Key Points

• Monkeypox is a zoonotic viral disease spread via direct contact, respiratory secretions, and contaminated materials and surfaces ^r1r2r3r4
• Monkeypox classically presents with rash, fever, lymphadenopathy, and a clinical course similar to that of smallpox but milder ^r3r5r6
• Monkeypox is caused by monkeypox virus, which belongs to the Orthopoxvirus genus of the Poxviridae family; other members of Orthopoxvirus include variola virus (which causes smallpox), vaccinia virus (used in smallpox vaccines), cowpox virus, and various other animal poxviruses ^r1
• WHO has proposed renaming the monkeypox disease and virus, in accordance with current best practices for naming infectious diseases; although no consensus has emerged yet, some alternative names currently in limited use include Mpox, MPV, MPX, MPXV, and hMPXV ^r7r8
• Monkeypox is endemic in several African countries, and until 2022, nearly all reported cases arose in Africa, with rare sporadic cases elsewhere; in 2022, a multi-country outbreak arose in nonendemic countries, including the United States, with atypical clinical presentations and most cases identified in men who have sex with men ^r3r9
  • US has declared the ongoing 2022 multi-country outbreak a public health emergency; CDC provides frequent updates online regarding the domestic outbreak situation ^r10
  • WHO has declared the 2022 multi-country outbreak a public health emergency of international concern, and provides frequent updates online regarding the international outbreak situation ^r9
  • Although the 2022 multi-country outbreak is ongoing, case counts in the United States and worldwide have steadily declined in recent months (as of October 2022) ^r9r11
• Monkeypox should be considered in a patient with appropriate clinical features, especially rash, and epidemiologic risk factors for recent monkeypox exposure; close person to person contact, especially intimate and sexual contact, has been identified as the primary mode of exposure in 2022 outbreak cases ^r12r13
• Classically, there are prodromal symptoms of fever, chills, headache, myalgias, arthralgias, fatigue, and lymphadenopathy, with characteristic rash first appearing within several days of fever; in 2022 outbreak cases these symptoms may be very mild, be absent altogether, be concurrent with rash, or even develop after rash first appears ^r14r15r16r17
• Rash is invariably present in monkeypox, with skin lesions that are typically deep-seated, well-demarcated, and umbilicated; initial lesions in mucosal regions (oral, genital, perianal) have been common in 2022 outbreak cases ^r15r18
• Monkeypox is diagnosed via laboratory detection of monkeypox virus in the setting of appropriate epidemiologic risk factors and clinical findings
• Diagnostic testing for monkeypox should be undertaken in consultation with public health authorities and may consist of either generic orthopox or monkeypox-specific real-time polymerase chain reaction testing of lesion material from swabs; laboratories may forward specimens from positive cases to CDC for further viral characterization and sequencing ^r14r19
• Differential diagnosis for monkeypox includes other, more common causes of localized genital lesions and rash; the overall clinical features of monkeypox are similar to those of smallpox, which has been eradicated worldwide
• Most patients with monkeypox have mild, self-limited disease that can be managed with supportive care; antiviral medications can be considered for patients with severe disease, high risk of severe disease, and infection involving high-risk anatomic areas ^r20
• Currently there are no treatments approved specifically for monkeypox virus infection, but several antiviral agents originally developed for treatment of smallpox and other viral infections may be considered ^r20
• Complicated disease may affect nearly any organ system and result in substantial morbidity and even death; disease course is more severe in persons with immunocompromise, most notably HIV
• Monkeypox case fatality rates of 3% to 6% have previously been reported in African countries where the disease is endemic; the estimated case fatality rate associated with the 2022 multi-country outbreak has been substantially lower, at approximately 0.03% ^r3r9
• Infection control measures, in both health care and home settings, are vital to minimize exposure and infection risk; they include appropriate isolation, hygiene measures, and use of personal protective equipment ^r21r22
• Exposed persons should be monitored for symptoms and have an exposure risk assessment performed; postexposure prophylaxis with smallpox vaccination is recommended for high-risk exposures and can be considered for intermediate-risk exposures ^r23r24
• One vaccine (Jynneos) is licensed in the United States for prevention of monkeypox and smallpox, and another (ACAM2000) is licensed for prevention of smallpox but considered effective for prevention of monkeypox as well; vaccination is recommended as preexposure prophylaxis for certain persons at ongoing significant risk for monkeypox exposure and can be used as postexposure prophylaxis for persons who have had recent confirmed or likely high-risk or intermediate-risk exposures ^r23r24
• CDC Emergency Operations Center (telephone, 1-770-488-7100) is available for consultation regarding appropriate utilization of medical countermeasures for monkeypox and can facilitate obtaining antiviral medications and vaccines from the National Strategic Stockpile

Urgent Action

• Clinicians should be vigilant for rash that may be consistent with monkeypox, particularly in patients with established high-risk epidemiologic features (ie, contact with someone with similar rash or confirmed monkeypox diagnosis, close contact with people in a social network with monkeypox activity, history of recent international travel to country with confirmed cases) ^r12r18
• Suspected monkeypox cases should be reported to relevant hospital and local and state public health authorities (to facilitate necessary reporting and further diagnostic and management steps)

