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Aug.16.2022

Monkeypox

Synopsis

Key Points

  • Monkeypox is a zoonotic viral disease spread via direct contact, respiratory secretions, and contaminated materials and surfaces r1r2r3r4
  • Monkeypox is caused by monkeypox virus, which belongs to the Orthopoxvirus genus of the Poxviridae family; other members of Orthopoxvirus include variola virus (which causes smallpox), vaccinia virus (used in smallpox vaccines), cowpox virus, and various other animal poxviruses r3
  • Monkeypox classically presents with rash, fever, lymphadenopathy, and a clinical course similar to that of smallpox but milder; case fatality rates of 3% to 6% have been reported in African countries where the disease is endemic, but cases detected in the United States have not resulted in any deaths to date r2r5r6
  • Monkeypox is endemic in several African countries, and until 2022, nearly all reported cases arose in Africa, with rare sporadic cases elsewhere; in 2022, a multi-country outbreak arose in nonendemic countries, including the United States, with atypical clinical presentations and most cases identified in men who have sex with men r7
    • US has declared the ongoing 2022 multi-country outbreak a public health emergency; CDC provides frequent updates online regarding the domestic outbreak situation r8
    • WHO has declared the 2022 multi-country outbreak a public health emergency of international concern, and provides frequent updates online regarding the international outbreak situation r9
  • Monkeypox should be considered in a patient with appropriate clinical features, especially rash, and potential exposure to monkeypox virus via contact with high-risk people, animals, or animal products, or travel to high-risk countries r10
  • Classically, there are prodromal symptoms of fever, chills, headache, myalgias, arthralgias, fatigue, and lymphadenopathy, with characteristic rash first appearing within several days of fever; in 2022 outbreak cases these symptoms may be very mild, be absent altogether, be concurrent with rash, or even develop after rash first appears r11r12r13r14
  • Rash is invariably present in monkeypox, with skin lesions that are typically deep-seated, well-demarcated, and umbilicated; initial lesions in mucosal regions (oral, genital, perianal) have been common in 2022 outbreak cases r14r15
  • Monkeypox is diagnosed via laboratory detection of monkeypox virus in the setting of appropriate epidemiologic risk factors and clinical findings
  • Diagnostic testing for monkeypox should be undertaken in consultation with public health authorities and may consist of either generic orthopox or monkeypox-specific real-time polymerase chain reaction testing of lesion material from swabs; laboratories may forward specimens from positive cases to CDC for further viral characterization and sequencing r11r16
  • Differential diagnosis for monkeypox includes other, more common causes of localized genital lesions and rash; the overall clinical features of monkeypox are similar to those of smallpox, which has been eradicated worldwide
  • Most patients with monkeypox have mild, self-limited disease that can be managed with supportive care; antiviral medications can be considered for patients with severe disease, high risk of severe disease, and infection involving high-risk anatomic areas r17
  • Currently there are no treatments approved specifically for monkeypox virus infection, but several antiviral agents originally developed for treatment of smallpox and other viral infections may be considered r18
  • Infection control measures, in both health care and home settings, are vital to minimize exposure and infection risk; they include appropriate isolation, hygiene measures, and use of personal protective equipment r19r20
  • Exposed persons should be monitored for symptoms and have an exposure risk assessment performed; postexposure prophylaxis with smallpox vaccination is recommended for high-risk exposures and can be considered for intermediate-risk exposures r21r22
  • One vaccine (Jynneos) is licensed in the United States for prevention of monkeypox and smallpox, and another (ACAM2000) is licensed for prevention of smallpox but considered effective for prevention of monkeypox as well; vaccination is recommended as preexposure prophylaxis for select laboratory and health care personnel at ongoing risk for occupational exposure and can be used as postexposure prophylaxis for persons who have had high-risk or intermediate-risk exposures r17r21r22
  • For the 2022 outbreak, some public health jurisdictions are employing an expanded approach to postexposure prophylaxis, offering vaccination to individuals at increased risk of recent monkeypox exposure, even without documented exposure to someone with confirmed monkeypox r23
  • CDC Emergency Operations Center (telephone, 1-770-488-7100) is available for consultation regarding appropriate utilization of medical countermeasures for monkeypox and can facilitate obtaining antiviral medications and vaccines from the National Strategic Stockpile

Urgent Action

  • Clinicians should be vigilant for rash that may be consistent with monkeypox, particularly in patients with established high-risk epidemiologic features (ie, contact with someone with similar rash or confirmed monkeypox diagnosis, close contact with people in a social network with monkeypox activity, history of recent international travel to country with confirmed cases) r10r15
  • Suspected monkeypox cases should be reported to relevant hospital and local and state public health authorities (to facilitate necessary reporting and further diagnostic and management steps)

Pitfalls

  • Monkeypox cases in the ongoing 2022 outbreak event have had atypical clinical features, including absence of classic prodromal symptoms (including fever and lymphadenopathy) and predilection for initial lesions to appear in the genital and perianal regions r14
  • Monkeypox lesions in the genital and perianal regions can be easily confused with sexually transmitted infections by patients and clinicians alike, and therefore patients may initially present to outpatient settings such as sexual health clinics for care; coinfections with monkeypox and sexually transmitted diseases have been reported, and presence of a sexually transmitted infection does not preclude monkeypox r14r24

Terminology

Clinical Clarification

  • Monkeypox is a zoonotic viral disease spread via direct contact, respiratory secretions, and contaminated materials and surfaces r1r2r3r4
  • Monkeypox is caused by monkeypox virus, which belongs to the Orthopoxvirus genus of the Poxviridae family; other members of Orthopoxvirus include variola virus (which causes smallpox), vaccinia virus (used in smallpox vaccines), cowpox virus, and various other animal poxviruses r1r3r4
  • Monkeypox is so named as it was first detected in monkeys; the natural host reservoir remains unknown, but rodents and other small mammals are most frequently implicated r1r3r4
  • Monkeypox classically presents with rash, fever, lymphadenopathy, and a clinical course similar to that of smallpox but milder; case fatality rates of 3% to 6% have been reported in African countries where the disease is endemic, but cases detected in the United States have not resulted in any deaths to date r2r5r6r7
  • Monkeypox is endemic in several African countries, and until 2022, nearly all reported cases arose in Africa, with rare sporadic cases elsewhere; in 2022, a multi-country outbreak arose in nonendemic countries, including the United States, with atypical clinical presentations and most cases identified in men who have sex with men r7r25
    • First known significant outbreak of human monkeypox in the United States was in 2003 and involved 47 confirmed and probable cases that were traced to infected pet prairie dogs; no more outbreaks occurred in the United States until the 2022 outbreak r5r6
    • US has declared the ongoing 2022 multi-country outbreak a public health emergency; CDC provides frequent updates online regarding the domestic outbreak situation r8
    • WHO has declared the 2022 multi-country outbreak a public health emergency of international concern, and provides frequent updates online regarding the international outbreak situation r9

