Mpox (Monkeypox)

Key Points

• Mpox (also known as monkeypox) is a zoonotic viral disease spread via direct contact, respiratory secretions, and contaminated materials and surfaces ^r1r2r3
• Mpox classically presents with rash, fever, lymphadenopathy, and a clinical course similar to that of smallpox but milder ^r1r4r5
• Mpox is caused by mpox virus (also known as monkeypox virus or sometimes MPXV), 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 ^r2
• In accordance with current best practices for naming infectious diseases and pathogens, in November 2022 WHO announced adoption of the new term "mpox" as a synonym for "monkeypox disease"; as of 2024, "mpox" is now the sole preferred term for the disease ^r6
• The naming of viruses is separate from that of diseases and is the responsibility of the International Committee on the Taxonomy of Viruses, which is currently working separately on the official renaming of all orthopoxvirus species including mpox; though this process is still underway, the use of the name "mpox" in reference to both the disease and the virus that causes it has become conventional ^r6
• Mpox is endemic in several African countries, and until 2022, nearly all reported cases arose in Africa, with rare sporadic cases elsewhere; from mid-2022 through 2023, there was a multicountry outbreak in nonendemic countries, including the United States, with atypical clinical features and most cases identified in men who have sex with men ^r1r7
  • WHO declared the 2022 multicountry outbreak a public health emergency of international concern in July 2022; US declared the outbreak to be a national public health emergency in August 2022
  • Case counts in the United States and worldwide steadily declined after August 2022; the US public health emergency declaration expired at the end of January 2023, while the WHO emergency declaration ended in May 2023 ^r7r8
  • Over 92,000 total cases of mpox worldwide associated with the 2022-2023 multicountry outbreak were reported to WHO, with over 31,000 cases in the United States ^r7r8
  • Daily new cases of mpox reported to CDC peaked in August 2022 at over 600 new cases daily and subsequently steadily declined, new cases are now sporadic and rare ^r8
• Mpox should be considered in a patient with appropriate clinical features (especially rash) and with epidemiologic risk factors for recent mpox exposure; close person to person contact, especially intimate and sexual contact, was identified as the primary mode of exposure in 2022-2023 outbreak–related cases ^r9r10
• Initial prodromal symptoms are nonspecific and may include fever, chills, malaise, headache, myalgia, respiratory symptoms, weakness, and lymphadenopathy; prodromal symptoms typically precede the appearance of rash, but these symptoms may be very mild, may be absent altogether, may be concurrent with rash, or may even develop after rash first appears ^r11r12r13r14
• Rash is invariably present in mpox, with skin lesions that are typically deep-seated, well demarcated, and umbilicated; initial lesions in mucosal regions (oral, genital, perianal) were most common in 2022-2023 outbreak–related cases ^r13r15
• Mpox is diagnosed via laboratory detection of mpox virus in the setting of appropriate epidemiologic risk factors and clinical findings
• Diagnostic testing for mpox should be undertaken in consultation with public health authorities and may consist of either generic orthopox or mpox-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 ^r12r16
• Differential diagnosis for mpox includes other, more common causes of localized genital lesions and rash; the overall clinical features of mpox are similar to those of smallpox, which has been eradicated worldwide
• Most patients with mpox 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 anatomical areas ^r17
• Currently there are no treatments approved specifically for mpox virus infection, but several antiviral agents originally developed for treatment of smallpox and other viral infections may be considered ^r17
• Tecovirimat is the antiviral treatment of choice for mpox disease; it can be accessed either through enrollment in the STOMP trial (Study of Tecovirimat for Human Monkeypox Virus) being conducted by the National Institute of Allergy and Infectious Diseases, or via the CDC's EA-IND protocol (expanded access–investigational new drug) allowing for use during an mpox outbreak ^r17r18
• 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
• Mpox 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 2022-2023 outbreak–related was substantially lower, at less than 0.2% ^r1r7
• 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 ^r19r20
• 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 ^r21r22
• One vaccine (Jynneos) is licensed in the United States for prevention of mpox and smallpox, and another (ACAM2000) is licensed for prevention of smallpox but considered effective for prevention of mpox as well; vaccination is recommended as preexposure prophylaxis for certain persons at ongoing significant risk for mpox exposure and can be used as postexposure prophylaxis for persons who have had recent confirmed or likely high-risk or intermediate-risk exposures ^r21r22
• When vaccination is indicated, Jynneos is the vaccine of choice for most patients and clinical circumstances; any consideration of ACAM2000 should be made in consultation with CDC ^r23
• CDC Emergency Operations Center (telephone, 1-770-488-7100) is available for consultation regarding appropriate utilization of medical countermeasures for mpox 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 mpox, particularly in patients with established high-risk epidemiologic features (ie, contact with someone with similar rash or confirmed mpox diagnosis, close contact with people in a social network with mpox activity, history of recent international travel to country with confirmed cases) ^r10r15
• Suspected mpox 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