Pitfalls

• Monkeypox cases in the ongoing 2022 outbreak event have had atypical clinical features, including absence of classic prodromal symptoms (including fever and lymphadenopathy) and predilection for initial lesions to appear in the genital and perianal regions ^r15
• Monkeypox lesions in the genital and perianal regions can be easily confused with sexually transmitted infections by patients and clinicians alike, and therefore patients may initially present to outpatient settings such as sexual health clinics for care; coinfections with monkeypox and sexually transmitted diseases have been reported, and presence of a sexually transmitted infection does not preclude monkeypox ^r15r25

Clinical Clarification

• Monkeypox is a zoonotic viral disease spread via direct contact, respiratory secretions, and contaminated materials and surfaces ^r1r2r3r4
• Monkeypox classically presents with rash, fever, lymphadenopathy, and a clinical course similar to that of smallpox but milder ^r3r5r6r26
• Monkeypox is caused by monkeypox virus, which belongs to the Orthopoxvirus genus of the Poxviridae family; other members of Orthopoxvirus include variola virus (which causes smallpox), vaccinia virus (used in smallpox vaccines), cowpox virus, and various other animal poxviruses ^r1r2r4
• Monkeypox is so named as it was first detected in monkeys; the natural host reservoir remains unknown, but rodents and other small mammals are most frequently implicated ^r1r2r4
• WHO has proposed renaming the monkeypox disease and virus, in accordance with current best practices for naming infectious diseases and pathogens; although no consensus has emerged yet, some alternative names currently in limited use include Mpox, MPV, MPX, MPXV, and hMPXV ^r7r8
• Monkeypox is endemic in several African countries, and until 2022, nearly all reported cases arose in Africa, with rare sporadic cases elsewhere; in 2022, a multi-country outbreak arose in nonendemic countries, including the United States, with atypical clinical features and most cases identified in men who have sex with men ^r9
  • First known significant outbreak of human monkeypox in the United States was in 2003 and involved 47 confirmed and probable cases that were traced to infected pet prairie dogs; no more outbreaks occurred in the United States until the 2022 outbreak ^r5r6
  • US has declared the ongoing 2022 multi-country outbreak a public health emergency; CDC provides frequent updates online regarding the domestic outbreak situation ^r10
  • WHO has declared the 2022 multi-country outbreak a public health emergency of international concern; it provides frequent updates online regarding the international outbreak situation ^r9
  • Although the 2022 multi-country outbreak is ongoing, case counts in the United States and worldwide have steadily declined in recent months (as of October 2022) ^r9r11
• Monkeypox case fatality rates of 3% to 6% have previously been reported in African countries where the disease is endemic; the estimated case fatality rate associated with the 2022 multi-country outbreak has been substantially lower, at approximately 0.03% ^r3r9

Classification

• CDC case definitions ^r12
  • Suspect case
    • New rash characteristic of monkeypox or
    • Meets 1 epidemiologic criterion within 21 days of symptom onset and high clinical suspicion for monkeypox
  • Probable case
    • Criteria met for suspect case and
    • No other known recent orthopoxvirus exposure (eg, via smallpox vaccination) and
    • Orthopoxvirus infection confirmed by one of the following:
      • Detection of orthopoxvirus DNA by polymerase chain reaction testing of a clinical specimen or
      • Presence of orthopoxvirus demonstrated by immunohistochemistry or electron microscopy or
      • Detection of anti-orthopoxvirus IgM antibody between 4 and 56 days after rash onset
    • CDC has stated that for the ongoing 2022 outbreak, all confirmed orthopoxvirus infection cases in the United States are presumed to be monkeypox unless proven otherwise ^r15
  • Confirmed case
    • Criteria met for suspect case and
    • Monkeypox infection confirmed by one of the following:
      • Detection of monkeypox virus DNA by polymerase chain reaction testing or next-generation sequencing of a clinical specimen or
      • Isolation of monkeypox virus in culture from a clinical specimen
• WHO case definitions for the ongoing 2022 multi-country outbreak event are slightly different, as follows: ^r27
  • Suspected case
    • Known contact with probable or confirmed monkeypox case within 21 days of developing any of the following symptoms:
      • Acute onset of fever
      • Headache
      • Myalgia
      • Back pain
      • Lymphadenopathy
      • Profound weakness
    • Or presentation with unexplained acute rash, mucosal lesions, or lymphadenopathy that cannot be explained by other common causes of rash
  • Probable case
    • Unexplained acute rash, mucosal lesions, or lymphadenopathy and
    • One or more of the following:
      • Confirmed epidemiologic connection to a probable or confirmed monkeypox case within 21 days of symptom onset
      • Patient identifies as gay, bisexual, or other man who has sex with men
      • Multiple or casual sexual partners within 21 days of symptom onset
      • Detection of anti-orthopoxvirus IgM antibody between 4 and 56 days after rash onset, or a four-fold rise in IgG antibody titers based on acute samples (up to days 5-7) and convalescent samples (after day 21), in the absence of other known orthopoxvirus exposure (eg, via smallpox vaccination)
      • Confirmed orthopoxvirus infection (eg, via polymerase chain reaction or sequencing)
  • Confirmed case
    • Criteria met for suspected or probable case
    • Laboratory confirmation of monkeypox infection via real-time polymerase chain reaction or sequencing of monkeypox viral DNA

Clinical Presentation

Causes and Risk Factors

Diagnostic Procedures

Differential Diagnosis

Goals

• Supportive care for all patients; supportive care alone suffices for many patients with monkeypox
• Antiviral treatment to ameliorate severe disease and reduce risk for patients with high risk of severe disease or high-risk disease features
• Management of specific disease manifestations and complications of disease

