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Mpox (Monkeypox)

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Sep.27.2023

Mpox (Monkeypox)

Synopsis

Key Points

  • Mpox (also known as monkeypox) is a zoonotic viral disease spread via direct contact, respiratory secretions, and contaminated materials and surfaces r1r2r3r4
  • Mpox classically presents with rash, fever, lymphadenopathy, and a clinical course similar to that of smallpox but milder r3r5r6
  • 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 r4
  • 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 synonymous name for the disease; both names will be used simultaneously for a transition period of 1 year, after which "mpox" will become the preferred term r7
  • 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 r7
  • Mpox 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 r3r8
    • WHO declared the 2022 multi-country 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 have steadily declined since August 2022; the US public health emergency declaration expired at the end of January 2023, while the WHO emergency declaration ended in May 2023 r8r9
    • Over 88,000 total cases of mpox worldwide associated with the 2022-2023 multi-country outbreak have been reported to WHO, with over 30,000 cases in the United States r8r9
    • Daily new cases of mpox reported to CDC peaked in August 2022 at over 600 new cases daily and subsequently steadily declined, with daily new cases in 2023 now in the single digits r9
  • Mpox should be considered in a patient with appropriate clinical features, especially rash, and epidemiologic risk factors for recent mpox exposure; close person to person contact, especially intimate and sexual contact, has been identified as the primary mode of exposure in 2022-2023 outbreak–related cases r10r11
  • 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 2022-2023 outbreak–related cases these symptoms may be very mild, may be absent altogether, may be concurrent with rash, or may even develop after rash first appears r12r13r14r15
  • 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) have been common in 2022-2023 outbreak–related cases r15r16
  • 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 r13r17
  • 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 r18
  • 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 r18
  • 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 r18r19
  • 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 has been substantially lower, at less than 0.2% r3r8
  • 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 r20r21
  • 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 r22r23
  • 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 r22r23
  • 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) r11r16
  • 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 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
  • 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 r15r24

Terminology

Clinical Clarification

  • Mpox (also known as monkeypox) is a zoonotic viral disease spread via direct contact, respiratory secretions, and contaminated materials and surfaces r1r2r3r4
  • Mpox classically presents with rash, fever, lymphadenopathy, and a clinical course similar to that of smallpox but milder r3r5r6r25
  • 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 r1r2r4
  • 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 r1r2r4
  • 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"; both names can be used simultaneously for a transition period of 1 year, after which "mpox" will become the preferred term r7
  • 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 r7
  • Mpox is endemic in several African countries, and until 2022, nearly all reported cases arose in Africa, with rare sporadic cases elsewhere; in May 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 r8
    • 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 r5r6
    • WHO declared the multi-country 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 have steadily declined since August 2022; the US public health emergency declaration expired at the end of January 2023, while WHO emergency declaration ended in May 2023 r8r9r26
    • Over 88,000 total cases of mpox worldwide associated with the 2022-2023 multi-country outbreak have been reported to WHO, with over 30,000 cases in the United States r8r27
    • Daily new cases of mpox reported to CDC peaked in August 2022 at over 600 new cases daily and subsequently steadily declined, with daily new cases in 2023 now in the single digits r9
  • 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 multi-country outbreak has been substantially lower, at less than 0.2% r3r8

Classification

  • CDC case definitions r11
    • 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
      • CDC has stated that for 2022-2023 outbreak–related cases, all confirmed orthopoxvirus infection cases in the United States are presumed to be mpox unless proven otherwise r15
    • 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
  • WHO case definitions for the 2022-2023 multi-country outbreak event are slightly different, as follows: r28
    • 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

Diagnosis

Clinical Presentation

History

  • Mpox should be considered in a patient with appropriate clinical features (especially rash) and epidemiologic risk factors for recent mpox exposure. Close person to person contact, especially intimate and sexual contact, has been identified as the primary mode of exposure in 2022-2023 outbreak–related cases r11
  • Epidemiologic history
    • Collect a complete sexual, social, and travel history for the past 21 days r29
    • Presence of one of the following high-risk epidemiologic features within 21 days of illness, in conjunction with clinical suspicion, can establish a suspect case of mpox per CDC case definitions: r11
      • 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
  • Clinical history r12r14
    • Incubation period ranges from 3 to 17 days; patients may be asymptomatic during this time r24
    • Emerging evidence suggests that mpox can be spread to others during the incubation period, 1 to 4 days before appearance of symptoms r14r30
    • Initial prodromal symptoms are nonspecific and may include fever, chills, malaise, headache, myalgia, respiratory symptoms, weakness, and lymphadenopathy; patients may be contagious during this period
    • Although prodromal symptoms preceding rash are typical of classic endemic mpox, atypical clinical presentations are common in 2022-2023 outbreak–related cases; these symptoms may be very mild, may be absent altogether, may be concurrent with rash, or may even develop after rash first appears r12r13r14r15
      • Of 2022-2023 outbreak–related cases reported to CDC, aside from rash, the symptoms reported most frequently during the course of illness are fever (67%), malaise (65%), chills (62%), pruritus (60%), lymphadenopathy (57%), headache (58%), and myalgia (56%) r31
    • Rash is invariably present in mpox infection; absence of rash within 5 days of illness onset rules out mpox r11
      • Rash typically develops within several days of fever, but it can also be the initial symptom, without fever or other prodromal symptoms, or even be the only apparent symptom of infection r12r14r15
      • Although initial rash on the face or in the oral cavity is commonly described in classic endemic mpox, initial rash in mucosal regions (oral, anal, genital) is more typical of 2022-2023 outbreak–related cases r32r33
      • Classic endemic mpox lesions tend to develop and evolve together on any given part of body (such as face or genitals); asynchronous evolution has been noted in 2022-2023 outbreak–related cases r32r34
      • Lesions evolve through macular, papular, vesicular, and pustular morphologies before scabbing over and resolving
      • Lesions can be extremely painful until they heal
      • Patients are contagious until all lesions have scabbed over and healed with a fresh layer of intact skin
    • Rectal symptoms can result from perianal lesions; these can be severe and can be the presenting concerns, particularly if lesions elsewhere are not readily visible r32r33
      • Of 2022-2023 outbreak–related cases reported to CDC, the most frequently reported rectal symptoms include rectal pain (41%), rectal bleeding (23%), tenesmus (20%), pus or blood in the stool (19%), and proctitis (16%) r31
    • Clinical course is similar to that of smallpox, but familiarity with smallpox has waned in era of vaccination and subsequent smallpox eradication r24
    • Overall course of illness is typically 2 to 4 weeks r12

