Key Points

• Monkeypox is a zoonotic viral disease spread via direct contact, respiratory secretions, and contaminated materials and surfaces ^r1r2r3r4
• 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 ^r3
• Monkeypox classically presents with rash, fever, lymphadenopathy, and a clinical course similar to that of smallpox but milder; case fatality rates of 3% to 6% have been reported in African countries where the disease is endemic, but cases detected in the United States have not resulted in any deaths to date ^r2r5r6
• 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 ^r7
  • US has declared the ongoing 2022 multi-country outbreak a public health emergency; CDC provides frequent updates online regarding the domestic outbreak situation ^r8
  • 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
• Monkeypox should be considered in a patient with appropriate clinical features, especially rash, and potential exposure to monkeypox virus via contact with high-risk people, animals, or animal products, or travel to high-risk countries ^r10
• 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 ^r11r12r13r14
• 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 ^r14r15
• 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 ^r11r16
• 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 ^r17
• 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 ^r18
• 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 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 select laboratory and health care personnel at ongoing risk for occupational exposure and can be used as postexposure prophylaxis for persons who have had high-risk or intermediate-risk exposures ^r17r21r22
• For the 2022 outbreak, some public health jurisdictions are employing an expanded approach to postexposure prophylaxis, offering vaccination to individuals at increased risk of recent monkeypox exposure, even without documented exposure to someone with confirmed monkeypox ^r23
• 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) ^r10r15
• 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 ^r14
• 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 ^r14r24

Clinical Clarification

• Monkeypox is a zoonotic viral disease spread via direct contact, respiratory secretions, and contaminated materials and surfaces ^r1r2r3r4
• 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 ^r1r3r4
• 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 ^r1r3r4
• Monkeypox classically presents with rash, fever, lymphadenopathy, and a clinical course similar to that of smallpox but milder; case fatality rates of 3% to 6% have been reported in African countries where the disease is endemic, but cases detected in the United States have not resulted in any deaths to date ^r2r5r6r7
• 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 ^r7r25
  • 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 ^r8
  • 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

Classification

• CDC case definitions: ^r10
  • 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 ^r14
  • 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: ^r26
  • Suspected case
    • Unexplained acute rash or skin lesions in a person of any age and
    • One or more of the following:
      • Headache
      • Acute onset of fever
      • Lymphadenopathy
      • Myalgia
      • Back pain
      • Profound weakness
    • And other common causes of acute rash deemed incompatible with the clinical presentation
  • Probable case
    • Criteria met for suspected case and
    • One or more of the following:
      • Confirmed epidemiologic connection to a probable or confirmed monkeypox case within 21 days of symptom onset, via face to face exposure, direct physical contact, or contact with contaminated materials
      • Multiple or anonymous 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 (up to day 5-7) and convalescent (after day 21) samples, in the absence of other known orthopoxvirus exposure (eg, via smallpox vaccination)
      • Confirmed orthopoxvirus infection (eg, via PCR or sequencing)
  • Confirmed case
    • Criteria met for suspected or probable case and
    • Laboratory confirmation of monkeypox virus DNA via real-time polymerase chain reaction or sequencing

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
• Management of symptoms depending on affected systems or specific syndromes
• Antiviral treatment to ameliorate severe disease and reduce risk for patients with high risk of severe disease or high-risk disease features

Disposition

Treatment Options

Most patients with monkeypox have mild, self-limited disease, which can be managed with supportive care alone ^r18

Potential management options depend on affected systems and specific disease manifestations or complications; options may include the following: ^r41

• 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
• Mucosal lesions
  • Mucosal care and analgesic medications
• Vomiting/diarrhea
  • Oral or IV hydration and antiemetic/antidiarrheal medications
• Fever
  • Antipyretic medications and external cooling measures
• Skin compromise
  • Cleaning, moist dressings, topical antibiotics, surgical debridement, skin grafts
• Secondary skin infection
  • Antibiotics, incision and drainage, advanced wound management
• Inflammation/lymphadenopathy
  • Antiinflammatory and analgesic medications
• Ocular infection
  • Ophthalmic antibiotics, antivirals, and corticosteroids; comprehensive ophthalmic evaluation including slitlamp examination

Consider antiviral treatment for the following patients after consultation with state health authorities or CDC through the Emergency Operations Center (telephone, 1-770-488-7100): ^r18