Disposition

Treatment Options

Most patients with monkeypox have mild, self-limited disease, which can be managed with supportive care alone ^r20

Consider systemic antiviral treatment for the following patients after consultation with state health authorities or CDC through the Emergency Operations Center (telephone, 1-770-488-7100): ^r20

• Patients with severe disease or severe disease-related complications (eg, hemorrhagic disease, confluent lesions, sepsis, encephalitis, ocular disease, bronchopneumonia, or other conditions requiring hospitalization)
• Patients at high risk of severe disease, such as those with significant immunocompromise or certain preexisting skin conditions, children, pregnant or breastfeeding adults
• Patients with infection involving high-risk anatomic areas (eg, eyes, mouth, genitals, anus) with potential for serious adverse outcomes

Currently there are no treatments approved specifically for monkeypox virus infection, but several antiviral agents originally developed for treatment of smallpox and other viral infections may be considered and obtained from the Strategic National Stockpile upon request from state health authorities after consultation with CDC. Efficacy data for these agents are lacking, owing to infeasibility of human smallpox experimentation ^r20

• Tecovirimat ^r51r52
  • Approved for treatment of human smallpox disease in adults and children weighing at least 3 kg
  • CDC has an EA-IND protocol (expanded access–investigational new drug) that allows use in treatment of monkeypox in an outbreak
  • Demonstrated efficacy against a diverse range of orthopoxviruses per in vitro and in vivo animal studies; efficacy data for treating monkeypox in humans is unavailable ^r53
  • Preferred therapy for most patients in whom systemic antiviral treatment is indicated, including patients with HIV, pregnant or breastfeeding patients, and pediatric patients
  • Instructions on obtaining and using tecovirimat, as well as required forms, are available at the CDC website ^r52r54
    • Tecovirimat is available through the Strategic National Stockpile upon request from state and territorial health departments; certain states and territories have pre-positioned supplies to facilitate faster access
    • CDC has streamlined the process for health care professionals to provide tecovirimat treatment for patients with monkeypox under its EA-IND protocol ^r54
      • Treatment can begin upon receipt of the medication, after informed consent is obtained
      • Required forms under the EA-IND can be returned to CDC after treatment begins
  • Available in capsule and injection form
  • Injection is contraindicated in severe renal impairment
  • A recent report on clinical use of tecovirimat for treatment of monkeypox infection under the CDC EA-IND protocol found that among 549 treated patients, 99.8% were prescribed oral tecovirimat, 93.1% were not hospitalized, and very few adverse events were reported overall ^r55
• Cidofovir ^r56
  • Originally approved for treatment of cytomegalovirus in patients with AIDS; has been used for other viral infections
  • CDC has an EA-IND protocol that allows use in treatment of monkeypox in an outbreak
  • IV infusion; must be administered with probenecid
  • BLACK BOX WARNINGS for renal impairment and neutropenia
  • Contraindicated in patients with severe renal impairment, those receiving potentially nephrotoxic agents, and those with hypersensitivity to cidofovir or severe hypersensitivity to probenecid or other sulfa-containing medications
• VIGIV (vaccinia immune globulin intravenous) ^r57
  • Approved for treatment of complications due to vaccinia vaccination
  • CDC has an EA-IND protocol that allows use in treatment of monkeypox in an outbreak
  • For IV use only
  • BLACK BOX WARNING for interactions with glucose monitoring systems
    • Measure blood glucose level with a glucose-specific method during VIGIV therapy; VIGIV contains maltose and may falsely elevate glucose readings with some types of glucose monitoring systems
  • Contraindicated in patients with history of anaphylaxis or other severe reaction to IV immune globulin, and in IgA-deficient patients with anti-IgA antibodies and history of IgA hypersensitivity
• Brincidofovir ^r58
  • Approved for treatment of human smallpox disease in adults and children, including neonates
  • CDC is currently developing an EA-IND protocol to facilitate use in treatment of monkeypox; not currently available from the Strategic National Stockpile at this time
  • Available in tablet and oral suspension form
  • BLACK BOX WARNING for increased mortality risk when used for prolonged durations
  • No contraindications noted in prescribing information
• Trifluridine ^r59
  • Approved for treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2
  • Has demonstrated in vitro activity against orthopoxviruses; has been the preferred treatment for ocular vaccinia infection resulting as complication of smallpox vaccination with ACAM2000 vaccine ^r30
  • May be considered for use in patients with ocular monkeypox involvement; prophylactic use can be considered for patients with eye-adjacent lesions ^r60
  • For topical ophthalmic use only
  • Contraindicated in patients who develop hypersensitivity reactions or chemical intolerance to trifluridine

Other management considerations should be individualized depending on specific monkeypox disease manifestations or disease-related complications, and may include the following: ^r61r62