Classification

  • CDC case definitions: r10
    • Suspect case
      • New rash characteristic of monkeypox or
      • Meets 1 epidemiologic criterion within 21 days of symptom onset and high clinical suspicion for monkeypox
    • Probable case
      • Criteria met for suspect case and
      • No other known recent orthopoxvirus exposure (eg, via smallpox vaccination) and
      • Orthopoxvirus infection confirmed by one of the following:
        • Detection of orthopoxvirus DNA by polymerase chain reaction testing of a clinical specimen or
        • Presence of orthopoxvirus demonstrated by immunohistochemistry or electron microscopy or
        • Detection of anti-orthopoxvirus IgM antibody between 4 and 56 days after rash onset
      • CDC has stated that for the ongoing 2022 outbreak, all confirmed orthopoxvirus infection cases in the United States are presumed to be monkeypox unless proven otherwise r14
    • Confirmed case
      • Criteria met for suspect case and
      • Monkeypox infection confirmed by one of the following:
        • Detection of monkeypox virus DNA by polymerase chain reaction testing or next-generation sequencing of a clinical specimen or
        • Isolation of monkeypox virus in culture from a clinical specimen
  • WHO case definitions for the ongoing 2022 multi-country outbreak event are slightly different: r26
    • Suspected case
      • Unexplained acute rash or skin lesions in a person of any age and
      • One or more of the following:
        • Headache
        • Acute onset of fever
        • Lymphadenopathy
        • Myalgia
        • Back pain
        • Profound weakness
      • And other common causes of acute rash deemed incompatible with the clinical presentation
    • Probable case
      • Criteria met for suspected case and
      • One or more of the following:
        • Confirmed epidemiologic connection to a probable or confirmed monkeypox case within 21 days of symptom onset, via face to face exposure, direct physical contact, or contact with contaminated materials
        • Multiple or anonymous sexual partners within 21 days of symptom onset
        • Detection of anti-orthopoxvirus IgM antibody between 4 and 56 days after rash onset, or a four-fold rise in IgG antibody titers based on acute (up to day 5-7) and convalescent (after day 21) samples, in the absence of other known orthopoxvirus exposure (eg, via smallpox vaccination)
        • Confirmed orthopoxvirus infection (eg, via PCR or sequencing)
    • Confirmed case
      • Criteria met for suspected or probable case and
      • Laboratory confirmation of monkeypox virus DNA via real-time polymerase chain reaction or sequencing

Diagnosis

Clinical Presentation

History

  • Monkeypox should be considered in a patient with appropriate clinical features, especially rash, and potential exposure to monkeypox virus via contact with high-risk people, animals, or animal products, or travel to high-risk countries r10
  • Epidemiologic history
    • 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 monkeypox per CDC case definitions: r10
      • Contact with another case or cases with a similar rash or diagnosis of confirmed or probable monkeypox or
      • Close or intimate in-person contact with persons in a social network experiencing monkeypox activity, such as men who have sex with men or
      • Travel outside the United States to a country with confirmed monkeypox or where monkeypox 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 r12r13
    • Incubation period ranges from 1 to 2 weeks; patients may be asymptomatic during this time
    • 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
    • Though prodromal symptoms preceding rash are typical of classic endemic monkeypox, atypical clinical presentations are common in 2022 outbreak cases; these symptoms may be very mild, be absent altogether, be concurrent with rash, or even develop after rash first appears r11r12r13r14
      • Of 2022 outbreak cases reported to CDC, aside from rash, the symptoms reported most frequently during the course of illness are malaise (70%), fever (64%), lymphadenopathy (63%), chills (61%), headache (57%), and myalgia (55%) r11
    • Rash is invariably present in monkeypox infection; absence of rash within 5 days of illness onset rules out monkeypox r10
      • 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 r12r13r14
      • Initial rash on face or in oral cavity is commonly described in classic endemic monkeypox; initial rash in mucosal regions (oral, genital, perianal) is much more common in 2022 outbreak cases r27r28
      • Classic endemic monkeypox 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 outbreak cases r25r27
      • Lesions evolve through macular, papular, vesicular, and pustular morphologies before scabbing over and resolving
      • Lesions can be extremely painful until they heal
      • Anorectal pain, tenesmus, and rectal bleeding can result from perianal lesions; these can be presenting complaints, particularly if lesions are not readily visible r27r28
      • Patients are contagious until all lesions have scabbed over and healed with a fresh layer of intact skin
    • 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

Physical examination

  • Fever
    • Temperature is often between 38.5 °C and 40.5 °C r29
    • Very common in classic endemic monkeypox; present in 64% of 2022 outbreak cases reported to CDC r11
  • Lymphadenopathy r13
    • Very common (90% of cases) in classic endemic monkeypox; present in 63% of 2022 outbreak cases reported to CDC r1r11
    • 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 r29
  • Rash r13
    • Invariably present; absence of rash within 5 days of illness onset effectively rules out monkeypox infection r10
    • Though rash typically follows fever and other prodromal symptoms in classic endemic monkeypox, rash may be the first or only symptom in 2022 outbreak cases r11r12r13r14
    • Initial rash on face is frequently described in endemic monkeypox cases; initial lesions in mucosal regions (oral, genital, perianal) have been more common in 2022 outbreak cases, and proctitis is possible as well r14r15r28
    • CDC has issued a health advisory urging clinicians to be vigilant for rash that may be consistent with monkeypox, 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 r15
    • Clinicians should undertake a thorough skin and mucosal (oral, genital, perianal) examination for characteristic lesions in patients presenting with potential monkeypox; this examination allows detection of lesions that the patient may not have been aware of r28
    • May be macular, papular, vesicular, or pustular; lesions evolve through this sequence before scabbing over and falling off
    • 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 outbreak cases r25r27
    • 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

  • Monkeypox 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
    • Monkeypox virus is the foremost orthopoxvirus affecting humans since the global eradication of smallpox r29r30
    • Natural reservoir of monkeypox virus is unknown; despite the name, rodents and other small mammals are implicated much more frequently than monkeys or other primates
    • 2 distinct monkeypox virus genetic groups (clades) have been characterized: West African and Central African; the ongoing 2022 outbreak appears to originate from the West African clade, which is associated with milder disease r1r13r31
  • Transmission is via contact with an infected person or animal, or other materials contaminated with the virus r32
    • Virus is believed to enter body via broken skin, mucous membranes, or respiratory tract r1
    • Human to human transmission is primarily through direct or indirect contact with monkeypox lesions, lesion material, respiratory secretions, other bodily fluids, and contaminated surfaces or materials (eg, dishes, utensils, clothing, bedding, linens) r1
    • Direct skin to skin contact, including intimate and sexual contact, has been identified as the primary mode of exposure and transmission in 2022 outbreak cases r33r34
    • Vertical transmission from mother to fetus via the placenta during pregnancy is possible r32
    • Unknown at this time whether semen, vaginal fluids, urine, and feces can propagate infection r32
    • 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 outbreak cases tend to occur at younger ages
    • Median patient age in the United States is 35 years r11
    • Median patient age worldwide is 37 years; patients aged 18 to 44 years account for 77% of cases r7r9
Sex
  • For 2022 outbreak cases with available sex data, over 98% of cases in the United States, and 99% worldwide, have been in males r7r27
Ethnicity/race
  • For 2022 outbreak cases in the United States with ethnicity/race data reported to CDC, 38% of patients are White, 26% are Black, and 32% are Hispanic; data are missing for many cases
Other risk factors/associations
  • Sexual activity, especially male to male sexual contact r14r15r35r36
    • Most cases in the ongoing 2022 outbreak 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 history of male to male sexual contact was self-reported in 98.4% of male patients in US cases for which such data was available, per CDC data r11
      • Per WHO data, among cases worldwide with reported sexual orientation, 98% of patients identified as gay or bisexual or other men who have sex with men r7
      • The largest case series to date for the 2022 outbreak, reporting on 528 cases in 16 countries, similarly found that 98% of cases were in gay or bisexual men, with sexual activity implicated in transmission in 95% of persons with infection r34
    • History of multiple casual sexual encounters or multiple sexual partners further increases risk of exposure and infection r25
    • Monkeypox 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 r33
  • Sexually transmitted infections
    • Concomitant sexually transmitted infections were reported in 29% of patients diagnosed with monkeypox in a recent large, international case series r34
  • HIV
    • Among 2022 outbreak cases with reported HIV status, 41% of cases worldwide have been positive for HIV; rates in individual countries have ranged from 30% to 51% r7r37
    • Unknown at this time whether HIV per se increases risk of monkeypox infection r37
  • Health care workers r20
    • Health care workers are at risk of monkeypox 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
  • General public r19
    • Personal and household contacts are also at risk of monkeypox infection via direct and indirect contact with monkeypox lesions, lesion material, respiratory secretions, other bodily fluids, and contaminated surfaces or materials (eg, dishes, utensils, clothing, bedding, linens)