Physical examination

  • Fever
    • Temperature is often between 38.5 and 40.5 °C r35
    • Very common in classic endemic mpox; present in 67% of 2022-2023 outbreak–related cases reported to CDC r13r31
  • Lymphadenopathy r12
    • Very common (90% of cases) in classic endemic mpox; present in 57% of 2022-2023 outbreak–related cases reported to CDC r1r13r31
    • May be localized or generalized
    • May be unilateral or bilateral
    • Submandibular, cervical, axillary, and inguinal lymph nodes may be involved
    • Enlarged lymph nodes are firm and tender, and they may be painful r35
  • Rash r12
    • Invariably present; absence of rash within 5 days of illness onset effectively rules out mpox infection r11
    • Although rash typically follows fever and other prodromal symptoms in classic endemic mpox, rash may be the first or only symptom in 2022-2023 outbreak–related cases r12r13r14r15
    • Initial rash on face is frequently described in endemic mpox cases; initial lesions in mucosal regions (oral, genital, perianal) have been more common in 2022-2023 outbreak–related cases, and proctitis is possible as well r15r16r33
    • CDC has urged vigilance for rash that may be consistent with mpox, especially in patients with epidemiologic risk factors; lesions can be confused with sexually transmitted infections, and therefore patients may present initially to outpatient settings such as sexual health clinics r16
    • Clinicians should undertake a thorough skin and mucosal (oral, genital, perianal) examination for characteristic lesions in patients presenting with potential mpox; this examination allows detection of lesions that the patient may not have been aware of r33
    • WHO has published an atlas of mpox lesions to aid in clinical recognition of mpox-associated skin findings r36
    • May be macular, papular, vesicular, or pustular; lesions evolve through this sequence before scabbing over and falling off
    • Overall duration of lesions, from initial appearance through to scabbing over and falling off, may range from 2 to 4 weeks r12
    • May be generalized or localized
    • May be discrete or confluent
    • Lesions are typically deep, firm, and well-demarcated; umbilication is often present
    • Lesions are typically around the same size, and with same morphology, on any part of body
    • Rash with nonclassic traits—few small lesions, more limited distribution, and asynchronous evolution on a given part of body—has been noted in 2022-2023 outbreak–related cases r32r34
      • A large international case series for the 2022-2023 outbreak found that most cases had 10 or fewer lesions, and more than 10% of cases presented with only a single genital ulcer r37
      • Anogenital lesions are especially common in 2022-2023 outbreak–related cases and have been reported in more than 70% of cases in several recent large case series and meta-analyses r37r38r39
    • If disseminated, rash has centrifugal distribution (concentrated on face and extremities)
    • Lesions may be present on palms and soles
    • Scarring and discoloration may remain after scabs have fallen off and healed

Causes and Risk Factors

Causes

  • Mpox virus r2r3r4
    • Member of the Orthopoxvirus genus in the Poxviridae family
    • Other members of the Orthopoxvirus genus that can cause diseases in humans include variola virus (smallpox virus), vaccinia virus, and cowpox virus; various other poxviruses cause diseases in animals
    • Mpox virus is the foremost orthopoxvirus affecting humans since the global eradication of smallpox r35r40
    • Natural reservoir of mpox virus is unknown; despite the disease's original name, rodents and other small mammals are implicated much more frequently than monkeys or other primates
    • 2 distinct mpox virus genetic groups (clades) have been characterized: clade I (formerly known as Central African or Congo Basin clade) associated with endemic outbreaks, and clade II (formerly known as West African clade), from which the 2022-2023 outbreak appears to have originated r1r8r12r41
    • International Committee on the Taxonomy of Viruses is considering renaming all of the orthopoxvirus species, including mpox virus; though the new WHO name "mpox" technically refers to the disease caused by mpox virus, many have started using "mpox" in reference to the virus as well r7
  • Transmission is via contact with an infected person or animal, or other materials contaminated with the virus r10r30
    • Virus is believed to enter body via broken skin, mucous membranes, or respiratory tract r1
    • Human to human transmission is primarily through direct contact with mpox lesions, lesion material, saliva, and respiratory secretions r1
      • Direct contact during intimate and sexual activity has been identified as the primary mode of exposure and transmission in 2022-2023 outbreak–related cases r10r30r37
      • Transmission to children is primarily through close nonsexual contact with caregivers and other household members r30r42
    • Human to human transmission risk via indirect contact (eg, shared clothing, bedding, towels, sex toys, other personal items) is considered relatively low r10
    • Vertical transmission from mother to child via the placenta or close contact during the intrapartum period is possible and has been noted in case reports r10r43r44
    • Rare cases of transmission via needlestick injury, piercing, and tattooing have been reported
    • Unknown at this time whether other bodily fluids and materials such as semen, vaginal fluids, urine, and feces can propagate infection, though mpox virus DNA may be detectable r10
    • Can also be transmitted from animals via bites or scratches, meat preparation, direct contact with infected animal matter, and indirect contact (eg, bedding)