• Fever
  • Antipyretic medications and external cooling measures
• Pain
  • Topical steroids, topical anesthetic agents, OTC analgesics (eg, acetaminophen, NSAIDs), and prescription analgesics (eg, gabapentin, opioids)
• Inflammation/lymphadenopathy
  • Antiinflammatory and analgesic medications
• Pruritus/itching
  • Oral antihistamines; topical agents such as calamine lotion
• Oropharyngeal lesions
  • Mucosal care, saltwater rinses, oral antiseptic mouthwash, local anesthetic agents, prescription analgesic mouthwash
• Rectal lesions
  • Stool softeners, warm sitz baths, general pain control measures
• Genital lesions
  • General pain control measures, topical steroids for localized swelling
• Vomiting/diarrhea
  • Oral or IV hydration and antiemetic/antidiarrheal medications
• Respiratory tract
  • Suctioning, incentive spirometry, chest physiotherapy, bronchodilators, antibiotics for secondary respiratory infections, nebulizer treatments, bronchoscopy, noninvasive ventilation, intubation/ventilation
• Sepsis
  • Antibiotics, IV fluids, vasopressors, supplemental oxygen
• Skin compromise
  • Cleaning, moist dressings, topical antibiotics, surgical debridement, skin grafts
• Secondary skin infection
  • Antibiotics, incision and drainage, advanced wound management

CDC has developed more detailed clinical guidance for the following specific clinical scenarios:

• Ocular involvement ^r60
  • Ocular involvement is an uncommon but potentially serious manifestation of monkeypox infection
  • Though high rates of ocular involvement have been reported with endemic monkeypox disease, less than 1% of individuals in the ongoing outbreak have had eye involvement
  • Ocular disease may result in a range of ocular complications, including corneal scarring and loss of vision; bacterial superinfection may also result in severe adverse outcomes
  • Ophthalmologic consultation should be obtained urgently if ocular monkeypox involvement is suspected, and a comprehensive ophthalmic examination should be performed, with appropriate isolation protocols and personal protective equipment in place
  • Systemic antiviral therapy should be considered for patients severe monkeypox disease or severe disease-related complications, which include eye involvement
  • Though efficacy data is lacking, tecovirimat is frequently given for systemic therapy; VIGIV may also be considered after consultation with CDC
  • Topical antiviral therapy with trifluridine may be considered in consultation with an ophthalmologist; prophylactic treatment with topical trifluridine can also be considered for patients with eye-adjacent lesions
  • Topical lubricants and antibiotics can be considered to prevent bacterial superinfection; topical steroids may exacerbate corneal damage and should be avoided

Complications

• Pitted scarring (pockmarks) is the most common long-term sequela for survivors ^r32
• Oral lesions and regional lymphadenopathy can lead to difficulties with swallowing and thus with eating and drinking ^r32
• Vomiting and diarrhea, resulting in severe dehydration ^r32
• Perianal lesions can lead to severe pain, tenesmus, and bleeding ^r30
• Secondary bacterial infections of skin ^r32
• Secondary infections of lungs, resulting in bronchopneumonia and respiratory distress, potentially requiring intubation ^r32
• Neurologic complications including encephalitis and transverse myelitis ^r32r49
• Cardiac complications including myocarditis and pericardial disease ^r49
• Urologic complications including urethritis and penile necrosis ^r49
• Septicemia ^r32
• Hemodynamic instability requiring vasopressor support ^r49
• Ocular infections, which can result in corneal scarring and permanent vision loss ^r32

Prognosis

• Monkeypox has a mild, self-limited course for most patients ^r5r6r30
• Monkeypox case fatality rates of 3% to 6% have previously been reported in African countries where the disease is endemic; the estimated case fatality rate associated with the 2022 multi-country outbreak has been substantially lower, at approximately 0.03% ^r5r6r9
• Mortality is higher in children and young adults; disease is more severe in persons with immunocompromise, most notably HIV ^r2r49