Diagnostic Procedures

Primary diagnostic tools

  • Monkeypox is diagnosed via laboratory detection of monkeypox virus in the setting of appropriate epidemiologic risk factors and clinical findings
  • CDC has defined a confirmed monkeypox case as: r10
    • Criteria met for suspect case and
    • Monkeypox infection confirmed by one of the following:
      • Detection of monkeypox virus DNA by polymerase chain reaction testing or gene sequencing or
      • Isolation of monkeypox virus in culture from a clinical specimen
    • Suspect case
      • New rash characteristic of monkeypox or
      • Meets one epidemiologic criterion within 21 days of symptom onset and high clinical suspicion for monkeypox exists
    • Epidemiologic criteria
      • Contact with another case or cases with a similar rash or diagnosis of confirmed or probable monkeypox or
      • Close or intimate in-person contact with persons in a social network experiencing monkeypox activity, such as men who have sex with men or
      • Travel outside the United States to a country with confirmed monkeypox or where monkeypox 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 monkeypox virus or antibodies
  • For the ongoing 2022 monkeypox outbreak, 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 monkeypox unless proven otherwise r14
  • WHO has also published interim guidance for monkeypox surveillance, reporting, case investigation, and contact tracing, for international application r26

Laboratory

  • Specific diagnostic tests
    • Possible cases of monkeypox 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) r14
    • 2 tests are currently in use to establish presence of monkeypox infection; either or both may be used: r11
      • 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
        • At this time, all confirmed orthopox cases in the United States are presumed to be monkeypox unless proven otherwise, as there are no other clinically significant orthopoxviruses in circulation r11
        • Once an orthopox case is confirmed, laboratories may forward specimens to CDC for further monkeypox-specific viral characterization and sequencing
      • Certain authorized commercial laboratories and CDC can perform monkeypox-specific real-time polymerase chain reaction testing on lesion material; testing detects the presence of monkeypox DNA, and a positive result establishes a confirmed monkeypox case
        • Authorized commercial laboratories can perform this as initial testing, while CDC performs this 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 monkeypox 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 r10r14r29
    • CDC recommends that swabs be collected for testing if: r27
      • Classic monkeypox rash is present or
      • Potential monkeypox rash is present and patient has epidemiologic risk factors as defined in CDC case definition (ie, contact with someone with similar rash or confirmed monkeypox diagnosis, close contact with people in a social network with monkeypox activity, history of recent international travel to country with confirmed cases)
    • Specimens should be collected with use of appropriate personal protective equipment, including gown, gloves, eye protection, and N95-comparable or higher-level respirator r16
    • Specimen type r11
      • Testing performed at Laboratory Response Network laboratories, authorized commercial laboratories, and CDC is performed on lesion material from swabs; specific requirements for specimen collection may vary r11r16
      • At least 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
    • 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 r16r38
    • Complete information for specimen submission to CDC is available on the CDC website: r16r38
      • Dry swab of lesion surface or lesion fluid is acceptable
      • Synthetic swabs (eg, polyester, nylon, or Dacron) with plastic, wood, or thin aluminum shafts should be used; cotton swabs may interfere with PCR testing and should not be used
      • 2 swabs from each lesion should be sampled; lesions from different parts of the body or with different morphologic appearances in particular should be sampled
      • Specimens should be frozen (−20 °C or lower) within an hour of collection; frozen samples can be stored for up to 60 days
      • Transport media should not be added
      • Turnaround time for CDC testing is 5 days
    • WHO has also published interim guidance for laboratory testing for monkeypox virus, for international application r39

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 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
      • 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 r3
      • Other orthopoxviruses that can cause disease in humans include the causative agents of smallpox, vaccinia, and cowpox
      • Overall clinical course and features of monkeypox are quite similar to those of smallpox, which has been eradicated globally and is no longer seen r13r29
      • Lymphadenopathy is frequently present in monkeypox but absent in smallpox r12r13
      • 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 monkeypox-specific polymerase chain reaction testing to differentiate monkeypox from other orthopoxviruses; however, CDC states there are no other clinically significant orthopoxviruses in circulation in the United States at this time r11

Treatment

Goals

  • Supportive care for all patients; supportive care alone suffices for many patients with monkeypox
  • Management of symptoms depending on affected systems or specific syndromes
  • Antiviral treatment to ameliorate severe disease and reduce risk for patients with high risk of severe disease or high-risk disease features

Disposition

Admission criteria

  • Patients with mild disease can be managed at home, with appropriate isolation and infection control precautions in place
  • Admission is likely warranted for the same patient groups who may be considered for antiviral therapy:
    • Patients with severe disease
    • Patients at high risk of severe disease, such as those with significant immunocompromise or certain preexisting skin conditions, children, pregnant or breastfeeding adults, or those with significant disease-related complications
    • Patients with infection involving high-risk anatomic areas (eg, eyes, mouth, genitals, anus)
  • CDC states that the few monkeypox-related hospitalizations in the United States thus far have been primarily for pain management r27
  • Hospitalization rates around 10% have been reported internationally for the 2022 outbreak, with pain management and treatment of secondary bacterial infections the most commonly reported reasons r34r40

Recommendations for specialist referral

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

Treatment Options

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

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

  • Respiratory tract
    • Suctioning, incentive spirometry, chest physiotherapy, bronchodilators, antibiotics for secondary respiratory infections, nebulizer treatments, bronchoscopy, noninvasive ventilation, intubation/ventilation
  • Sepsis
    • Antibiotics, IV fluids, vasopressors, supplemental oxygen
  • Mucosal lesions
    • Mucosal care and analgesic medications
  • Vomiting/diarrhea
    • Oral or IV hydration and antiemetic/antidiarrheal medications
  • Fever
    • Antipyretic medications and external cooling measures
  • Skin compromise
    • Cleaning, moist dressings, topical antibiotics, surgical debridement, skin grafts
  • Secondary skin infection
    • Antibiotics, incision and drainage, advanced wound management
  • Inflammation/lymphadenopathy
    • Antiinflammatory and analgesic medications
  • Ocular infection
    • Ophthalmic antibiotics, antivirals, and corticosteroids; comprehensive ophthalmic evaluation including slitlamp examination