Risk factors and/or associations

Age
  • 2022-2023 outbreak–related cases tend to occur at younger ages
    • Median patient age in the United States is 34 years r45
    • Median patient age worldwide is also 34 years; male patients aged 18 to 44 years account for nearly 80% of cases r8
Sex
  • For 2022-2023 outbreak–related cases with available sex data, over 95% of cases in the United States, as well as worldwide, have been in males r25r32
Ethnicity/race
  • For 2022-2023 outbreak–related cases in the United States with ethnicity and/or race data reported to CDC, approximately 32.0% of patients are Black, 31.1% are Hispanic, 29.9% are White, 3.0% are Asian American, and less than 3% are reported as other ethnicity or race; data are missing for many cases r45
Other risk factors/associations
  • Sexual activity, especially male to male sexual contact r15r16r46r47
    • Most 2022-2023 outbreak–related cases worldwide, including those in the United States, have been in men who identify as gay or bisexual or in other men who have sex with men
      • A large international case series published in 2022, reporting on 528 cases in 16 countries, found that 98% of cases were in gay or bisexual men, with sexual activity implicated in transmission in 95% of persons with infection r37
      • Early in the course of the US outbreak, per CDC data, a history of recent male to male sexual contact was self-reported in over 98% of male patients for whom such data was available; more recently, this proportion has declined to approximately 70%, with data missing for many cases r13r45
      • Per recent WHO data, among cases worldwide with reported sexual orientation, 84.1% of patients identified as gay or bisexual or other men who have sex with men r48
    • Mpox is not considered a sexually transmitted infection in the traditional sense, but it can be spread via close skin to skin contact during sexual activity, including kissing, touching, oral sex, and penetrative sex, and by shared bedding, linens, and clothing r49
    • History of multiple casual sexual encounters or multiple sexual partners further increases risk of exposure and infection r34
  • Sexually transmitted infections
    • Concomitant sexually transmitted infections were reported in 29% of patients diagnosed with mpox in a recent large, international case series r37
    • A large case series reporting on 1969 patients with mpox in the United States found that 41% had been diagnosed with one or more reportable sexually transmitted infections in the preceding year r50
  • HIV
    • Among 2022-2023 outbreak–related cases with known HIV status, 52% of cases worldwide have been positive for HIV; rates reported in European countries have ranged from 28% to 51% r8r51
    • A large case series reporting on 1969 patients with mpox in the United States found that HIV prevalence was 38% in this population r50
    • Unknown at this time whether HIV per se increases risk of mpox infection r51
  • Health care personnel r20
    • Health care personnel are at theoretical risk of mpox virus entry via their own unprotected skin or mucous membranes, through actions such as:
      • Touching a patient's skin, skin lesions, or bodily fluids
      • Touching contaminated materials such as linens or clothing
      • Allowing their own unprotected clothing to touch patient skin, skin lesions, bodily fluids, or contaminated materials such as linens or clothing
      • Being inside a patient's room or near a patient during aerosol-generating procedures
      • Close, prolonged presence near a patient
      • Accidental sharps injury with contaminated instruments r52
    • Degree of real-world risk to health care personnel of acquiring mpox after patient exposure appears to be very low; a recent report on 313 US health care personnel exposed to patients with mpox during the 2022-2023 outbreak found that despite low adherence to recommended use of personal protective equipment and postexposure prophylaxis vaccination, none of the monitored health care personnel acquired mpox r53
  • General public r21
    • Personal and household contacts are also at risk of mpox infection via direct and indirect contact with mpox lesions, lesion material, respiratory secretions, other bodily fluids, and contaminated surfaces or materials (eg, dishes, utensils, clothing, bedding, linens)

Diagnostic Procedures

Primary diagnostic tools

  • Mpox is diagnosed via laboratory detection of mpox virus in the setting of appropriate epidemiologic risk factors and clinical findings
  • CDC has defined a confirmed mpox case as: r11
    • 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 gene sequencing or
      • Isolation of mpox virus in culture from a clinical specimen
    • Suspect case
      • New rash characteristic of mpox or
      • Meets 1 epidemiologic criterion within 21 days of symptom onset and high clinical suspicion for mpox exists
    • 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 illness or
      • A rash does not develop within 5 days of illness onset or
      • High-quality clinical specimens fail to demonstrate presence of orthopoxvirus or mpox virus or antibodies
  • For 2022-2023 mpox outbreak–related cases, CDC states that all confirmed orthopox cases (ie, a suspect case with orthopoxvirus infection confirmed by a state or authorized commercial laboratory) are presumed to be mpox unless proven otherwise r15
  • WHO has also published interim guidance for mpox surveillance, reporting, case investigation, and contact tracing, for international application r28