Prevention

• General infection control measures ^r71r72
  • Avoid close, skin to skin contact, including intimate or sexual contact, with anyone that has a monkeypox-like rash ^r40
  • Avoid contact with potentially infected animals or animal products
  • Avoid contact with items or materials that have been in contact with sick animals or people
  • Isolate infected patients
  • Appropriate hand hygiene
  • Use appropriate personal protective equipment when caring for patients or collecting specimens for diagnosis
• Infection control in home settings ^r21
  • Isolation and personal protective equipment
    • Patients who do not require hospital admission may isolate at home
    • Patients should not leave the home except for emergencies or necessary medical care
    • Visitors should refrain from visiting during the isolation period
    • Patients should isolate separately from and avoid close contact with other household members and pets; patients and household members should both wear medical masks when close contact is necessary or cannot be avoided
    • A separate bathroom should be used if possible
    • Patients should manage their own wound care, linens, and laundry if possible, using disposable gloves and appropriate hand hygiene; if assistance from household members is required, disposable medical gloves and a medical mask should be used
    • Skin lesions should be covered as much as much as possible, with long sleeves, long pants, and gloves
    • Patients should avoid use of contact lenses and shaving rash-covered areas to prevent further spread of lesions
  • Hand hygiene and household disinfection ^r73
    • Potentially contaminated personal items (eg, clothing, linens, towels, dishes, utensils) should be washed properly and not shared
    • Frequently touched surfaces, such as counters and light switches, should be regularly cleaned and disinfected
    • Hand hygiene, with an alcohol-based hand rub or soap and water, should be performed after any contact with rash material or potentially contaminated materials and surfaces
    • If use of a separate bathroom is not possible, potentially contaminated surfaces should be cleaned and disinfected after each use of the shared space
    • CDC has published detailed guidance for household cleaning and disinfection of monkeypox ^r73
  • Sexual activity
    • Patients should refrain from all sexual activity during the isolation period ^r25
    • Barrier practices (eg, condoms) are recommended after recovery; data to guide duration are sparse, but some countries recommend at least 8 weeks ^r25
  • Isolating with animals in the home ^r21r74
    • Patients with monkeypox should avoid contact with mammals, including pets
    • Potentially contaminated materials, including bandages, linens, and laundry, should be kept away from domestic animals
  • Infection control precautions should be maintained until all lesions have scabbed off, separated, and healed with a fresh layer of intact skin, or until cleared by public health authorities ^r38
• Infection control in health care settings ^r22
  • Regarding prevention of monkeypox transmission in health care settings, CDC references 2007 guidelines for preventing transmission of infectious agents in these settings ^r75
  • Patients with suspected or confirmed monkeypox infection should be placed in single-person rooms with standard precautions; special air handling is not necessary unless high-risk procedures are performed
  • Visitation should be limited to that which is necessary for patient care and wellbeing
  • Intubation, extubation, and any high-risk procedures likely to spread oral secretions should be performed in airborne isolation rooms
  • Personal protective equipment for health care staff entering the patient's room should include gown, gloves, eye protection, and N95-comparable or higher-level respirator
  • Waste management should be performed in accordance with hazardous materials regulations
  • Soiled laundry should be managed in accordance with recommended standard practices for environmental infection control ^r76
  • Cleaning and disinfection should be performed using hospital-grade disinfectant with an emerging viral pathogen claim
  • Wet cleaning methods are preferred; dry dusting, sweeping, and vacuuming should be avoided
  • Infection control precautions should be maintained until monkeypox infection is ruled out in patients in whom it is suspected, or until all lesions have scabbed off, separated, and healed with a fresh layer of intact skin for those with confirmed monkeypox infection; consultation with local or state health department might be necessary, depending on locale ^r38
• Safer sex practices
  • Male to male sexual contact between gay, bisexual, and other men who have sex with men appears to be the primary mode of transmission in the ongoing 2022 outbreak; various harm reduction efforts have focused on safer sex practices in these populations ^r9
  • CDC has issued recommendations for safer sexual practices to help reduce the risk of monkeypox exposure and transmission, including: ^r39
    • Taking a break from potential high-risk sexual behaviors, until completion of vaccination for monkeypox
    • Limiting number of sexual partners
    • Avoiding venues such as sex clubs and sex parties, where anonymous sexual contact with multiple partners occurs
    • Use of barrier protection such as condoms
    • Avoidance of kissing or exchanging saliva
    • Reducing as much skin to skin contact as possible during sexual activity
    • Virtual or touchless sexual activities
    • Washing hands, sex toys, and potentially contaminated fabrics (eg, bedding, towels, clothes) after sex
  • WHO previously issued public health advice for gay, bisexual, and other men who have sex with men, with recommendations to: ^r40
    • Isolate at home and seek medical attention if symptoms develop
    • Avoid close contact, including sexual contact, with anyone with symptoms
    • Clean hands, objects, and surfaces that have been touched regularly
    • Wear a mask if in close contact with anyone with symptoms
  • Modeling of sexual transmission between gay, bisexual, and other men who have sex with men has indicated that reductions in one-time sexual encounters can significantly reduce transmission ^r39r77
  • In August 2022, in an online survey of gay, bisexual, and other men who have sex with men, respondents reported adopting the following strategies to prevent potential monkeypox transmission in light of the ongoing outbreak: ^r78
    • 48% reported reducing number of sexual partners
    • 50% reported reducing one-time sexual encounters
    • 50% reported reducing sex with partners from dating apps or sex venues
• Exposure management
  • Exposures in the community ^r23
    • Confer with appropriate public health authorities when monitoring of exposed contacts is undertaken ^r15
    • Exposure risk assessment should be performed to determine possible need for postexposure prophylaxis