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

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

Currently there are no treatments approved specifically for monkeypox virus infection, but several antiviral agents originally developed for treatment of smallpox and other viral infections may be considered and obtained from the Strategic National Stockpile upon request from state health authorities after consultation with CDC; efficacy data for these agents is lacking owing to infeasibility of human smallpox experimentation r17r18

  • Tecovirimat r42
    • Approved for treatment of human smallpox disease in adults and children weighing at least 3 kg
    • Demonstrated efficacy against a diverse range of orthopoxviruses per in vitro and in vivo animal studies r43
    • CDC has an EA-IND protocol (expanded access–investigational new drug) that allows use in treatment of monkeypox in an outbreak
    • Instructions on obtaining and using tecovirimat, as well as required forms, are available at the CDC website r44
    • Available in capsule and injection form
    • Injection is contraindicated in severe renal impairment
  • Cidofovir r45
    • Originally approved for treatment of cytomegalovirus in patients with AIDS; has been used for other viral infections
    • CDC has an EA-IND protocol that allows use in treatment of monkeypox in an outbreak
    • IV infusion; must be administered with probenecid
    • BLACK BOX WARNINGS for renal impairment and neutropenia
    • Contraindicated in patients with severe renal impairment, those receiving potentially nephrotoxic agents, and those with hypersensitivity to cidofovir or severe hypersensitivity to probenecid or other sulfa-containing medications
  • VIGIV (vaccinia immune globulin intravenous) r46
    • Approved for treatment of complications due to vaccinia vaccination
    • CDC has an EA-IND protocol that allows use in treatment of monkeypox in an outbreak
    • For IV use only
    • BLACK BOX WARNING for interactions with glucose monitoring systems
      • Measure blood glucose with a glucose-specific method during VIGIV therapy; VIGIV contains maltose and may falsely elevate glucose readings with some types of glucose monitoring systems
    • Contraindicated in patients with history of anaphylaxis or other severe reaction to IV immune globulin, and in IgA-deficient patients with anti-IgA antibodies and history of IgA hypersensitivity
  • Brincidofovir r47
    • Approved for treatment of human smallpox disease in adults and children, including neonates
    • CDC is currently developing an EA-IND protocol to facilitate use in treatment of monkeypox; not currently available from the Strategic National Stockpile at this time
    • Available in tablet and oral suspension form
    • BLACK BOX WARNING for increased mortality risk when used for prolonged durations
    • No contraindications noted in prescribing information

Drug therapy

  • There are no treatments approved specifically for monkeypox; dosing recommendations are based on approved uses in smallpox or other viral infections
  • Antivirals
    • Tecovirimat r17r42
      • Oral
        • Administer within 30 minutes after a full meal containing moderate or high fat (approximately 600 calories and 25 grams of fat)
        • Capsules may be opened and mixed with 30 mL of liquid or soft food for patients who cannot swallow capsules
        • Tecovirimat Oral capsule; Neonates, Infants, and Children weighing less than 13 kg: 200 mg PO every 12 hours for 14 days is the dose for children and adolescents weighing 13 to 24 kg. The CDC EA-IND protocol notes that capsules may be opened and contents mixed with semi-solid food for pediatric patients weighing less than 13 kg; however, specific dosing recommendations are not provided.
        • Tecovirimat Oral capsule; Children and Adolescents weighing 13 to 24 kg: 200 mg PO every 12 hours for 14 days.
        • Tecovirimat Oral capsule; Children and Adolescents weighing 25 to 39 kg: 400 mg PO every 12 hours for 14 days.
        • Tecovirimat Oral capsule; Children and Adolescents weighing 40 to 119 kg: 600 mg PO every 12 hours for 14 days.
        • Tecovirimat Oral capsule; Children and Adolescents weighing 120 kg or more: 600 mg PO every 8 hours for 14 days.
        • Tecovirimat Oral capsule; Adults weighing 40 to 119 kg: 600 mg PO every 12 hours for 14 days.
        • Tecovirimat Oral capsule; Adults weighing 120 kg or more: 600 mg PO every 8 hours for 14 days.
      • Intravenous
        • Transition patients to oral therapy to complete the 14-day treatment course as soon as oral therapy is tolerated
        • Tecovirimat Solution for injection; Neonates, Infants, Children, and Adolescents weighing 3 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.
        • Tecovirimat Solution for injection; Children and Adolescents weighing 120 kg or more: 300 mg IV every 12 hours for 14 days.
        • Tecovirimat Solution for injection; Adults weighing 35 to 119 kg: 200 mg IV every 12 hours for 14 days.
        • Tecovirimat Solution for injection; Adults weighing 120 kg or more: 300 mg IV every 12 hours for 14 days.
    • Cidofovir r17r48
      • 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 is the FDA-approved induction dose for patients with cytomegalovirus retinitis.
    • Brincidofovir r17r49
      • CDC does not have an EA-IND protocol for brincidofovir for monkeypox, but it is currently developing one, to facilitate use
      • Administer on an empty stomach
      • Brincidofovir Oral suspension; Neonates: 6 mg/kg/dose PO once weekly for 2 weeks (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 weeks (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 weeks (on days 1 and 8).
      • Brincidofovir Oral suspension; Children and Adolescents weighing 48 kg or more: 200 mg PO once weekly for 2 weeks (on days 1 and 8).
      • Brincidofovir Oral suspension; Adults weighing less than 48 kg: 4 mg/kg/dose PO once weekly for 2 weeks (on days 1 and 8).
      • Brincidofovir Oral tablet; Adults weighing 48 kg or more: 200 mg PO once weekly for 2 weeks (on days 1 and 8).
  • Probenecid r48
    • 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 r17r50
    • Human Vaccinia Virus Immune Globulin Solution for injection; Adults: 6,000 units/kg/dose IV as soon as symptoms appear; may consider repeat dosing depending on symptom severity and treatment response and 9,000 units/kg/dose in patients not responding to the initial dose.