• Mpox cases associated with the 2022-2023 outbreak event 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 ^r13
• Mpox 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 mpox and sexually transmitted diseases have been reported, and presence of a sexually transmitted infection does not preclude mpox ^r13

Clinical Clarification

• Mpox (previously known as monkeypox) is a zoonotic viral disease spread via direct contact, respiratory secretions, and contaminated materials and surfaces ^r1r2r3
• Mpox classically presents with rash, fever, lymphadenopathy, and a clinical course similar to that of smallpox but milder ^r1r4r5r24
• Mpox is caused by mpox virus (also known as monkeypox virus or sometimes MPXV), 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 ^r2r3
• The disease's original name reflected that the disease and virus were first detected in monkeys, but the natural host reservoir remains unknown, and rodents and other small mammals are most frequently implicated ^r2r3
• In accordance with current best practices for naming infectious diseases and pathogens, in November 2022 WHO announced adoption of the new term "mpox" as a synonym for "monkeypox disease"; as of 2024, "mpox" is now the sole preferred term for the disease ^r6
• The naming of viruses is separate from that of diseases and is the responsibility of the International Committee on the Taxonomy of Viruses, which is currently working separately on the official renaming of all orthopoxvirus species including mpox; though this process is still underway, the use of the name "mpox" in reference to both the disease and the virus that causes it has become conventional ^r6
• Mpox is endemic in several African countries, and until 2022, nearly all reported cases arose in Africa, with rare sporadic cases elsewhere; from mid-2022 through 2023, there was a multicountry outbreak in nonendemic countries, including the United States, with atypical clinical features and most cases identified in men who have sex with men ^r7
  • First known significant outbreak of mpox in the United States was in 2003, involving 47 confirmed and probable cases that were traced to infected pet prairie dogs; no more outbreaks occurred in the United States until 2022 ^r4r5
  • WHO declared the multicountry outbreak a public health emergency of international concern in July 2022; the United States declared the outbreak to be a national public health emergency in August 2022
  • Cases worldwide and in the United States steadily declined after August 2022; the US public health emergency declaration expired at the end of January 2023, while WHO emergency declaration ended in May 2023 ^r7r8r25
  • Over 92,000 total cases of mpox worldwide associated with the 2022-2023 multicountry outbreak were reported to WHO, with over 31,000 cases in the United States ^r7r26
  • Daily new cases of mpox reported to CDC peaked in August 2022 at over 600 new cases daily and subsequently steadily declined; new cases in the United States are now sporadic and rare ^r8
• Historical mpox case fatality rates of 3% to 6% were previously reported in African countries where the disease is endemic; the estimated case fatality rate associated with the 2022-2023 multicountry outbreak was substantially lower, at less than 0.2% ^r1r7

Classification

• CDC case definitions used for the 2022-2023 multicountry outbreak event ^r10
  • Suspect case
    • New rash characteristic of mpox or
    • Meets 1 epidemiologic criterion within 21 days of symptom onset and high clinical suspicion for mpox
  • 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
  • Confirmed case
    • Criteria met for suspect case and
    • Mpox infection confirmed by one of the following:
      • Detection of mpox virus DNA by polymerase chain reaction testing or next-generation sequencing of a clinical specimen or
      • Isolation of mpox virus in culture from a clinical specimen
  • Epidemiologic criteria
    • Contact with another case or cases with a similar rash or diagnosis of confirmed or probable mpox or
    • Close or intimate in-person contact with persons in a social network experiencing mpox activity, such as men who have sex with men or
    • Travel outside the United States to a country with confirmed mpox or where mpox virus is endemic or
    • Contact with a wild animal or exotic pet that is an African endemic species, or use of a product from such an animal
  • Exclusion criteria
    • Alternative diagnosis fully explains presentation or
    • Absence of rash within 5 days of illness onset or
    • High-quality clinical specimen does not demonstrate presence of orthopoxvirus, mpox virus, or orthopoxvirus antibodies
• WHO case definitions used for the 2022-2023 multicountry outbreak event were slightly different, as follows: ^r27
  • Suspected case
    • Known contact with probable or confirmed mpox case within 21 days of developing any of the following symptoms:
      • Acute onset of fever
      • Headache
      • Myalgia
      • Back pain
      • Lymphadenopathy
      • Profound weakness or fatigue
    • 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 mpox 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 4-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 mpox infection via real-time polymerase chain reaction or sequencing of mpox 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 mpox
• 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