    • Contacts with confirmed monkeypox exposure should monitor for the following signs and symptoms of infection for 21 days after the last exposure:
      • New rash, including oral, genital, and anal lesions
      • Fever
      • Chills
      • Lymphadenopathy
      • Fatigue
      • Myalgias and backache
      • Headache
      • Respiratory symptoms
    • Asymptomatic contacts can continue routine daily activities during the monitoring period but should not donate blood, bodily fluids, cells, tissues, or organs during that period
    • If rash develops during the monitoring period, contacts should self-isolate until rash can be evaluated by a health care professional and monkeypox is ruled out
    • If other symptoms develop during the monitoring period, contacts should isolate at home for 5 days and monitor for emergence of new symptoms; if no new symptoms develop and no skin or oral lesions appear during the 5-day period, isolation can stop
  • Exposures in health care settings ^r22
    • Notify hospital infection control when monitoring of exposed patients is undertaken
    • Asymptomatic exposed patients do not need to be isolated, but should be monitored
    • Exposure risk assessment should be performed to determine possible need for postexposure prophylaxis
    • Monitoring should include at least daily assessment of potential signs and symptoms of monkeypox for 21 days after the last exposure, inclusive of a thorough skin and oral examination
    • If rash develops during the monitoring period, the patient should be placed on empiric isolation precautions for monkeypox until rash is evaluated and monkeypox has been ruled out
    • If other symptoms develop during the monitoring period, the patient should be placed on empiric isolation precautions for monkeypox and monitored for 5 days for the emergence of new symptoms; if no new symptoms develop and no skin or oral lesions appear during the 5-day period, isolation precautions can be discontinued
  • Exposed health care professionals ^r22
    • Confer with applicable public health and occupational health authorities to guide decisions on monitoring exposed health care professionals
    • Exposure risk assessment should be performed to determine possible need for postexposure prophylaxis
    • Asymptomatic health care professionals may continue to work but should monitor for signs and symptoms of monkeypox for 21 days after the last exposure
    • If rash develops during the monitoring period, the person should not go to work until rash is evaluated and monkeypox has been ruled out
    • If other symptoms develop during the monitoring period, the person should not go to work for 5 days and should monitor for emergence of new symptoms; if no new symptoms develop and no skin or oral lesions appear during the 5-day period, the person may return to work if cleared by occupational health physician
  • Exposure risk assessment and postexposure prophylaxis ^r22r23
    • Exposure risk assessment for all persons with potential monkeypox exposure should be performed to determine need for postexposure prophylaxis
    • Management recommendations depend on degree of exposure:
      • High-risk: symptom monitoring is necessary; postexposure prophylaxis with ACAM2000 or Jynneos vaccination is recommended
        • High-risk exposures include:
          • Community settings:
            • Contact between an exposed person's broken skin or mucous membranes and the skin lesions, bodily fluids, or potentially contaminated materials (eg, linens, clothing, sex toys) from a person with monkeypox or
            • Any sexual or intimate contact involving the mucous membranes of a person with monkeypox
          • Health care settings:
            • Unprotected contact between an exposed person's broken skin or mucous membranes and the skin lesions, bodily fluids, or potentially contaminated materials (eg, linens, clothing) from a patient with monkeypox or
            • Being inside the patient's room or within 6 feet of a patient with monkeypox during aerosol-generating procedures without wearing an N95-comparable or higher-level respirator and eye protection
      • Intermediate-risk: symptom monitoring is necessary; need for postexposure prophylaxis can be determined on an individual basis
        • Intermediate-risk exposures include:
          • Community settings:
            • Contact between an exposed person's intact skin and the skin lesions, bodily fluids, or potentially contaminated materials (eg, linens, clothing, sex toys) from a person with monkeypox or
            • Contact between an exposed person's sleeves or other clothing and the skin lesions, bodily fluids, or contaminated materials from a person with monkeypox
          • Health care settings:
            • Being within 6 feet for 3 hours or more (cumulative) of an unmasked patient with monkeypox without wearing at least a surgical mask or
            • Unprotected contact between an exposed person's intact skin and the skin lesions, bodily fluids, or potentially contaminated materials (eg, linens, clothing) from a patient with monkeypox or
            • Contact between an exposed person's sleeves or other clothing and the skin lesions, bodily fluids, or contaminated materials from a patient with monkeypox while not wearing a gown
      • Low-risk: symptom monitoring is recommended; postexposure prophylaxis is not indicated
        • Low-risk exposures include:
          • Community settings:
            • Entry into the living space of a person with monkeypox, in the absence of other exposures
          • Health care settings:
            • Entering the room or patient care area of a patient with monkeypox without all recommended personal protective equipment, in the absence of other exposures
      • No risk: neither symptom monitoring nor postexposure prophylaxis is indicated
        • No contact with the person with monkeypox or potentially contaminated materials, and no entry into their room or living space
• Preexposure prophylaxis
  • One vaccine, Jynneos, is licensed in the United States for the prevention of monkeypox and smallpox; another, ACAM2000, is licensed for the prevention of smallpox but is considered effective for the prevention of monkeypox as well; although there are not yet robust vaccine efficacy data for the current outbreak, efficacy is estimated to be over 85%, based on prior data from Africa, as well as immunologic and animal studies ^r24r79
  • Before the 2022 multi-country outbreak, the Advisory Committee on Immunization Practices (of CDC) recommended limited use of Jynneos or ACAM2000 for preexposure vaccination of certain laboratory and health care personnel at ongoing risk for occupational exposure to orthopoxviruses, including: ^r80
    • Research laboratory personnel
    • Clinical laboratory personnel performing diagnostic testing for orthopoxviruses
    • Designated response team members