Comorbidities

  • HIV r37r51
    • Patients with advanced or uncontrolled HIV are at higher risk of severe or complicated monkeypox infection and prolonged monkeypox symptoms; effective antiretroviral therapy appears to attenuate risk
    • Unclear at this time whether monkeypox differentially infects people with and without HIV
    • Antiretroviral therapy and prophylaxis for opportunistic infections should be continued in all patients with HIV who develop monkeypox
    • Signs and symptoms of monkeypox 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)
    • Monkeypox vaccination considerations, antiviral treatments, and monitoring for patients with HIV should account for viral suppression and CD4 count in weighing risk of severe outcomes from monkeypox
    • Assessment for drug interactions between available antiviral treatments for monkeypox and antiretroviral therapy for HIV is advised
    • 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

Special populations

  • Pregnant or breastfeeding adults r52
    • Limited data exist regarding monkeypox in pregnancy; unclear if pregnancy increases risk of infection or more severe outcomes, though pregnant and breastfeeding patients are still considered a priority group for antiviral treatment
    • Adverse pregnancy outcomes, including fetal loss, have been reported in patients with monkeypox infection during pregnancy
    • Signs and symptoms of monkeypox are similar in pregnant and nonpregnant patients
    • If antiviral treatment is felt to be indicated, following consultation with CDC, 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, while cidofovir and brincidofovir showed evidence of teratogenicity
    • 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 monkeypox should not breastfeed and should not have direct skin-to-skin contact with infants until criteria for discontinuation of isolation for monkeypox have been met
  • Children and adolescents r53
    • Limited data exist regarding whether children have higher risk of monkeypox infection or different clinical outcomes compared with adults
    • Data from endemic monkeypox cases suggest higher risk of severe disease in children younger than 8 years and in those with preexisting immunocompromise or certain skin conditions
    • Signs and symptoms of monkeypox are similar in pediatric and adult patients
    • If antiviral treatment is judged to be indicated, after consultation with CDC, priority groups for treatment include children with:
      • Severe disease
      • Significant disease-related complications
      • History of immunocompromise, atopic dermatitis, or other active exfoliative skin conditions
      • Infection involving high-risk anatomic areas (eg, eyes, mouth, genitals, anus)
    • Tecovirimat is first-line antiviral treatment for children and adolescents; other treatments, including cidofovir, brincidofovir, and VIGIV, can be considered, but should be used with caution
    • No vaccines are currently licensed specifically for monkeypox prevention in children or adolescents; Jynneos vaccine can be offered for pediatric cases under an FDA emergency use authorization, following consultation with jurisdictional health authorities and CDC r54
      • No significant adverse events have been reported to date in infants and children who have received Jynneos vaccine
      • Pediatric data is 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 replicating vaccinia virus, was used for smallpox prevention up through the early 1970s
    • VIGIV and tecovirimat can also be considered for use as monkeypox postexposure prophylaxis through EA-IND authorization if vaccines are otherwise contraindicated; effectiveness of these medications as postexposure prophylaxis is unknown