Disposition

Treatment Options

Most patients with mpox have mild, self-limited disease, which can be managed with supportive care alone ^r17

• As rash is the defining feature of mpox disease, careful skin care and management of lesions is essential for all patients
• Other supportive care modalities are individualized based on patient symptoms and disease manifestations, and can include topical and oral medications as well as local treatments for symptomatic relief ^r60

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): ^r17

• 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 conditions affecting skin integrity, children, or pregnant or breastfeeding adults
• Patients with infection involving high-risk anatomical areas (eg, eyes, mouth, genitals, anus) with potential for serious adverse outcomes

High clinical suspicion is sufficient for consideration of treatment initiation ^r28

Topical ophthalmic antiviral treatment can be considered in consultation with an ophthalmologist for patients with eye involvement ^r61

Currently there are no treatments approved specifically for mpox virus infection, but several antiviral agents originally developed for treatment of smallpox and other viral infections may be considered; they may be 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 ^r17

• Tecovirimat ^r18r62
  • Approved for treatment of human smallpox disease in adults and children weighing at least 3 kg
  • Demonstrated efficacy against a diverse range of orthopoxviruses per in vitro and in vivo animal studies; efficacy data for treating mpox in humans is being collected ^r63
  • Antiviral agent of choice for treatment of mpox virus infections in people; other agents can be considered as alternative or additive therapy in special circumstances such as disease progression on tecovirimat, concern for tecovirimat resistance, tecovirimat intolerance, or contraindication to tecovirimat therapy ^r17
  • Patients eligible for treatment with tecovirimat should be informed of and consider voluntary enrollment in the STOMP trial (Study of Tecovirimat for Human Monkeypox Virus) being conducted by the National Institute of Allergy and Infectious Diseases to evaluate tecovirimat efficacy; all high-risk patients will be enrolled in an open-label arm and receive tecovirimat, while other adult participants will be randomized to tecovirimat or placebo ^r17r64
  • If participation in the STOMP trial is declined or otherwise infeasible, tecovirimat can also be accessed via the CDC's EA-IND protocol (expanded access–investigational new drug), allowing tecovirimat use in treatment of mpox during an outbreak ^r65
  • Instructions on obtaining and using tecovirimat (via the STOMP trial or the CDC's EA-IND protocol), as well as required forms, are available at the CDC website ^r18r64
    • 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 mpox under its EA-IND protocol ^r64
      • 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
    • "Patient's Guide to Mpox Treatment with Tecovirimat (TPOXX)" is also available at the CDC website ^r66
  • Available in capsule and injection form
  • Injection is generally contraindicated in severe renal impairment; exceptions may be considered if enteral administration is not anticipated to be dependable or feasible, based on individual patient risk-benefit assessment by the treating clinician that determines IV tecovirimat clinically necessary in consultation with CDC ^r65
  • A report on clinical use of tecovirimat for treatment of mpox 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 ^r67
• Cidofovir ^r68
  • Originally approved for treatment of cytomegalovirus in patients with AIDS; has been used for other viral infections
  • Demonstrated efficacy against a diverse range of orthopoxviruses per in vitro and in vivo animal studies; efficacy data for treating mpox in humans is unavailable
  • CDC has an EA-IND protocol that allows use in treatment of mpox in an outbreak
  • IV infusion; must be administered with probenecid
  • Brincidofovir is a prodrug of cidofovir; brincidofovir and cidofovir should not be administered concurrently
  • BOXED WARNING 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) ^r69
  • Approved for treatment of complications due to vaccinia vaccination
  • Efficacy data for treating mpox in humans is unavailable
  • CDC has an EA-IND protocol that allows use in treatment of mpox in an outbreak; VIGIV is available upon clinician request to CDC on an individual basis
  • Can be considered for prophylactic use after mpox exposure if smallpox or mpox vaccination is contraindicated
  • For IV use only
  • BOXED 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 ^r70
  • Approved for treatment of human smallpox disease in adults and children, including neonates
  • Demonstrated efficacy against a diverse range of orthopoxviruses per in vitro and in vivo animal studies; efficacy data for treating mpox in humans is unavailable
  • Available from Strategic National Stockpile upon receipt of an FDA-authorized single-patient emergency use IND
  • Available in tablet and oral suspension form
  • Brincidofovir is a prodrug of cidofovir and may have an improved safety profile; brincidofovir and cidofovir should not be administered concurrently
  • BOXED WARNING for increased mortality risk when used for prolonged durations
  • No contraindications noted in prescribing information
• Trifluridine ^r71
  • 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 ^r32
  • May be considered for use in patients with ocular mpox involvement in consultation with an ophthalmologist; prophylactic use can be considered for patients with eye-adjacent lesions ^r61
  • For topical ophthalmic use only
  • Contraindicated in patients who develop hypersensitivity reactions or chemical intolerance to trifluridine