    • Health care personnel who administer ACAM2000 or care for patients infected with orthopoxviruses
  • During the 2022 U.S. monkeypox outbreak, in jurisdictions with sufficient vaccine supply, CDC recommends that monkeypox preexposure prophylaxis be offered to those with the highest potential for monkeypox exposure, such as: ^r79
    • Gay, bisexual, or other men who have sex with men, transgender, or nonbinary people who within the past 6 months have received a diagnosis of one or more reportable sexually transmitted diseases or have had more than one sex partner
    • People who within the past 6 months have had sex at a commercial sex venue or in association with a large public event in an area with known monkeypox transmission
    • Sex partners of people with above risks
    • People who anticipate experiencing above risks
  • Vaccination for all front-line healthcare workers, or for the general public at large, is not recommended at this time ^r25
  • Vaccines for preexposure prophylactic vaccination can be obtained from CDC Drug Service after consultation with CDC Emergency Operations Center (telephone, 1-770-488-7100) ^r15
  • It is unclear how much protection against monkeypox is conferred by previous smallpox vaccination; CDC recommends following the same vaccination schedules as for those not previously vaccinated ^r79
• Postexposure prophylaxis
  • Vaccines are effective in preventing disease before monkeypox exposure, and it is believed that they may prevent or ameliorate disease after exposure as well ^r24
  • Recommended for postexposure prophylaxis in persons with high-risk exposures and can be considered on an individual basis for persons with intermediate-risk exposures ^r23
  • Vaccination within 4 days of exposure is recommended to prevent disease ^r24
  • Vaccination between 4 and 14 days after exposure may reduce disease severity but may not prevent disease ^r24
  • Vaccines for postexposure prophylaxis can be obtained from the Strategic National Stockpile via CDC; requests should be initiated through state or territorial health authorities, but CDC Emergency Operations Center (telephone, 1-770-488-7100) is available for consultations to assist with appropriate vaccine use ^r15
  • For the 2022 outbreak event, some public health jurisdictions are employing an expanded postexposure prophylaxis strategy (notated as PEP++), with vaccination offered to persons at increased risk of recent monkeypox exposure (even without confirmed exposure), including the following: ^r24r79
    • Known monkeypox contacts identified through case investigation, contact tracing, and risk exposure assessments
    • A sexual partner in the past 14 days diagnosed with monkeypox
    • Certain gay, bisexual, or other men who have sex with men, or transgender people who have sex with men, with any of the following in the past 14 days:
      • Sex with multiple partners
      • Sex at a commercial sex venue
      • Sex in association with an event, venue, or defined area with known monkeypox transmission
  • Current vaccination efforts in the 2022 outbreak response in the United States are primarily deploying Jynneos vaccine; any consideration of ACAM2000 should be made in consultation with CDC ^r79
  • Persons diagnosed with monkeypox during the current outbreak are believed to have immune protection, and at present CDC does not recommend vaccination in such persons ^r25
  • Other agents for postexposure prophylaxis ^r14r69
    • Although clinical efficacy is unknown, VIGIV and tecovirimat may be considered for use as monkeypox postexposure prophylaxis in certain limited circumstances if vaccines are contraindicated (eg, severe allergy to vaccine components)
    • Any such use must be in clinical consultation with CDC
• Vaccines
  • Jynneos ^r79r81r82
    • Approved for prevention of smallpox and monkeypox disease in patients aged 18 years or older who are determined to be at high risk for infection; FDA has issued an emergency use authorization for use in the prevention of monkeypox disease in patients younger than 18 years ^r70
    • Nonreplicating live virus (vaccinia) preparation
    • Completion of standard regimen requires 2 subcutaneous injections 4 weeks apart; vaccination is considered complete 2 weeks after the second dose ^r24
    • As a means of increasing available vaccine supply, an alternative regimen via intradermal administration may be used for patients aged 18 years or older under an FDA emergency use authorization; intradermal and subcutaneous routes of administration elicited similar immune responses in clinical studies ^r70r83
      • CDC states that when necessary, a person aged 18 years or older who received 1 Jynneos vaccine dose with the standard subcutaneous regimen may receive a second dose with the alternative intradermal regimen at the recommended interval to complete the series
      • Similarly, a person who has received 1 dose intradermally (alternative regimen) may receive the second dose subcutaneously (standard regimen) ^r25
    • Although some domestic and international jurisdictions are delaying the second dose, or employing a "1 dose only" strategy because of supply limitations, CDC states that 2 doses are required for most patients, as this is the only FDA-approved regimen ^r79
      • Recommended interval between the 2 doses of vaccine is at least 4 weeks; doses may be up to 5 weeks apart ^r82
        • If the second dose is not administered within the recommended interval, it should be administered as soon as possible; there is no need to restart the regimen or add doses if the dosing interval is extended ^r82
    • CDC is collecting data on Jynneos vaccine efficacy in the 2022 outbreak. Because of currently limited knowledge about the effectiveness of vaccines in this outbreak, people who are vaccinated should continue to take steps to protect themselves from infection by avoiding close, skin to skin contact with individuals who have monkeypox ^r79
      • Early data suggests that even 1 dose of Jynneos vaccine is protective against monkeypox infection; a recent study reporting on 5402 monkeypox cases occurring among males aged 14 to 49 years in the United States found that the average monkeypox incidence among unvaccinated persons was 14.3 times that among persons who had received 1 dose of Jynneos vaccine 14 or more days earlier ^r84
    • Preferred vaccine for most patients in whom vaccination is indicated, including patients with HIV, pregnant or breastfeeding patients, and pediatric patients ^r43r68r69
      • Elicited higher peak neutralizing antibody titers against smallpox compared with ACAM2000 in clinical trials, with better safety profile ^r85
      • Less potential for adverse events compared with ACAM2000 vaccine ^r24
      • Can be used in certain immunocompromised patients in whom ACAM2000 vaccine is contraindicated ^r85
    • Generally well-tolerated, with few adverse reactions noted in clinical studies ^r80