Complications and Prognosis

Complications

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

Prognosis

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

Screening and Prevention

Prevention

  • General infection control measures r55r56
    • Avoid close, skin-to-skin contact, including intimate or sexual contact, with anyone that has a monkeypox-like rash r35
    • Avoid contact with potentially infected animals or animal products
    • Avoid contact with items or materials that have been in contact with sick animals or people
    • Isolate infected patients
    • Appropriate hand hygiene
    • Use appropriate personal protective equipment when caring for patients or collecting specimens for diagnosis
  • Infection control in health care settings r20
    • Regarding prevention of monkeypox transmission in health care settings, CDC references 2007 guidelines for preventing transmission of infectious agents in these settings r57
    • Patients with suspected or confirmed monkeypox infection should be placed in single-person rooms with standard precautions; special air handling is not necessary unless high-risk procedures are performed
    • Visitation should be limited to that which is necessary for patient care and wellbeing
    • Intubation, extubation, and any high-risk procedures likely to spread oral secretions should be performed in airborne isolation rooms
    • Personal protective equipment for health care staff entering the patient's room should include gown, gloves, eye protection, and N95-comparable or higher-level respirator
    • Waste management should be performed in accordance with hazardous materials regulations
    • Soiled laundry should be managed in accordance with recommended standard practices for environmental infection control r58
    • Cleaning and disinfection should be performed using hospital-grade disinfectant with an emerging viral pathogen claim
    • Wet cleaning methods are preferred; dry dusting, sweeping, and vacuuming should be avoided
    • Infection control precautions should be maintained until all lesions have scabbed off, separated, and healed with a fresh layer of intact skin, or until cleared by public health authorities r33
  • Infection control in home settings r19
    • Isolation and personal protective equipment
      • Patients who do not require hospital admission may isolate at home
      • Patients should not leave the home except for emergencies or necessary medical care
      • Visitors should refrain from visiting during the isolation period
      • Patients should isolate separately from and avoid close contact with other household members and pets; patients and household members should both wear medical masks when close contact is necessary or cannot be avoided
      • A separate bathroom should be used if possible
      • Patients should manage their own wound care, linens, and laundry if possible, using disposable gloves and appropriate hand hygiene; if assistance from household members is required, disposable medical gloves and a medical mask should be used
      • Skin lesions should be covered as much as much as possible, with long sleeves, long pants, and gloves
      • Patients should avoid use of contact lenses and shaving rash-covered areas to prevent further spread of lesions
    • Hand hygiene and household disinfection
      • Potentially contaminated personal items, such as clothing, linens, towels, dishes, and utensils, should be washed properly and not shared
      • Frequently touched surfaces, such as counters and light switches, should be regularly cleaned and disinfected
      • Hand hygiene, with an alcohol-based hand rub or soap and water, should be performed after any contact with rash material or potentially contaminated materials and surfaces
      • If use of a separate bathroom is not possible, potentially contaminated surfaces should be cleaned and disinfected after each use of the shared space
      • CDC has published detailed interim guidance for household disinfection of monkeypox r59
    • Sexual activity
      • Patients should refrain from all sexual activity during the isolation period r24
      • Barrier practices (eg, condoms) are recommended after recovery; data to guide duration are sparse, but some countries recommend at least 8 weeks r24
    • Infection control precautions should be maintained until all lesions have scabbed off, separated, and healed with a fresh layer of intact skin, or until cleared by public health authorities r33
  • Exposure management
    • Monitoring people who have been exposed r21
      • Notify public health authorities when monitoring of exposed contacts is undertaken r14
      • Exposure risk assessment should be performed to determine possible need for postexposure prophylaxis
      • People with confirmed exposure to monkeypox should monitor for the following symptoms for 21 days after last exposure:
        • Fever of 38 °C or higher
        • Chills
        • New lymphadenopathy
        • New rash
      • Asymptomatic contacts can continue routine daily activities during the monitoring period but should not donate blood, bodily fluids, cells, tissues, or organs during that period
      • If fever or rash develop, contacts should self-isolate and contact their local or state health department for further instructions
      • If chills or lymphadenopathy develop, contacts should isolate at home for 24 hours and monitor for emergence of fever or rash; the health department should be contacted for further instructions if these develop
    • Monitoring exposed health care professionals r21
      • Public health authorities should be notified when monitoring is undertaken of health care personnel; infection control can facilitate necessary reporting in the hospital setting r14
      • Exposure risk assessment should be performed to determine possible need for postexposure prophylaxis
      • Any health care workers who have cared for patients with monkeypox should monitor for possible symptoms of monkeypox, especially within 21 days of contact
      • Health care workers with unprotected exposures may continue to work, but they should measure temperatures at least twice daily for 21 days after exposure and be assessed for new fever or rash before work each day during this period
    • Exposure risk assessment and postexposure prophylaxis r21
      • Exposure risk assessment for all persons with potential monkeypox exposure should be performed to determine need for postexposure prophylaxis
      • Management recommendations depend on degree of exposure:
        • High-risk: symptom monitoring; postexposure prophylaxis with ACAM2000 or Jynneos vaccination is recommended
          • High-risk exposures include:
            • Unprotected contact between a person's skin or mucous membranes and the skin, lesions, bodily fluids, or contaminated materials from a patient or
            • Being inside the patient's room or within 6 feet of a patient during aerosol-generating procedures without wearing an N95-comparable or higher-level respirator and eye protection or
            • Other exposures determined by public health authorities to be at this level
        • Intermediate-risk: symptom monitoring; need for postexposure prophylaxis can be determined on an individual basis
          • Intermediate-risk exposures include:
            • Being within 6 feet for 3 hours or more of an unmasked patient without wearing at least a surgical mask or
            • Contact between sleeves or other clothing and the patient's skin, lesions, bodily fluids, or contaminated materials or
            • Other exposures determined by public health authorities to be at this level
        • Low/uncertain-risk: symptom monitoring recommended; postexposure prophylaxis not indicated
          • Low/uncertain-risk exposures include:
            • Entering the patient's room without eye protection regardless of duration or
            • Gown, gloves, eye protection, and at least surgical mask worn for all entries into the patient's room or
            • Being within 6 feet of an unmasked patient for less than 3 hours without wearing at least a surgical mask or
            • Other exposures determined by public health authorities to be at this level
        • No risk: neither symptom monitoring nor postexposure prophylaxis indicated
          • These are exposures determined by public health authorities as not meeting criteria for other categories
  • Preexposure prophylaxis
    • One vaccine, Jynneos, is licensed in the United States for the prevention of monkeypox and smallpox; another, ACAM2000, is licensed for the prevention of smallpox but is considered effective for the prevention of monkeypox as well; although there are not yet robust vaccine efficacy data for the current outbreak, efficacy is estimated to be over 85%, based on prior data from Africa, as well as immunologic and animal studies r22r23
    • Advisory Committee on Immunization Practices (of CDC) has recommended use of Jynneos or ACAM2000 for preexposure vaccination of certain laboratory and health care personnel at ongoing risk for occupational exposure to orthopoxviruses, including: r60
      • Research laboratory personnel
      • Clinical laboratory personnel performing diagnostic testing for orthopoxviruses
      • Designated response team members
      • Health care personnel who administer ACAM2000 or care for patients for patients infected with orthopoxviruses
    • Vaccines for preexposure prophylactic vaccination can be obtained from CDC Drug Service after consultation with CDC Emergency Operations Center (telephone, 1-770-488-7100) r14
    • It is unclear how much protection against monkeypox is conferred by previous smallpox vaccination; CDC recommends following the same vaccination schedules as for those not previously vaccinated r23
  • Postexposure prophylaxis
    • Vaccines are effective in preventing disease before monkeypox exposure, and it is believed that they may prevent or ameliorate disease after exposure as well r22
    • Recommended for postexposure prophylaxis in persons with high-risk exposures and can be considered on an individual basis for persons with intermediate-risk exposures r21