Laboratory

  • Specific diagnostic tests
    • Possible cases of mpox should be reported to applicable local and state public health authorities to help guide diagnosis; CDC is also available for consultation through the Emergency Operations Center (telephone, 1-770-488-7100) r15r54
    • 2 tests are currently in use to establish presence of mpox infection; either or both may be used: r13r55
      • State laboratories that are part of the Laboratory Response Network and certain authorized commercial laboratories can perform generic orthopox real-time polymerase chain reaction testing on lesion material; testing detects the presence of undifferentiated orthopoxvirus DNA, and a positive result establishes a confirmed orthopox case
        • All confirmed orthopox cases in the United States are presumed to be mpox unless proven otherwise, as there are no other clinically significant orthopoxviruses in circulation r13
        • Once an orthopox case is confirmed, laboratories may forward specimens to CDC for further mpox-specific viral characterization and sequencing
      • Certain authorized commercial laboratories and CDC can perform mpox-specific real-time polymerase chain reaction testing on lesion material; this testing detects the presence of mpox DNA, and a positive result establishes a confirmed mpox case
        • Authorized commercial laboratories can perform this as initial testing, whereas CDC performs it as confirmatory testing on samples from established orthopox cases; commercial laboratories may forward specimens to CDC for further viral characterization and sequencing
    • Previously, other diagnostic tests for mpox and orthopox included viral culture and isolation, electron microscopy, immunohistochemistry, and testing for orthopox antibodies or antigens; although CDC case definitions still include these results, these modalities are no longer recommended in current practice r11r15r35
    • CDC recommends that swabs be collected for testing if: r32
      • Classic mpox rash is present or
      • Potential mpox rash is present and patient has epidemiologic risk factors as defined in CDC case definition (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)
    • Specimens should be collected with use of appropriate personal protective equipment, including gown, gloves, eye protection, and N95-comparable or higher-level respirator r17
    • Specimen type r13r17
      • Initial testing performed at Laboratory Response Network laboratories and authorized commercial laboratories is performed on lesion material; viral characterization at CDC can be performed on dry swabs of lesion material, swabs of lesion material in viral transport medium, or crusts r13r17
      • 2 to 3 lesion specimens per patient are suggested
      • Swab of lesion from any part of body is acceptable
      • CDC is evaluating feasibility of testing on other specimen types, such as blood or saliva
    • Consultation with CDC is required before submission of specimens to CDC; state and commercial laboratories may already have established processes in place to forward positive specimens to CDC r17r56
    • Complete information for specimen submission to CDC is available on the CDC website; highlights are as follows: r17r56
      • Dry swabs of lesion material, swabs of lesion material in viral transport medium, or viral crusts are acceptable
      • Synthetic swabs (eg, nylon, polyethylene terephthalate [eg, Dacron], other polyester) with plastic, wood, or thin aluminum shafts should be used; cotton swabs may interfere with polymerase chain reaction testing and should not be used
      • Specimens should be refrigerated (2 to 8 °C) or frozen (−20 °C or lower) promptly after collection; frozen samples can be stored for up to 60 days, depending on the specimen type
      • If transport media is used, only viral transport medium is accepted at this time
      • Turnaround time for CDC testing is 10 days
    • WHO has also published interim guidance for laboratory testing for mpox virus, for international application r57
  • Additional laboratory testing
    • HIV status of all sexually active adults and adolescents with suspected or confirmed mpox should be ascertained r58
    • Specific testing for sexually transmitted infections is warranted for patients presenting with genital or perianal ulcers, in order to narrow differential diagnosis and assess for concurrent infections. This may include: r24r29
      • Syphilis serologic tests
      • Nucleic acid amplification tests for gonorrhea and chlamydia
      • Nucleic acid amplification test or culture for herpes simplex virus (HSV-1 and HSV-2)
    • Additional routine laboratory testing may be warranted to assess clinical status and determine eligibility for specific therapies; some systemic antiviral treatments, such as tecovirimat and cidofovir, are contraindicated in severe renal impairment
    • For severe infections in patients with established mpox diagnoses in whom it is unclear whether disease manifestations are due to mpox or other infections, biopsy specimen of affected tissue can be submitted, after preapproval, to CDC's Infectious Diseases Pathology Branch for additional testing; instructions for specimen submission are available on the CDC website r59

Differential Diagnosis

Most common

  • Genital and perianal lesions
    • Genital herpes d1
      • Caused by HSV (herpes simplex virus), mostly HSV-2
      • Painful thin-walled vesicular lesions on erythematous base; often bilateral on labia, vulva, perineum, perianal areas, or shaft or glans of penis
      • Vesicles rupture to form small painful ulcers
      • Diagnosis confirmed by polymerase chain reaction, antigen assays, and microscopic examination
    • Syphilis d2
      • Caused by Treponema pallidum pallidum spirochete
      • Firm, generally single, painless genital lesion with clean base, indurated border, and associated regional painless adenopathy; frequently found in perineum, cervix, anogenital area, lips, oropharynx, and hands
      • Diagnosis confirmed with VDRL testing (Venereal Disease Research Laboratory) or RPR testing (rapid plasma reagin) followed by confirmatory treponemal antigen testing, demonstration of Treponema pallidum on darkfield microscopy, or detection with polymerase chain reaction
    • Chancroid d3
      • Caused by Haemophilus ducreyi
      • Nonindurated, painful, exudative genital ulcer with necrotic base that bleeds when scraped
      • Tender and suppurative inguinal adenopathy
      • Definitive diagnosis is determined by culture of exudate from lesion and exclusion of genital herpes and syphilis
    • Lymphogranuloma venereum d4
      • Caused by Chlamydia trachomatis
      • Unilateral small papules or pustules that are painless and may erode, resulting in formation of small ulcers
      • Tender inguinal lymphadenopathy, usually unilateral, is common
      • Diagnosis confirmed via culture or nucleic acid amplification testing, performed on swab of skin lesion or lymph node aspirate
    • Genital warts d5
      • Caused by HPV (human papillomavirus)
      • Flat, papular, or pedunculated growths in or around the anogenital area; warts are highly variable in size and appearance
      • Diagnosis is made by visual inspection of external genital lesions with ascertainment of typical genital wart morphology; biopsy can be diagnostic if lesions are atypical
    • Granuloma inguinale
      • Caused by Klebsiella granulomatis
      • Painless, beefy red, foul-smelling ulcer and absence of regional lymphadenopathy, although pseudobuboes may form
      • Diagnosis is usually clinical, but Giemsa- or Wright-stained smears may be confirmatory
  • Diffuse rash
    • Syphilis d2
      • Secondary syphilis can result in a maculopapular erythematous rash that involves the trunk and extremities, including palms and soles
      • Diagnosis confirmed with VDRL testing (Venereal Disease Research Laboratory) or RPR testing (rapid plasma reagin) followed by confirmatory treponemal antigen testing, demonstration of Treponema pallidum on darkfield microscopy, or detection with polymerase chain reaction
    • Varicella (chickenpox) d6
      • Caused by varicella-zoster virus
      • Lesions evolve from macules to papules to thin-walled vesicles, which become cloudy or pustular in appearance and may umbilicate before crusting; presence of lesions in various stages of healing is characteristic
      • Lesions are superficial and typically denser on trunk than on face and extremities r1
      • Diagnosis is usually clinical, but it may be confirmed by polymerase chain reaction assay, culture, direct antigen testing, or serology
    • Disseminated herpes zoster (shingles) infection d7
      • Caused by reactivation of varicella-zoster virus acquired from previous varicella infection or vaccination
      • Usually has limited dermatomal distribution, but disseminated disease may occur, especially in immunocompromised patients
      • Erythematous maculopapular lesions evolve over several days into clusters of vesicles, which may coalesce to form bullae
      • Diagnosis is usually clinical, but it may be confirmed by viral culture, polymerase chain reaction, Tzanck test, or direct fluorescent antibody test
    • Disseminated herpes simplex infection d1
      • Immunocompromised patients may develop severe disseminated infection
      • Superficial painful vesicles that can rupture to form small ulcers
      • Diagnosis is confirmed by polymerase chain reaction, antigen assays, and microscopic examination
    • Molluscum contagiosum d8
      • Caused by molluscum contagiosum virus
      • In children, trunk and proximal extremities are commonly affected, although lesions can occur on any part of body, including face and genitals, via autoinoculation. Sexually transmitted infection in adults primarily affects the perineum and thighs
      • Skin-colored, dome-shaped, smooth, pearly papules with central umbilication
      • Diagnosis is usually clinical, but histopathology can be diagnostic
    • Other poxvirus infections r4
      • Other orthopoxviruses that can cause disease in humans include the causative agents of smallpox, vaccinia, and cowpox
      • Overall clinical course and features of mpox are quite similar to those of smallpox, which has been eradicated globally and is no longer seen r12r35
      • Lymphadenopathy is frequently present in mpox but absent in smallpox r12r14
      • Vaccinia occurs in the context of smallpox vaccination or direct contact with the unhealed inoculation site of a person who has recently been vaccinated
      • Cowpox occurs after exposure to infected animals (cows and others)
      • CDC and certain authorized commercial laboratories can perform mpox-specific polymerase chain reaction testing to differentiate mpox from other orthopoxviruses; however, CDC states that there are no other clinically significant orthopoxviruses in circulation in the United States at this time r13