Complications

• Pitted scarring (pockmarks) is the most common long-term sequela for survivors ^r34
• Ocular infections can result in corneal scarring and permanent vision loss ^r34
• Oral lesions and regional lymphadenopathy can lead to difficulties with swallowing and thus with eating and drinking ^r34
• Vomiting and diarrhea can result in severe dehydration ^r34
• Perianal lesions can lead to severe pain, tenesmus, and bleeding ^r32
• Secondary bacterial infections of skin ^r34
• Secondary infections of lungs can result in bronchopneumonia and respiratory distress, potentially requiring intubation ^r34
• Neurologic complications include encephalitis and transverse myelitis ^r34r57
• Cardiac complications include myocarditis and pericardial disease ^r57
• Urologic complications include urethritis and penile necrosis ^r57
• Rheumatologic complications include arthritis and synovitis ^r28
• Obstructions (eg, in the lungs or gastrointestinal tract), can occur secondary to strictures, lymphadenopathy, and edema ^r28
• Septicemia ^r34
• Hemodynamic instability may require vasopressor support ^r57
• Death

Prognosis

• Mpox has a mild, self-limited course for most patients ^r4r5r32
• Mpox 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 2022-2023 multicountry outbreak was substantially lower, at less than 0.2% ^r4r5r7
• Mortality is higher in children and young adults; disease is more severe in persons with immunocompromise, most notably HIV ^r3r57
  • A global case series found higher mpox mortality in patients whose HIV disease was substantially impairing immunity (eg, CD4 count less than 200 cells/mm³) ^r80
• A total of 38 mpox-associated deaths in the United States were reported to CDC between May 10, 2022 and March 7, 2023; of the decedents, 87% were Black, 95% were cisgender men, and nearly all with known HIV status were HIV-positive (31 of 33: 94%) ^r91
  • Of 24 persons with HIV for whom such data were available, all had advanced HIV, typically with CD4 count less than 50 cells/mm³