    • Vaccination within 4 days of exposure is recommended to prevent disease r22
    • Vaccination between 4 and 14 days after exposure may reduce disease severity but may not prevent disease r22
    • Vaccines for postexposure prophylaxis can be obtained from the Strategic National Stockpile via CDC; requests should be initiated through state or territorial health authorities, but CDC Emergency Operations Center (telephone, 1-770-488-7100) is available for consultations to assist with appropriate vaccine use r14
    • For the 2022 outbreak event, some public health jurisdictions are employing an expanded approach to postexposure prophylaxis, offering vaccination to individuals at increased risk of recent monkeypox exposure, even without documented exposure to someone with confirmed monkeypox r22r23
    • Current vaccination efforts in the 2022 outbreak response in the United States are primarily deploying Jynneos vaccine; any consideration of ACAM2000 should be made in consultation with CDC r23
    • CDC is currently allocating Jynneos vaccine to public health jurisdictions for use in: r23
      • Known monkeypox contacts identified through case investigation, contact tracing, and risk exposure assessments
      • Presumed monkeypox contacts with:
        • A sexual partner in the past 14 days diagnosed with monkeypox
        • Multiple sexual partners in the past 14 days in a jurisdiction with known monkeypox
    • Other agents for postexposure prophylaxis r11r53
      • Though clinical efficacy is unknown, VIGIV and tecovirimat may be considered for use as monkeypox postexposure prophylaxis in certain limited circumstances if vaccines are contraindicated (eg, severe allergy to vaccine components)
      • Any such use must be in clinical consultation with CDC
  • Vaccines
    • Jynneos r23r61
      • Approved for prevention of smallpox and monkeypox disease in patients aged 18 years or older who are determined to be at high risk for infection; FDA has issued an emergency use authorization for use in the prevention of monkeypox disease in patients younger than 18 years r54
      • Nonreplicating live virus (vaccinia) preparation
      • Completion of standard regimen requires 2 subcutaneous injections 4 weeks apart; vaccination is considered complete 2 weeks after the second dose r22
      • As a means of increasing available vaccine supply, an alternative regimen via intradermal administration may be used for patients aged 18 years or older under an FDA emergency use authorization; intradermal and subcutaneous routes of administration elicited similar immune responses in clinical studies r54r62
        • CDC states that when necessary, a person aged 18 years or older who received 1 Jynneos vaccine dose with the standard subcutaneous regimen may receive a second dose with the alternative intradermal regimen at the recommended interval to complete the series
      • Although some domestic and international jurisdictions are delaying the second dose, or employing a "1 dose only" strategy because of supply limitations, CDC states that 2 doses are required for most patients, as this is the only FDA-approved regimen r23
        • Recommended interval between the 2 doses of vaccine is at least 4 weeks; doses may be up to 5 weeks apart r63
          • If the second dose is not administered within the recommended interval, it should be administered as soon as possible; there is no need to restart the regimen or add doses if the dosing interval is extended r63
      • CDC is collecting data on Jynneos vaccine efficacy in the 2022 outbreak
      • Preferred vaccine for most patients in whom vaccination is indicated, including patients with HIV, pregnant or breastfeeding patients, and pediatric patients r37r52r53
        • Elicited higher peak neutralizing antibody titers against smallpox compared with ACAM2000 in clinical trials, with better safety profile r64
        • Less potential for adverse events compared with ACAM2000 vaccine r22
        • Can be used in certain immunocompromised patients in whom ACAM2000 vaccine is contraindicated r64
      • Generally well-tolerated, with few adverse reactions noted in clinical studies r60
      • Warnings listed for severe allergic reactions (including anaphylaxis) and diminished response in immunocompromised patients
      • Preexposure prophylaxis r61
        • Subcutaneous
          • Modified Vaccinia Ankara Suspension for injection; Infants, Children, and Adolescents: 0.5 mL subcutaneously for 2 doses administered 4 weeks apart.
          • Modified Vaccinia Ankara Suspension for injection; Adults: 0.5 mL subcutaneously for 2 doses administered 4 weeks apart.
        • Intradermal
          • Modified Vaccinia Ankara Suspension for injection; Adults: 0.1 mL intradermally for 2 doses administered 4 weeks apart.
      • Postexposure prophylaxis r22r61
        • Subcutaneous
          • Modified Vaccinia Ankara Suspension for injection; Infants, Children, and Adolescents: 0.5 mL subcutaneously for 2 doses administered 4 weeks apart. Administer within 4 days from exposure date to prevent onset of disease. If administered between 4 and 14 days after exposure, vaccination may reduce symptoms of disease, but not prevent disease.
          • Modified Vaccinia Ankara Suspension for injection; Adults: 0.5 mL subcutaneously for 2 doses administered 4 weeks apart. Administer within 4 days from exposure date to prevent onset of disease. If administered between 4 and 14 days after exposure, vaccination may reduce symptoms of disease, but not prevent disease. If it has been more than 3 years since vaccination, consider revaccinating.
        • Intradermal
          • Modified Vaccinia Ankara Suspension for injection; Adults: 0.1 mL intradermally for 2 doses administered 4 weeks apart. Administer within 4 days from exposure date to prevent onset of disease. If administered between 4 and 14 days after exposure, vaccination may reduce symptoms of disease, but not prevent disease. If it has been more than 3 years since vaccination, consider revaccinating.
    • ACAM2000 r65
      • Approved for active immunization against smallpox disease in persons aged 16 years or older determined to be at high risk for infection
      • CDC-held EA-IND protocol allows use for non-smallpox orthopoxvirus infection (eg, monkeypox) during an outbreak r27
      • Live preparation of vaccinia inoculated directly into skin via percutaneous scarification
      • Results in a localized viral inoculation lesion; vaccinia can progress and spread in the vaccine recipient, and it can even be transmitted to close contacts and result in clinically significant infection
      • Greater potential for serious adverse events compared with Jynneos vaccine
      • Contraindicated in severe immunodeficiency, owing to possible severe localized or systemic vaccinia infection
      • Contraindicated in patients with HIV (regardless of immune status) and pregnant or breastfeeding patients; Jynneos vaccine is preferred in pediatric populations when vaccination is indicated r37r52r53
      • BLACK BOX WARNING for numerous rare complications potentially resulting in severe disability, permanent impairment, and death, including myocarditis and pericarditis, encephalitis, encephalopathy, progressive or generalized vaccinia, severe skin infections or reactions, ocular complications, blindness, and fetal death
      • Preexposure prophylaxis r65
        • Vaccinia Virus Strain New York City Board of Health Live Antigen Solution for percutaneous scarification; Adolescents 16 to 17 years: 0.0025 mL (a droplet of vaccine) administered percutaneously onto the arm by rapidly making 15 needle punctures. If a major reaction is not obtained 6 to 8 days after vaccination, check vaccination procedures, and repeat vaccination with vaccine from another vial or vaccine lot, if available. If a repeat vaccination using vaccine from another vial or vaccine lot fails to produce a major reaction, consult CDC or state or local health department before giving another vaccination. Patients who are at continued high risk of monkeypox exposure may be revaccinated every 3 years. For booster vaccination, make 15 needle punctures. There may be a reduced cutaneous response to revaccination; do not revaccinate.
        • Vaccinia Virus Strain New York City Board of Health Live Antigen Solution for percutaneous scarification; Adults: 0.0025 mL (a droplet of vaccine) administered percutaneously onto the arm by rapidly making 15 needle punctures. If a major reaction is not obtained 6 to 8 days after vaccination, check vaccination procedures, and repeat vaccination with vaccine from another vial or vaccine lot, if available. If a repeat vaccination using vaccine from another vial or vaccine lot fails to produce a major reaction, consult CDC or state or local health department before giving another vaccination. Patients who are at continued high risk of monkeypox exposure may be revaccinated every 3 years. For booster vaccination, make 15 needle punctures. There may be a reduced cutaneous response to revaccination; do not revaccinate.
      • Postexposure prophylaxis r22r65
        • Vaccinia Virus Strain New York City Board of Health Live Antigen Solution for percutaneous scarification; Adolescents 16 to 17 years: 0.0025 mL (a droplet of vaccine) administered percutaneously onto the arm by rapidly making 15 needle punctures. Administer within 4 days from exposure date to prevent onset of disease. If administered between 4 and 14 days after exposure, vaccination may reduce symptoms of disease, but not prevent disease. If it has been more than 3 years since vaccination, consider revaccinating. If a major reaction is not obtained 6 to 8 days after vaccination, check vaccination procedures, and repeat vaccination with vaccine from another vial or vaccine lot, if available. If a repeat vaccination using vaccine from another vial or vaccine lot fails to produce a major reaction, consult CDC or state or local health department before giving another vaccination. There may be a reduced cutaneous response to revaccination; do not revaccinate.