• Patients with severe disease
• Patients at high risk of severe disease, such as those with significant immunocompromise or certain preexisting skin conditions, children, pregnant or breastfeeding adults, or those with significant disease-related complications
• Patients with infection involving high-risk anatomic areas (eg, eyes, mouth, genitals, anus)

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 is lacking owing to infeasibility of human smallpox experimentation ^r17r18

• Tecovirimat ^r42
  • 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 ^r43
  • CDC has an EA-IND protocol (expanded access–investigational new drug) that allows use in treatment of monkeypox in an outbreak
  • Instructions on obtaining and using tecovirimat, as well as required forms, are available at the CDC website ^r44
  • Available in capsule and injection form
  • Injection is contraindicated in severe renal impairment
• Cidofovir ^r45
  • 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) ^r46
  • 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 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 ^r47
  • 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

Complications

• Pitted scarring (pockmarks) is the most common long-term sequela for survivors ^r29
• Oral lesions and regional lymphadenopathy can lead to difficulties with swallowing and thus with eating and drinking ^r29
• Perianal lesions can lead to severe pain, tenesmus, and bleeding ^r27
• Secondary bacterial infections of skin ^r29
• Secondary infections of lungs, resulting in bronchopneumonia and respiratory distress ^r29
• Vomiting and diarrhea, resulting in severe dehydration ^r29
• Encephalitis ^r29
• Septicemia ^r29
• Ocular infections, which can result in corneal scarring and permanent vision loss ^r29

Prognosis

• Monkeypox has a mild, self-limited course for most patients ^r5r6r27
• Case fatality rates of 3% to 6% have been reported in African countries where the disease is endemic; 2022 outbreak cases in nonendemic countries have thus far resulted in relatively few deaths, with none in the United States ^r5r6r9
• Mortality is higher in children and young adults; disease is more severe in persons with immunocompromise ^r1