Treatment

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

Admission criteria

  • Patients with mild disease can be managed at home, with appropriate isolation and infection control precautions in place
  • Admission may be appropriate for the same patient groups who may be considered for antiviral therapy:
    • 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
  • Hospitalization rates around 10% have been reported internationally for 2022-2023 outbreak–related cases, with pain management and treatment of secondary bacterial infections the most commonly reported reasons r37r60

Recommendations for specialist referral

  • Mpox is a reportable disease; suspected cases should be reported to relevant hospital officials (for inpatients) and to local and state public health authorities (for all patients), to facilitate necessary reporting and further diagnostic and management steps

Treatment Options

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

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): r18

  • 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 r29

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 r18

  • Tecovirimat r19r61
    • 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 r62
    • 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, and tecovirimat resistance or intolerance r18
    • 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 r18r63
    • 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 r64
    • 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 r19r63
      • 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 r63
        • 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 r65
    • 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 r64
    • A recent 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 r66
  • Cidofovir r67
    • 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
    • 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) r68
    • 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
    • Can be considered for prophylactic use after mpox exposure if smallpox or mpox vaccination is contraindicated
    • 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 r69
    • 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
    • BLACK BOX WARNING for increased mortality risk when used for prolonged durations
    • No contraindications noted in prescribing information
  • Trifluridine r70
    • 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; prophylactic use can be considered for patients with eye-adjacent lesions r71
    • 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 mpox disease manifestations or disease-related complications, and may include the following: r72r73

  • Fever
    • Antipyretic medications and external cooling measures
  • Pain r72
    • 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, petroleum jelly, or colloidal oatmeal
  • 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

Additional guidance has been developed for the following specific clinical manifestations of mpox:

  • Ocular involvement r71r74r75r76
    • Ocular involvement is an uncommon but potentially serious manifestation of mpox infection
    • Though high rates (up to 27% prevalence) of ocular involvement have been reported with endemic mpox disease, less than 1% of 2022-2023 outbreak–related cases have had eye involvement r77
    • 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 mpox 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 mpox 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
    • Hand hygiene and avoidance of eye rubbing should be discussed with patients who have mpox, to minimize risk of eye involvement
  • Skin lesions
    • General measures r78
      • Wash skin with mild soap and water
      • Adhere to recommended isolation and infection control measures
      • Antimicrobial agents are required only if concern for bacterial infection exists
      • Silicone-based gels or sheeting may be used after lesions have healed, if there are scarring concerns
      • Sun protection should be emphasized during and after lesion resolution to minimize pigmentation and scarring issues
      • Lesions and scabs should not be scratched or unroofed
      • Baths, sitz baths, and warm or cool compresses may help to sooth irritated skin
    • Severe lesions r79
      • Wounds should be cleansed with mild soap and water
      • Antimicrobial soaks as part of wound cleaning may help remove biofilms and colonizing organisms
      • Topical plain white petrolatum and occlusive nonstick dressings should be used to promote healing
      • Protective coatings such as white petrolatum, zinc oxide paste, or silicone film should be used to protect large or highly exudative wounds
      • Adult incontinence pads may help with management of perianal discharge or exudate
      • Routine use of topical antimicrobial agents is not indicated and may be harmful
      • Specialist consultation should be sought for severe wounds with significant involvement of high-risk anatomical sites, such as the eyelids, perioral area, ears, genitals, and perianal region
      • Significant pitting or scarring may occur as lesions heal
      • There should be low threshold to test for and treat potential coinfections