Prevention

• General infection control measures ^r92r93
  • Avoid close, skin to skin contact, including intimate or sexual contact, with anyone that has an mpox-like rash ^r47
  • 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
  • Adhere to appropriate hand hygiene
  • Use appropriate personal protective equipment when caring for patients or collecting specimens for diagnosis
  • Vaccinate those at increased risk
• Infection control in home settings ^r20
  • 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 ^r94
    • 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 mpox ^r94
  • Sexual activity
    • Patients should refrain from all sexual activity during the isolation period
    • Barrier practices (eg, condoms) are recommended after recovery; data to guide duration are sparse, but some countries recommend at least 8 weeks
  • Isolating with animals in the home ^r20r95
    • Patients with mpox should avoid contact with mammals, including pets
    • Potentially contaminated materials should be kept away from domestic animals (eg, bandages, linens, laundry)
  • 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 ^r48
• Infection control in health care settings ^r19
  • Regarding prevention of mpox transmission in health care settings, CDC references 2007 guidelines for preventing transmission of infectious agents in these settings ^r96
  • Patients with suspected or confirmed mpox 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 well-being
  • 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 ^r97
  • 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 mpox 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 mpox infection; consultation with local or state health department might be necessary, depending on locale ^r48
• Safer sex practices
  • Male to male intimate and sexual contact between gay, bisexual, and other men who have sex with men was the primary mode of transmission in 2022-2023 outbreak–related cases; various harm reduction efforts focused on safer sex practices in these populations ^r7
  • During the outbreak, CDC issued recommendations for safer sexual practices to help reduce the risk of mpox exposure and transmission, including: ^r46
    • Deferring potential high-risk sexual behaviors, until completion of vaccination for mpox
    • Limiting number of sexual partners
    • Exchanging contact information with new 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
    • Avoiding intimate activity if new or unexplained rash or other symptoms present, until evaluated by a health care practitioner and mpox is ruled out
• Exposure management
  • Exposures in the community ^r22
    • Confer with appropriate public health authorities when monitoring of exposed contacts is undertaken ^r13
    • Exposure risk assessment should be performed to determine possible need for postexposure prophylaxis
    • Contacts with confirmed mpox 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 mpox 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 ^r19
    • Notify hospital infection control when monitoring of exposed patients is undertaken
    • Asymptomatic exposed patients do not need to be isolated, but they 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 mpox 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 mpox until rash is evaluated and mpox has been ruled out
    • If other symptoms develop during the monitoring period, the patient should be placed on empiric isolation precautions for mpox 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 ^r19
    • 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 mpox 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 mpox 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 ^r19r22
    • Exposure risk assessment for all persons with potential mpox 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 Jynneos or ACAM2000 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 mpox or
            • Any sexual or intimate contact involving the mucous membranes of a person with mpox
          • 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 mpox or
            • Being inside the patient's room or within 6 feet of a patient with mpox 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:
            • Being within 6 feet for 3 hours or more (cumulative) of an unmasked person with mpox without wearing at least a surgical mask or
            • 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 mpox or
            • Contact between an exposed person's clothing and the skin lesions, bodily fluids, or contaminated materials from a person with mpox
          • Health care settings:
            • Being within 6 feet for 3 hours or more (cumulative) of an unmasked patient with mpox 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 mpox or
            • Contact between an exposed person's clothing and the skin lesions, bodily fluids, or contaminated materials from a patient with mpox 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 mpox, in the absence of other exposures
          • Health care settings:
            • Entering the room or patient care area of a patient with mpox 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 mpox 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 mpox and smallpox, while another, ACAM2000, is licensed for the prevention of smallpox but is considered effective for the prevention of mpox as well; although efficacy data is still being collected for the 2022-2023 outbreak response, vaccine efficacy was initially predicted to be over 85%, based on prior data from Africa, as well as immunologic and animal studies ^r21
  • CDC recommends that mpox vaccination be offered to: ^r21r23
    • Gay, bisexual, or other men who have sex with men, transgender people, or nonbinary people who within the past 6 months have had more than one sex partner or have received a diagnosis of one or more reportable sexually transmitted diseases
    • 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 mpox transmission
    • People who anticipate experiencing above risks
    • Sex partners of people with above risks
    • People with HIV or other causes of immunosuppression with recent or potential mpox exposure
    • People with increased risk of occupational exposure to mpox, such as persons who work with orthopoxviruses in a laboratory
  • Vaccination for all frontline healthcare workers, or for the general public at large, is not recommended
  • Vaccines for preexposure prophylactic vaccination can be obtained from CDC Drug Service after consultation with CDC Emergency Operations Center (telephone, 1-770-488-7100) ^r13
  • If not locally available, vaccines for preexposure prophylaxis can be obtained from the Strategic National Stockpile; 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 ^r21