    • Warnings listed for severe allergic reactions (including anaphylaxis) and diminished response in immunocompromised patients
    • Preexposure prophylaxis ^r81
      • Subcutaneous
        • Modified Vaccinia Ankara Suspension for injection; Infants, Children, and Adolescents: 0.5 mL subcutaneously for 2 doses administered 4 weeks apart.
        • Modified Vaccinia Ankara Suspension for injection; Adults: 0.5 mL subcutaneously for 2 doses administered 4 weeks apart.
      • Intradermal
        • Modified Vaccinia Ankara Suspension for injection; Adults: 0.1 mL intradermally for 2 doses administered 4 weeks apart.
    • Postexposure prophylaxis ^r24r81
      • Subcutaneous
        • Modified Vaccinia Ankara Suspension for injection; Infants, Children, and Adolescents: 0.5 mL subcutaneously for 2 doses administered 4 weeks apart. Administer within 4 days from exposure date to prevent onset of disease. If administered between 4 and 14 days after exposure, vaccination may reduce symptoms of disease, but not prevent disease.
        • Modified Vaccinia Ankara Suspension for injection; Adults: 0.5 mL subcutaneously for 2 doses administered 4 weeks apart. Administer within 4 days from exposure date to prevent onset of disease. If administered between 4 and 14 days after exposure, vaccination may reduce symptoms of disease, but not prevent disease. If it has been more than 3 years since vaccination, consider revaccinating.
      • Intradermal
        • Modified Vaccinia Ankara Suspension for injection; Adults: 0.1 mL intradermally for 2 doses administered 4 weeks apart. Administer within 4 days from exposure date to prevent onset of disease. If administered between 4 and 14 days after exposure, vaccination may reduce symptoms of disease, but not prevent disease. If it has been more than 3 years since vaccination, consider revaccinating.
  • ACAM2000 ^r86
    • Approved for active immunization against smallpox disease in persons aged 16 years or older determined to be at high risk for infection
    • CDC-held EA-IND protocol allows use for non-smallpox orthopoxvirus infection (eg, monkeypox) during an outbreak ^r30
    • Live preparation of vaccinia inoculated directly into skin via percutaneous scarification
    • Results in a localized viral inoculation lesion; vaccinia can progress and spread in the vaccine recipient, and it can even be transmitted to close contacts and result in clinically significant infection
    • Greater potential for serious adverse events compared with Jynneos vaccine
    • Contraindicated in severe immunodeficiency, owing to possible severe localized or systemic vaccinia infection
    • Contraindicated in patients with HIV (regardless of immune status) and pregnant or breastfeeding patients; Jynneos vaccine is preferred in pediatric populations when vaccination is indicated ^r43r68r69
    • BLACK BOX WARNING for numerous rare complications potentially resulting in severe disability, permanent impairment, and death, including myocarditis and pericarditis, encephalitis, encephalopathy, progressive or generalized vaccinia, severe skin infections or reactions, ocular complications, blindness, and fetal death
    • Preexposure prophylaxis ^r86
      • Vaccinia Virus Strain New York City Board of Health Live Antigen Solution for percutaneous scarification; Adolescents 16 to 17 years: 0.0025 mL (a droplet of vaccine) administered percutaneously onto the arm by rapidly making 15 needle punctures. If a major reaction is not obtained 6 to 8 days after vaccination, check vaccination procedures, and repeat vaccination with vaccine from another vial or vaccine lot, if available. If a repeat vaccination using vaccine from another vial or vaccine lot fails to produce a major reaction, consult CDC or state or local health department before giving another vaccination. Patients who are at continued high risk of monkeypox exposure may be revaccinated every 3 years. For booster vaccination, make 15 needle punctures. There may be a reduced cutaneous response to revaccination; do not revaccinate.
      • Vaccinia Virus Strain New York City Board of Health Live Antigen Solution for percutaneous scarification; Adults: 0.0025 mL (a droplet of vaccine) administered percutaneously onto the arm by rapidly making 15 needle punctures. If a major reaction is not obtained 6 to 8 days after vaccination, check vaccination procedures, and repeat vaccination with vaccine from another vial or vaccine lot, if available. If a repeat vaccination using vaccine from another vial or vaccine lot fails to produce a major reaction, consult CDC or state or local health department before giving another vaccination. Patients who are at continued high risk of monkeypox exposure may be revaccinated every 3 years. For booster vaccination, make 15 needle punctures. There may be a reduced cutaneous response to revaccination; do not revaccinate.
    • Postexposure prophylaxis ^r24r86
      • Vaccinia Virus Strain New York City Board of Health Live Antigen Solution for percutaneous scarification; Adolescents 16 to 17 years: 0.0025 mL (a droplet of vaccine) administered percutaneously onto the arm by rapidly making 15 needle punctures. Administer within 4 days from exposure date to prevent onset of disease. If administered between 4 and 14 days after exposure, vaccination may reduce symptoms of disease, but not prevent disease. If it has been more than 3 years since vaccination, consider revaccinating. If a major reaction is not obtained 6 to 8 days after vaccination, check vaccination procedures, and repeat vaccination with vaccine from another vial or vaccine lot, if available. If a repeat vaccination using vaccine from another vial or vaccine lot fails to produce a major reaction, consult CDC or state or local health department before giving another vaccination. There may be a reduced cutaneous response to revaccination; do not revaccinate.
      • Vaccinia Virus Strain New York City Board of Health Live Antigen Solution for percutaneous scarification; Adults: 0.0025 mL (a droplet of vaccine) administered percutaneously onto the arm by rapidly making 15 needle punctures. Administer within 4 days from exposure date to prevent onset of disease. If administered between 4 and 14 days after exposure, vaccination may reduce symptoms of disease, but not prevent disease. If it has been more than 3 years since vaccination, consider revaccinating. If a major reaction is not obtained 6 to 8 days after vaccination, check vaccination procedures, and repeat vaccination with vaccine from another vial or vaccine lot, if available. If a repeat vaccination using vaccine from another vial or vaccine lot fails to produce a major reaction, consult CDC or state or local health department before giving another vaccination. There may be a reduced cutaneous response to revaccination; do not revaccinate.
  • WHO has also published interim guidance on vaccines and immunization for monkeypox, for international application; WHO and CDC recommendations are largely congruent ^r87