Drug therapy

  • There are no treatments approved specifically for mpox; dosing recommendations are based on approved uses in smallpox or other viral infections
  • Antivirals
    • Tecovirimat r19r61
      • Oral
        • Administer within 30 minutes after a full meal containing moderate or high fat (approximately 600 calories and 25 grams of fat), or after a feeding for nursing or bottle-fed infants or children r63
        • Capsules may be opened and mixed with water or food for those who cannot swallow capsules, especially infants and children r63
        • Tecovirimat Oral capsule; Neonates weighing less than 3 kg: 33.3 mg PO every 12 hours. Standard duration is 14 days, but may be longer or shorter.
        • Tecovirimat Oral capsule; Neonates weighing 3 to 5 kg: 50 mg PO every 12 hours. Standard duration is 14 days, but may be longer or shorter.
        • Tecovirimat Oral capsule; Infants weighing less than 3 kg: 33.3 mg PO every 12 hours. Standard duration is 14 days, but may be longer or shorter.
        • Tecovirimat Oral capsule; Infants and Children weighing 3 to 5 kg: 50 mg PO every 12 hours. Standard duration is 14 days, but may be longer or shorter.
        • Tecovirimat Oral capsule; Infants and Children weighing 6 to 12 kg: 100 mg PO every 12 hours. Standard duration is 14 days, but may be longer or shorter.
        • Tecovirimat Oral capsule; Children weighing 13 to 24 kg: 200 mg PO every 12 hours. Standard duration is 14 days, but may be longer or shorter.
        • Tecovirimat Oral capsule; Children and Adolescents weighing 25 to 39 kg: 400 mg PO every 12 hours. Standard duration is 14 days, but may be longer or shorter.
        • Tecovirimat Oral capsule; Children and Adolescents weighing 40 to 119 kg: 600 mg PO every 12 hours. Standard duration is 14 days, but may be longer or shorter. With the CDC or a mpox treatment expert, consider early use of combination therapy (i.e., tecovirimat plus VIGIV, brincidofovir, or cidofovir) in people with HIV and severe disease.
        • Tecovirimat Oral capsule; Adolescents weighing 120 kg or more: 600 mg PO every 8 hours. Standard duration is 14 days, but may be longer or shorter. With the CDC or a mpox treatment expert, consider early use of combination therapy (i.e., tecovirimat plus VIGIV, brincidofovir, or cidofovir) in people with HIV and severe disease.
        • Tecovirimat Oral capsule; Adults weighing 40 to 119 kg: 600 mg PO every 12 hours. Standard duration is 14 days, but may be longer or shorter. With the CDC or a mpox treatment expert, consider early use of combination therapy (i.e., tecovirimat plus VIGIV, brincidofovir, or cidofovir) in people with HIV and severe disease.
        • Tecovirimat Oral capsule; Adults weighing 120 kg or more: 600 mg PO every 8 hours. Standard duration is 14 days, but may be longer or shorter. With the CDC or a mpox treatment expert, consider early use of combination therapy (i.e., tecovirimat plus VIGIV, brincidofovir, or cidofovir) in people with HIV and severe disease.
      • Intravenous
        • Transition patients to oral therapy to complete the treatment course as soon as oral therapy is tolerated; the duration of IV tecovirimat is 14 days if the patient's condition necessitates IV administration r63
        • Tecovirimat Solution for injection; Neonates weighing less than 6 kg: 6 mg/kg/dose IV every 12 hours for 14 days.
        • Tecovirimat Solution for injection; Infants and Children weighing less than 12 kg: 6 mg/kg/dose IV every 12 hours for 14 days.
        • Tecovirimat Solution for injection; Children and Adolescents weighing 13 to 34 kg: 6 mg/kg/dose IV every 12 hours for 14 days.
        • Tecovirimat Solution for injection; Children and Adolescents weighing 35 to 119 kg: 200 mg IV every 12 hours for 14 days. With the CDC or a mpox treatment expert, consider early use of combination therapy (i.e., tecovirimat plus VIGIV, brincidofovir, or cidofovir) in people with HIV and severe disease.
        • Tecovirimat Solution for injection; Adolescents weighing 120 kg or more: 300 mg IV every 12 hours for 14 days. With the CDC or a mpox treatment expert, consider early use of combination therapy (i.e., tecovirimat plus VIGIV, brincidofovir, or cidofovir) in people with HIV and severe disease.
        • Tecovirimat Solution for injection; Adults weighing 35 to 119 kg: 200 mg IV every 12 hours for 14 days. With the CDC or a mpox treatment expert, consider early use of combination therapy (i.e., tecovirimat plus VIGIV, brincidofovir, or cidofovir) in people with HIV and severe disease.
        • Tecovirimat Solution for injection; Adults weighing 120 kg or more: 300 mg IV every 12 hours 14 days. With the CDC or a mpox treatment expert, consider early use of combination therapy (i.e., tecovirimat plus VIGIV, brincidofovir, or cidofovir) in people with HIV and severe disease.
    • Cidofovir r80
      • Administer oral probenecid with each cidofovir dose to minimize nephrotoxicity potential
      • Cidofovir Solution for injection; Adults: 5 mg/kg/dose IV once weekly for 2 weeks, then 5 mg/kg/dose IV every 2 weeks. For people with HIV and severe disease, guidelines recommend considering 5 mg/kg/dose IV once weekly for 2 doses as an adjunct to tecovirimat.
    • Brincidofovir r81
      • Administer on an empty stomach
      • Brincidofovir Oral suspension; Neonates: 6 mg/kg/dose PO once weekly for 2 doses (on days 1 and 8).
      • Brincidofovir Oral suspension; Infants and Children weighing less than 10 kg: 6 mg/kg/dose PO once weekly for 2 doses (on days 1 and 8).
      • Brincidofovir Oral suspension; Children and Adolescents weighing 10 to 47 kg: 4 mg/kg/dose PO once weekly for 2 doses (on days 1 and 8).
      • Brincidofovir Oral suspension; Children and Adolescents weighing 48 kg or more: 200 mg PO once weekly for 2 doses (on days 1 and 8).
      • Brincidofovir Oral suspension; Adults weighing less than 48 kg: 4 mg/kg/dose PO once weekly for 2 doses (on days 1 and 8).
      • Brincidofovir Oral tablet; Adults weighing 48 kg or more: 200 mg PO once weekly for 2 doses (on days 1 and 8). For people with HIV and severe disease, guidelines recommend considering brincidofovir as an adjunct to tecovirimat.
    • Trifluridine
      • Trifluridine Ophthalmic drops, solution; Children and Adolescents: 1 drop in the affected eye(s) every 2 hours (Max: 9 drops/day) until reepithelialization, then 1 drop in the affected eye(s) every 4 hours (Min: 5 drops/day) for 7 days. Continue treatment until all periocular lesions have healed. Max duration: 21 days.
      • Trifluridine Ophthalmic drops, solution; Adults: 1 drop in the affected eye(s) every 2 hours (Max: 9 drops/day) until reepithelialization, then 1 drop in the affected eye(s) every 4 hours (Min: 5 drops/day) for 7 days. Continue treatment until all periocular lesions have healed. Max duration: 21 days.
  • Probenecid r80
    • Administer oral probenecid with each cidofovir dose to minimize nephrotoxicity potential
    • Probenecid Oral tablet; Adults: 2 g PO given 3 hours prior to each cidofovir infusion, followed by 1 g PO at 2 and 8 hours following completion of the infusion.
  • Vaccinia immune globulin r82
    • Human Vaccinia Virus Immune Globulin Solution for injection; Neonates: 6,000 units/kg/dose IV as soon as symptoms appear; may consider a higher initial dose of 9,000 units/kg/dose IV for severe disease. Higher doses (e.g., 9,000 units/kg/dose, 24,000 units/kg/dose) may be considered if there is no response to the initial dose. Repeat dosing may be considered depending on the severity of symptoms and response to treatment. Base dose on actual body weight.
    • Human Vaccinia Virus Immune Globulin Solution for injection; Infants, Children, and Adolescents: 6,000 units/kg/dose IV as soon as symptoms appear; may consider a higher initial dose of 9,000 units/kg/dose IV for severe disease. Higher doses (e.g., 9,000 units/kg/dose, 24,000 units/kg/dose) may be considered if there is no response to the initial dose. Repeat dosing may be considered depending on the severity of symptoms and response to treatment. Base dose on actual body weight.
    • Human Vaccinia Virus Immune Globulin Solution for injection; Adults: 6,000 units/kg/dose IV as soon as symptoms appear; may consider a higher initial dose of 9,000 units/kg/dose IV for severe disease. Higher doses (e.g., 9,000 units/kg/dose, 24,000 units/kg/dose) may be considered if there is no response to the initial dose. Repeat dosing may be considered depending on the severity of symptoms and response to treatment. Base dose on actual body weight. For people with HIV and severe disease, guidelines recommend considering 6,000 to 9,000 Units/kg IV as an adjunct to tecovirimat.
  • Vaccines