  • It is unclear how much protection against mpox is conferred by previous smallpox vaccination; CDC recommends following the same vaccination schedules as for those not previously vaccinated ^r21
• Postexposure prophylaxis
  • Vaccines are effective in preventing disease before mpox exposure, and it is believed that they may prevent or ameliorate disease after exposure as well ^r21
  • Recommended for postexposure prophylaxis in persons with high-risk exposures and can be considered on an individual basis for persons with intermediate-risk exposures ^r22
  • Vaccination within 4 days of exposure is recommended to prevent disease ^r21
  • Vaccination between 4 and 14 days after exposure may reduce disease severity but may not prevent disease ^r21
  • If not locally available, vaccines for postexposure prophylaxis can be obtained from the Strategic National Stockpile; 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 ^r13
  • As part of the 2022-2023 outbreak response, some public health jurisdictions employed an expanded postexposure prophylaxis strategy (notated as PEP++), with vaccination offered to persons at increased risk of recent mpox exposure (even without confirmed exposure), including the following: ^r21
    • Known mpox contacts identified through case investigation, contact tracing, and risk exposure assessments
    • A sexual partner in the past 14 days diagnosed with mpox
    • Certain gay, bisexual, or other men who have sex with men, or transgender or nonbinary 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 mpox transmission
  • Persons diagnosed with mpox during the 2022-2023 outbreak are believed to have immune protection, and at present CDC does not recommend vaccination in such persons
  • Other agents for postexposure prophylaxis ^r12r17r42
    • Although clinical efficacy is unknown, VIGIV and tecovirimat may be considered for use as mpox 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 ^r21r98
    • Approved for prevention of smallpox and mpox 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 mpox disease in patients younger than 18 years ^r86
    • 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 ^r21
      • Recommended interval between the 2 doses of vaccine is 4 weeks apart, but may be up to 5 weeks apart, based on available clinical study data
      • 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
    • 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 ^r21r86r99
      • 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)
      • Patients younger than 18 years and patients of any age with history of developing keloid scars should receive Jynneos by standard subcutaneous administration, rather than the intradermal route
      • Preliminary evidence indicates efficacy is comparable between standard subcutaneous and intradermal administration of Jynneos vaccine ^r100
    • CDC is collecting data on Jynneos vaccine efficacy ^r21
      • Estimates of vaccine effectiveness in US-based studies range from 36% to 75% for 1 dose and 66% to 89% for 2 doses
    • Preferred vaccine for most patients in whom vaccination is indicated, including patients with HIV, pregnant or breastfeeding patients, and pediatric patients ^r42r50r83
      • Elicited higher peak neutralizing antibody titers against smallpox compared with ACAM2000 in clinical trials, with better safety profile ^r101
      • Less potential for adverse events compared with ACAM2000 vaccine ^r21
      • Can be used in certain immunocompromised patients in whom ACAM2000 vaccine is contraindicated ^r101
    • Generally well tolerated, with few adverse reactions noted in clinical studies ^r102
    • Contraindicated in patients with history of severe allergic reaction after previous dose of Jynneos; caution is advised in patients with active moderate or severe acute illness, patients with history of severe allergic reaction to gentamicin or ciprofloxacin, and patients with history of severe allergic reaction to chicken or egg products
    • Preexposure prophylaxis ^r98
      • 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 ^r21r98
      • Subcutaneous
        • Modified Vaccinia Ankara Suspension for injection; Infants younger than 6 months: 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; Infants, Children, and Adolescents 6 months to 17 years: 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 ^r103
    • 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, mpox) during an outbreak ^r32
    • Jynneos vaccine is preferred for most patients and clinical circumstances; any consideration of ACAM2000 should be made in consultation with CDC ^r21
    • Live preparation of vaccinia inoculated directly into skin via percutaneous scarification
    • Vaccination is considered complete 4 weeks after dose administered
    • 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
    • Significantly greater potential for serious adverse events compared with Jynneos vaccine
    • Contraindicated in the following patients: ^r21
      • Those with:
        • History of severe allergic reaction after previous dose of ACAM2000
        • 3 or more major cardiac risk factors (eg, hypertension, diabetes, hyperlipidemia, family history of early-onset heart disease, smoking history)
        • Ocular disease treated with steroids
        • Congenital or acquired immunodeficiency, including HIV (regardless of immune status)
        • Atopic dermatitis, eczema, or other acute or exfoliative skin conditions
      • Pregnant or breastfeeding patients
      • Infants younger than 12 months
    • Caution is advised in patients with history of severe allergic reaction after neomycin or polymyxin B, patients with ongoing moderate or severe illness, and patients aged between 1 and 16 years
    • BOXED 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 ^r103
      • Vaccinia Virus Strain New York City Board of Health Live Antigen Solution for percutaneous scarification; Adolescents 16 and 17 years: 0.0025 mL 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. Patients who are at continued high risk of mpox 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 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. Patients who are at continued high risk of mpox 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 ^r21r103
      • Vaccinia Virus Strain New York City Board of Health Live Antigen Solution for percutaneous scarification; Adolescents 16 and 17 years: 0.0025 mL 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. 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 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. There may be a reduced cutaneous response to revaccination; do not revaccinate.
  • WHO has also published guidance on vaccines and immunization for mpox, for international application ^r104