcohol-based sanitizer) is recommended.
  • Avoid contact lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy use (as this can spread the infection to the eyes).
  • Avoid shaving in affected areas (can lead to autoinoculation Autoinoculation Molluscum Contagiosum).
  • Avoid public transportation (even when seeking medical care Medical care Conflict of Interest).

After recovery:

• Safe sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria practices (e.g., use of condoms Condoms A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. Nonhormonal Contraception) are recommended, but it is still unknown for how long.
• Other countries recommend use of protection for at least 8 weeks.

Management of exposure and contacts

Anyone in contact or who provided care for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with mpox should monitor themselves for symptoms:

• ≤ 21 days from the last date of exposure/contact
• Monitor temperature twice daily.
• If a rash Rash Rocky Mountain Spotted Fever develops, immediately self-isolate and contact a health care provider.
  • Evaluation and testing are needed.
  • Follow isolation measures until results are available and are negative.
• If other symptoms develop (without rash Rash Rocky Mountain Spotted Fever), continue to isolate and observe for 5 days (even if this goes beyond the 21 days after exposure).
  • Generally, a rash Rash Rocky Mountain Spotted Fever would be expected in the 5-day period.
  • Thoroughly examine for skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and oral lesions.
  • If 5 days pass without any new symptoms or rash Rash Rocky Mountain Spotted Fever, isolation can be discontinued.

Vaccines

Vaccines developed against smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus can also be used against mpox. 

• JYNNEOS:
  • Produced from the strain Modified Vaccinia Vaccinia The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. Orthopoxvirus Ankara—Bavarian Nordic (MVA-BN), a highly attenuated, nonreplicating orthopoxvirus Orthopoxvirus Orthopoxvirus is a genus of large, brick-shaped, double-stranded DNA viruses. Several clinically relevant species exist, including variola virus (the cause of smallpox), monkeypox virus, vaccinia virus, and cowpox virus. Transmission varies depending on the species but can be through contact with infected bodily secretions, skin lesions, or fomites. Orthopoxvirus
  • Approved for prevention of smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus and mpox in the US.
  • Preferred vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination
• ACAM2000: 
  • Replicant vaccinia Vaccinia The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. Orthopoxvirus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination (live virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology) 
  • Can be used for mpox under an expanded access investigational new drug application through the CDC
• Pre-exposure prophylaxis Prophylaxis Cephalosporins can be given to:
  • People working with orthopoxvirus Orthopoxvirus Orthopoxvirus is a genus of large, brick-shaped, double-stranded DNA viruses. Several clinically relevant species exist, including variola virus (the cause of smallpox), monkeypox virus, vaccinia virus, and cowpox virus. Transmission varies depending on the species but can be through contact with infected bodily secretions, skin lesions, or fomites. Orthopoxvirus in laboratory/ research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest facilities
  • Health care personnel assigned to public health or anti-terrorist response teams
• Post-exposure prophylaxis Prophylaxis Cephalosporins:
  • Known or presumed exposure to a person with confirmed mpox 
  • Recent sexual contact (≤ 14 days) with a partner diagnosed with mpox
  • Gay, bisexual, MSM, or transgender Transgender Persons having a sense of persistent identification with, and expression of, gender-coded behaviors not typically associated with one’s anatomical sex at birth, with or without a desire to undergo sex reassignment procedures. Gender Dysphoria people who engaged in sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria in the following situations (within the past 14 days):
    • Group sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria or multiple partners
    • Commercial sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria venue
    • Activity associated with an event or geographic area where there is mpox transmission

Differential Diagnosis

• Smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus: infection caused by smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology. Smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus is transmitted through respiratory aerosols Aerosols Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellant agents. Coxiella/Q Fever and contact with lesions and fomites Fomites Inanimate objects that carry pathogenic microorganisms and thus can serve as the source of infection. Microorganisms typically survive on fomites for minutes or hours. Common fomites include clothing, tissue paper, hairbrushes, and cooking and eating utensils. Adenovirus. The disease presents with constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis and a diffuse, well-circumscribed maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever with centrifugal spread that eventually scars. Additionally, this infection is associated with a high mortality Mortality All deaths reported in a given population. Measures of Health Status rate. Diagnosis is done through PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) testing, serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus, and electron microscopy. Management is supportive, though antiviral Antiviral Antivirals for Hepatitis B therapy can be used in certain patient populations. 
• Chickenpox Chickenpox A highly contagious infectious disease caused by the varicella-zoster virus. It usually affects children, is spread by direct contact or respiratory route via droplet nuclei, and is characterized by the appearance on the skin and mucous membranes of successive crops of typical pruritic vesicular lesions that are easily broken and become scabbed. Chickenpox is relatively benign in children, but may be complicated by pneumonia and encephalitis in adults. Varicella-Zoster Virus/Chickenpox: a primary infection Primary infection Herpes Simplex Virus 1 and 2 caused by the varicella zoster virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology. The typical clinical presentation includes prodromal symptoms, an oral enanthem Enanthem Varicella-Zoster Virus/Chickenpox, and a generalized, intensely pruritic vesicular rash Rash Rocky Mountain Spotted Fever. The lesions appear in crops and will be in varying stages of evolution. The diagnosis is primarily clinical. Management is supportive, though antiviral Antiviral Antivirals for Hepatitis B therapy can be used in certain patient populations. 
• Herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections infection: Herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology presents with both oral and genital lesions, similar to mpox. Presentation includes systemic features such as fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and myalgia Myalgia Painful sensation in the muscles. Ion Channel Myopathy. Typical mucocutaneous infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are characterized by an acute, localized appearance of clusters of small, painful vesicles Vesicles Female Genitourinary Examination on an erythematous base. The diagnosis is made by clinical history, PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) testing, and serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus. Antiviral Antiviral Antivirals for Hepatitis B agents are used in the management of HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2 infection.