Comorbidities

  • HIV r51r83r84
    • Patients with advanced or uncontrolled HIV are at higher risk of severe or complicated mpox infection and prolonged mpox symptoms; effective antiretroviral therapy appears to attenuate risk r85
    • In a recent report describing 57 adults hospitalized with severe manifestations of mpox for which CDC provided clinical consultation, 82% had HIV infection and 72% had known CD4 count less than 50 cells/mm³ r86
    • Signs and symptoms of mpox are generally similar in patients with and without HIV; significant immunocompromise such as in advanced or uncontrolled HIV may predispose to disseminated or atypical rash (ie, genital lesions or confluent rash)
    • Antiretroviral therapy and prophylaxis for opportunistic infections should be continued in all patients with HIV who develop mpox
    • Mpox vaccination, antiviral treatments, and close monitoring are priorities for this population and should account for viral suppression and CD4 count in weighing risk of severe outcomes from mpox
    • Assessment for drug interactions between available antiviral treatments for mpox and antiretroviral therapy for HIV is advised
    • Tecovirimat should especially be considered for patients with mpox who have advanced or uncontrolled HIV disease, owing to risk of severe mpox disease; treatment should be initiated as early as possible in these patients
    • Other antiviral therapies (ie, cidofovir, brincidofovir, VIGIV) can be considered in severe cases with disease progression or lack of improvement despite tecovirimat
    • Vaccination with Jynneos vaccine is considered safe in patients with HIV; ACAM2000 vaccine should not be used in this population, regardless of immune status, owing to risk of progressive vaccinia and other severe adverse effects
  • Other immunocompromise r51
    • Significant immunocompromise is considered to include the following:
      • Moderate or severe primary immunodeficiency
      • Active treatment for a solid tumor or hematologic malignancy
      • Transplant-associated immunosuppression
      • Active treatment with high-dose corticosteroids, alkylating agents, antimetabolites, other transplant-related immunosuppressive drugs, severely immunosuppressive chemotherapy agents, tumor necrosis factor blockers, or other immunosuppressive or immunomodulatory agents
      • History of CAR T-cell therapy (using chimeric antigen receptors) or hematopoietic cell transplant
    • Patients with significant immunocompromise are at increased risk of severe mpox
    • Significant immunocompromise may predispose to disseminated or atypical mpox lesions
    • Assessment for drug interactions between available antiviral treatments for mpox and immunosuppressive therapies is advised
    • Tecovirimat is the antiviral therapy of choice in patients with mpox who have significant immunocompromise
    • Other antiviral therapies can be considered based on individual clinical circumstances
    • Vaccination with Jynneos vaccine is considered safe in patients who are immunocompromised, including those with primary immunodeficiency or from immunosuppressive therapies; ACAM2000 vaccine should not be used, due to risk of progressive vaccinia and other severe adverse effects