Prevention

• General infection control measures ^r55r56
  • Avoid close, skin-to-skin contact, including intimate or sexual contact, with anyone that has a monkeypox-like rash ^r35
  • 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 health care settings ^r20
  • Regarding prevention of monkeypox transmission in health care settings, CDC references 2007 guidelines for preventing transmission of infectious agents in these settings ^r57
  • 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 ^r58
  • 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 all lesions have scabbed off, separated, and healed with a fresh layer of intact skin, or until cleared by public health authorities ^r33
• Infection control in home settings ^r19
  • 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
    • Potentially contaminated personal items, such as clothing, linens, towels, dishes, and 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 interim guidance for household disinfection of monkeypox ^r59
  • Sexual activity
    • Patients should refrain from all sexual activity during the isolation period ^r24
    • Barrier practices (eg, condoms) are recommended after recovery; data to guide duration are sparse, but some countries recommend at least 8 weeks ^r24
  • 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 ^r33
• Exposure management
  • Monitoring people who have been exposed ^r21
    • Notify public health authorities when monitoring of exposed contacts is undertaken ^r14
    • Exposure risk assessment should be performed to determine possible need for postexposure prophylaxis
    • People with confirmed exposure to monkeypox should monitor for the following symptoms for 21 days after last exposure:
      • Fever of 38 °C or higher
      • Chills
      • New lymphadenopathy
      • New rash
    • 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 fever or rash develop, contacts should self-isolate and contact their local or state health department for further instructions
    • If chills or lymphadenopathy develop, contacts should isolate at home for 24 hours and monitor for emergence of fever or rash; the health department should be contacted for further instructions if these develop
  • Monitoring exposed health care professionals ^r21
    • Public health authorities should be notified when monitoring is undertaken of health care personnel; infection control can facilitate necessary reporting in the hospital setting ^r14
    • Exposure risk assessment should be performed to determine possible need for postexposure prophylaxis
    • Any health care workers who have cared for patients with monkeypox should monitor for possible symptoms of monkeypox, especially within 21 days of contact
    • Health care workers with unprotected exposures may continue to work, but they should measure temperatures at least twice daily for 21 days after exposure and be assessed for new fever or rash before work each day during this period
  • Exposure risk assessment and postexposure prophylaxis ^r21
    • 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; postexposure prophylaxis with ACAM2000 or Jynneos vaccination is recommended
        • High-risk exposures include:
          • Unprotected contact between a person's skin or mucous membranes and the skin, lesions, bodily fluids, or contaminated materials from a patient or
          • Being inside the patient's room or within 6 feet of a patient during aerosol-generating procedures without wearing an N95-comparable or higher-level respirator and eye protection or
          • Other exposures determined by public health authorities to be at this level
      • Intermediate-risk: symptom monitoring; need for postexposure prophylaxis can be determined on an individual basis
        • Intermediate-risk exposures include:
          • Being within 6 feet for 3 hours or more of an unmasked patient without wearing at least a surgical mask or
          • Contact between sleeves or other clothing and the patient's skin, lesions, bodily fluids, or contaminated materials or
          • Other exposures determined by public health authorities to be at this level
      • Low/uncertain-risk: symptom monitoring recommended; postexposure prophylaxis not indicated
        • Low/uncertain-risk exposures include:
          • Entering the patient's room without eye protection regardless of duration or
          • Gown, gloves, eye protection, and at least surgical mask worn for all entries into the patient's room or
          • Being within 6 feet of an unmasked patient for less than 3 hours without wearing at least a surgical mask or
          • Other exposures determined by public health authorities to be at this level
      • No risk: neither symptom monitoring nor postexposure prophylaxis indicated
        • These are exposures determined by public health authorities as not meeting criteria for other categories
• 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 ^r22r23
  • Advisory Committee on Immunization Practices (of CDC) has recommended use of Jynneos or ACAM2000 for preexposure vaccination of certain laboratory and health care personnel at ongoing risk for occupational exposure to orthopoxviruses, including: ^r60
    • 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 for patients infected with orthopoxviruses
  • Vaccines for preexposure prophylactic vaccination can be obtained from CDC Drug Service after consultation with CDC Emergency Operations Center (telephone, 1-770-488-7100) ^r14
  • 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 ^r23
• 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 ^r22
  • Recommended for postexposure prophylaxis in persons with high-risk exposures and can be considered on an individual basis for persons with intermediate-risk exposures ^r21
  • Vaccination within 4 days of exposure is recommended to prevent disease ^r22
  • Vaccination between 4 and 14 days after exposure may reduce disease severity but may not prevent disease ^r22
  • 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 ^r14
  • For the 2022 outbreak event, some public health jurisdictions are employing an expanded approach to postexposure prophylaxis, offering vaccination to individuals at increased risk of recent monkeypox exposure, even without documented exposure to someone with confirmed monkeypox ^r22r23
  • 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 ^r23
  • CDC is currently allocating Jynneos vaccine to public health jurisdictions for use in: ^r23
    • Known monkeypox contacts identified through case investigation, contact tracing, and risk exposure assessments
    • Presumed monkeypox contacts with:
      • A sexual partner in the past 14 days diagnosed with monkeypox
      • Multiple sexual partners in the past 14 days in a jurisdiction with known monkeypox
  • Other agents for postexposure prophylaxis ^r11r53
    • Though 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 ^r23r61
    • 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 ^r54
    • 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 ^r22
    • 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 ^r54r62
      • 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
    • 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 ^r23
      • Recommended interval between the 2 doses of vaccine is at least 4 weeks; doses may be up to 5 weeks apart ^r63
        • 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 ^r63
    • CDC is collecting data on Jynneos vaccine efficacy in the 2022 outbreak
    • Preferred vaccine for most patients in whom vaccination is indicated, including patients with HIV, pregnant or breastfeeding patients, and pediatric patients ^r37r52r53
      • Elicited higher peak neutralizing antibody titers against smallpox compared with ACAM2000 in clinical trials, with better safety profile ^r64
      • Less potential for adverse events compared with ACAM2000 vaccine ^r22
      • Can be used in certain immunocompromised patients in whom ACAM2000 vaccine is contraindicated ^r64
    • Generally well-tolerated, with few adverse reactions noted in clinical studies ^r60
    • Warnings listed for severe allergic reactions (including anaphylaxis) and diminished response in immunocompromised patients
    • Preexposure prophylaxis ^r61
      • 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 ^r22r61
      • 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 ^r65
    • 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 ^r27
    • 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 ^r37r52r53
    • 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 ^r65
      • 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 ^r22r65
      • 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 ^r66