Special populations

  • Pregnant or breastfeeding patients r44r87
    • Very limited data exist regarding mpox in pregnancy; it is unclear whether pregnancy increases risk of infection or more severe outcomes, although pregnant and breastfeeding patients are still considered a priority group for antiviral treatment
    • Adverse pregnancy outcomes, including vertical transmission and fetal loss, have been reported in patients with mpox infection during pregnancy r43
    • Signs and symptoms of mpox are similar in pregnant and nonpregnant patients
    • If antiviral treatment is deemed to be indicated, after consultation with CDC, then tecovirimat should be first line therapy for patients who are pregnant, recently pregnant, or breastfeeding
      • In animal studies, tecovirimat did not demonstrate any specific fetal effects, whereas cidofovir and brincidofovir showed evidence of teratogenicity
      • There is no human data on tecovirimat in breastfeeding; it is unknown whether levels of tecovirimat expressed in breastmilk are sufficient for treatment of a breastfeeding child with mpox
    • Jynneos vaccine data in humans are insufficient to assess vaccine-associated risks in pregnancy and breastfeeding, but Jynneos vaccination can be considered in patients who are otherwise eligible; ACAM2000 vaccine is contraindicated in pregnancy and breastfeeding, owing to risk of vaccinia virus infection and other severe adverse effects
    • Patients in isolation for mpox should not breastfeed and should not have direct skin to skin contact with infants until criteria for discontinuation of isolation for mpox have been met
  • Children and adolescents r42r88
    • Reported pediatric cases in the current outbreak have been infrequent and generally mild; current evidence suggests that cases in children are generally not more severe than those in adults
    • Household exposures are the main route of transmission for children; male to male sexual contact is the predominant route for adolescents, as for adults
    • Adolescents present similarly to adults, but rash distribution differs in younger children; in a recent report on pediatric patients with mpox in the United States, rash distribution in children was mainly on the trunk and face, and no children younger than 12 years had anogenital lesions r88
    • Diagnostic testing recommendations are similar for children and adults
    • Management considerations are similar for children and adults
    • Antiviral treatment should be considered for children and adolescents with: r42
      • Severe disease or severe disease-related complications (eg, hemorrhagic disease, confluent lesions, sepsis, encephalitis, ocular disease, bronchopneumonia, or other conditions requiring hospitalization)
      • Severe immunocompromise or conditions affecting skin integrity
      • Infection involving high-risk anatomical areas (eg, eyes, face, genitals, anus) with potential for serious adverse outcomes
      • Age younger than 1 year
    • Tecovirimat is first line antiviral treatment for children and adolescents; other treatments, including cidofovir, brincidofovir, and VIGIV, can be considered, but they should be used with caution (owing to potential toxicity) r42
    • No vaccines are currently licensed specifically for mpox prevention in children or adolescents; Jynneos vaccine can be offered for pediatric cases under an FDA emergency use authorization, after consultation with jurisdictional health authorities and CDC r42r89
      • No significant adverse events have been reported to date in infants and children who have received Jynneos vaccine
      • Pediatric data are lacking for ACAM2000 vaccine; many serious adverse effects, including progressive vaccinia and encephalitis, were reported in young children when the vaccine precursor to ACAM2000, which also contained replication-competent vaccinia virus, was used for smallpox prevention up through the early 1970s
    • VIGIV and tecovirimat can also be considered for use as mpox postexposure prophylaxis through EA-IND authorization if vaccines are otherwise contraindicated; effectiveness of these medications as postexposure prophylaxis is unknown r42

Complications and Prognosis

Complications

  • Pitted scarring (pockmarks) is the most common long-term sequela for survivors r35
  • Ocular infections can result in corneal scarring and permanent vision loss r35
  • Oral lesions and regional lymphadenopathy can lead to difficulties with swallowing and thus with eating and drinking r35
  • Vomiting and diarrhea can result in severe dehydration r35
  • Perianal lesions can lead to severe pain, tenesmus, and bleeding r32
  • Secondary bacterial infections of skin r35
  • Secondary infections of lungs can result in bronchopneumonia and respiratory distress, potentially requiring intubation r35
  • Neurologic complications include encephalitis and transverse myelitis r35r58
  • Cardiac complications include myocarditis and pericardial disease r58
  • Urologic complications include urethritis and penile necrosis r58
  • Rheumatologic complications include arthritis and synovitis r29
  • Obstructions (eg, in the lungs or gastrointestinal tract), can occur secondary to strictures, lymphadenopathy, and edema r29
  • Septicemia r35
  • Hemodynamic instability may require vasopressor support r58
  • Death

Prognosis

  • Mpox has a mild, self-limited course for most patients r5r6r32
  • 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 multi-country outbreak has been substantially lower, at less than 0.2% r5r6r8
  • Mortality is higher in children and young adults; disease is more severe in persons with immunocompromise, most notably HIV r1r58
    • 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) r85
  • 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%) r90
    • Of 24 persons with HIV for whom such data were available, all had advanced HIV, typically with CD4 count less than 50 cells/mm³

Screening and Prevention

Prevention

  • General infection control measures r91r92
    • Avoid close, skin to skin contact, including intimate or sexual contact, with anyone that has an mpox-like rash r46
    • 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 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 r93
      • 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 r93
    • 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
    • Isolating with animals in the home r21r94
      • 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 r49
  • Infection control in health care settings r20
    • Regarding prevention of mpox transmission in health care settings, CDC references 2007 guidelines for preventing transmission of infectious agents in these settings r95
    • 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 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 r96
    • 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 r49
  • Safer sex practices
    • Male to male intimate and sexual contact between gay, bisexual, and other men who have sex with men has been the primary mode of transmission in the 2022-2023 outbreak–related cases; various harm reduction efforts have focused on safer sex practices in these populations r8
    • CDC has issued recommendations for safer sexual practices to help reduce the risk of mpox exposure and transmission, including: r47
      • 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
    • 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 r47r97
  • 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 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 r20
      • 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 r20
      • 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 r20r23
      • 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 r22
    • CDC recommends that mpox vaccination be offered to: r22r98
      • Gay, bisexual, or other men who have sex with men, transgender, 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 front-line healthcare workers, or for the general public at large, is not recommended at this time r24
    • 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 mpox is conferred by previous smallpox vaccination; CDC recommends following the same vaccination schedules as for those not previously vaccinated r22
  • 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 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 r23
    • 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 r15
    • 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: r22
      • 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 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 r24
    • Other agents for postexposure prophylaxis r13r18r42
      • 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 r22r99r100
      • 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 r89
      • 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
        • 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 r99
        • 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 r99
      • 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 r22r89r101
        • 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 r102
      • CDC is collecting data on Jynneos vaccine efficacy in the setting of the 2022-2023 outbreak r22
        • 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 r42r51r87
        • Elicited higher peak neutralizing antibody titers against smallpox compared with ACAM2000 in clinical trials, with better safety profile r103
        • Less potential for adverse events compared with ACAM2000 vaccine r22
        • Can be used in certain immunocompromised patients in whom ACAM2000 vaccine is contraindicated r103
      • Generally well-tolerated, with few adverse reactions noted in clinical studies r104
      • 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 r100
        • 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 r22r100
        • 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 r105
      • 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
      • Current vaccination efforts as part of the outbreak response in the United States are primarily deploying Jynneos vaccine; any consideration of ACAM2000 should be made in consultation with CDC r22
      • 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: r22
        • 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
      • 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 r105
        • 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 r22r105
        • 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 interim guidance on vaccines and immunization for mpox, for international application; WHO and CDC recommendations are largely congruent r106
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