        • Vaccinia Virus Strain New York City Board of Health Live Antigen Solution for percutaneous scarification; Adults: 0.0025 mL (a droplet of vaccine) administered percutaneously onto the arm by rapidly making 15 needle punctures. Administer within 4 days from exposure date to prevent onset of disease. If administered between 4 and 14 days after exposure, vaccination may reduce symptoms of disease, but not prevent disease. If it has been more than 3 years since vaccination, consider revaccinating. If a major reaction is not obtained 6 to 8 days after vaccination, check vaccination procedures, and repeat vaccination with vaccine from another vial or vaccine lot, if available. If a repeat vaccination using vaccine from another vial or vaccine lot fails to produce a major reaction, consult CDC or state or local health department before giving another vaccination. There may be a reduced cutaneous response to revaccination; do not revaccinate.
    • WHO has also published interim guidance on vaccines and immunization for monkeypox, for international application; WHO and CDC recommendations are largely congruent r66
Petersen E et al: Human monkeypox: epidemiologic and clinical characteristics, diagnosis, and prevention. Infect Dis Clin North Am. 33(4):1027-43, 201930981594WHO: Monkeypox Fact Sheet. WHO website. Published May 19, 2022. Accessed July 29, 2022. https://www.who.int/news-room/fact-sheets/detail/monkeypoxhttps://www.who.int/news-room/fact-sheets/detail/monkeypoxPetersen BW et al: Orthopoxviruses: vaccinia (smallpox vaccine), variola (smallpox), monkeypox, and cowpox. In: Bennett JE et al, eds: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020:1809-17.e3https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323482554001326?scrollTo=%23hl00005423-s2.0-B9780323482554001326hl0000542CDC: Monkeypox: About Monkeypox. CDC website. Reviewed July 22, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/about.htmlhttps://www.cdc.gov/poxvirus/monkeypox/about.htmlCDC: Monkeypox: U.S. Outbreak 2022: Situation Summary: Past U.S. Cases and Outbreaks. CDC website. Reviewed June 6, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/outbreak/us-outbreaks.htmlhttps://www.cdc.gov/poxvirus/monkeypox/outbreak/us-outbreaks.htmlHuhn GD et al: Clinical characteristics of human monkeypox, and risk factors for severe disease. Clin Infect Dis. 41(12):1742-51, 200516288398WHO: Multi-country Outbreak of Monkeypox, External Situation Report 2--25 July 2022. WHO website. Published July 25, 2022. Accessed July 29, 2022. https://www.who.int/publications/m/item/multi-country-outbreak-of-monkeypox--external-situation-report--2---25-july-2022https://www.who.int/publications/m/item/multi-country-outbreak-of-monkeypox--external-situation-report--2---25-july-2022CDC: Monkeypox: U.S. Monkeypox 2022: Situation Summary. CDC website. Updated July 28, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/response/2022/index.htmlhttps://www.cdc.gov/poxvirus/monkeypox/response/2022/index.htmlWHO: 2022 Monkeypox Outbreak: Global Trends. WHO website. Published 28, 2022. Accessed July 29, 2022. https://worldhealthorg.shinyapps.io/mpx_global/https://worldhealthorg.shinyapps.io/mpx_global/CDC: Monkeypox: Healthcare Professionals: Case Definitions for Use in the 2022 Monkeypox Response. CDC website. Updated July 22, 2022. Accessed August 1, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/case-definition.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/case-definition.htmlCDC: Clinician Outreach and Communication Activity (COCA): Monkeypox Outbreak: Updates on the Epidemiology, Testing, Treatment, and Vaccination. CDC website. Reviewed July 20, 2022. Accessed August 1, 2022. https://emergency.cdc.gov/coca/calls/2022/callinfo_072622.asphttps://emergency.cdc.gov/coca/calls/2022/callinfo_072622.aspCDC: Monkeypox: Signs and Symptoms. CDC website. Reviewed July 29, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/symptoms.htmlhttps://www.cdc.gov/poxvirus/monkeypox/symptoms.htmlCDC: Monkeypox: Healthcare Professionals: Clinical Guidance: Clinical Recognition. CDC website. Reviewed June 24, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.htmlCDC: Clinician Outreach and Communication Activity (COCA): What Clinicians Need to Know about Monkeypox in the United States and Other Countries. CDC website. Reviewed May 20, 2022. Accessed August 1, 2022. https://emergency.cdc.gov/coca/calls/2022/callinfo_052422.asphttps://emergency.cdc.gov/coca/calls/2022/callinfo_052422.aspCDC: Health Alert Network (HAN) No. 466: Monkeypox Virus Infection in the United States and Other Non-endemic Countries--2022. CDC website. Published May 20, 2022. Accessed July 29, 2022. https://emergency.cdc.gov/han/2022/han00466.asphttps://emergency.cdc.gov/han/2022/han00466.aspCDC: Monkeypox: Healthcare Professionals: Specimen Collection. CDC website. Reviewed July 29, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/prep-collection-specimens.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/prep-collection-specimens.htmlCDC: Monkeypox: Treatment. CDC website. Reviewed June 17, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/treatment.htmlhttps://www.cdc.gov/poxvirus/monkeypox/treatment.htmlCDC: Monkeypox: Healthcare Professionals: Clinical Guidance: Clinical Treatment. CDC website. Updated July 28, 2022. Accessed August 1, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.htmlCDC: Monkeypox: Healthcare Professionals: Infection Control: Home. CDC website. Reviewed June 16, 2022. Accessed August 1, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-home.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-home.htmlCDC: Monkeypox: Healthcare Professionals: Infection Control: Infection Control in Healthcare Settings. CDC website. Reviewed July 5, 2022. Accessed August 1, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.htmlCDC: Monkeypox: Healthcare Professionals: Clinical Guidance: Monitoring Persons Exposed. CDC website. Reviewed June 8, 2022. Accessed August 1, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/monitoring.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/monitoring.htmlCDC: Monkeypox: Healthcare Professionals: Monkeypox and Smallpox Vaccine Guidance. CDC website. Reviewed June 2, 2022. Accessed August 1, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/smallpox-vaccine.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/smallpox-vaccine.htmlCDC: Monkeypox: Considerations for Monkeypox Vaccination. CDC website. Updated July 28, 2022. Accessed August 1, 2022. https://www.cdc.gov/poxvirus/monkeypox/considerations-for-monkeypox-vaccination.htmlhttps://www.cdc.gov/poxvirus/monkeypox/considerations-for-monkeypox-vaccination.htmlCDC: Monkeypox: Healthcare Professionals: Clinician FAQs. CDC website. Updated July 5, 2022. Accessed August 2, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/faq.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/faq.htmlEuropean Centre for Disease Prevention and Control: Monkeypox multi-country outbreak--first update. ECDC website. Published July 8, 2022. Accessed August 2, 2022. https://www.ecdc.europa.eu/en/publications-data/monkeypox-multi-country-outbreak-first-updatehttps://www.ecdc.europa.eu/en/publications-data/monkeypox-multi-country-outbreak-first-updateWHO: Surveillance, Case Investigation, and Contact Tracing for Monkeypox: Interim Guidance. WHO website. Updated June 24, 2022. Accessed July 29, 2022. https://www.who.int/publications/i/item/WHO-MPX-surveillance-2022.1https://www.who.int/publications/i/item/WHO-MPX-surveillance-2022.1CDC: Clinician Outreach and Communication Activity (COCA): Monkeypox: Updates about Clinical Diagnosis and Treatment. CDC website. Reviewed June 24, 2022. Accessed August 2, 2022. https://emergency.cdc.gov/coca/calls/2022/callinfo_062922.asphttps://emergency.cdc.gov/coca/calls/2022/callinfo_062922.aspCDC: Health Alert Network (HAN) No. 468: Updated Case-finding Guidance: Monkeypox Outbreak—United States, 2022. CDC website. Published June 14, 2022. Accessed August 2, 2022. https://emergency.cdc.gov/han/2022/han00468.asphttps://emergency.cdc.gov/han/2022/han00468.aspMcCollum AM et al: Human monkeypox. Clin Infect Dis. 58(2):260-7, 201424158414Sklenovská N et al: Emergence of monkeypox as the most important orthopoxvirus infection in humans. Front Public Health. 6:241, 201830234087Guarner J et al: Monkeypox in 2022--what clinicians need to know. JAMA. 328(2):139-40, 202235696257CDC: Monkeypox: How It Spreads. CDC website. Updated July 29, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/transmission.htmlhttps://www.cdc.gov/poxvirus/monkeypox/transmission.htmlCDC: Monkeypox: Healthcare Professionals: Clinical Guidance: Isolation and Prevention Practices for People with Monkeypox. CDC website. Updated August 1, 2022. Accessed August 1, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/isolation-procedures.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/isolation-procedures.htmlThornhill JP et al: Monkeypox virus infection in humans across 16 countries--April-June 2022. N Engl J Med. ePub, 202235866746WHO: Monkeypox: Public Health Advice for Gay, Bisexual and Other Men Who Have Sex With Men. WHO website. Published May 25, 2022. Accessed July 29, 2022. https://www.who.int/news/item/25-05-2022-monkeypox--public-health-advice-for-gay--bisexual-and-other-men-who-have-sex-with-menhttps://www.who.int/news/item/25-05-2022-monkeypox--public-health-advice-for-gay--bisexual-and-other-men-who-have-sex-with-menCDC: Monkeypox: Prevention: Safer Sex, Social Gatherings, and Monkeypox. CDC website. Updated July 29, 2022. Accessed August 2, 2022. https://www.cdc.gov/poxvirus/monkeypox/sexualhealth/index.htmlhttps://www.cdc.gov/poxvirus/monkeypox/sexualhealth/index.htmlCDC: Monkeypox: Healthcare Professionals: Clinical Guidance: Considerations for People with HIV. CDC website. Updated July 21, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/people-with-HIV.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/people-with-HIV.htmlCDC: Infectious Diseases Laboratories: Test Order: Poxvirus Molecular Detection. CDC website. Reviewed July 25, 2022. Accessed July 29, 2022. https://www.cdc.gov/laboratory/specimen-submission/detail.html?CDCTestCode=CDC-10515https://www.cdc.gov/laboratory/specimen-submission/detail.html?CDCTestCode=CDC-10515WHO: Laboratory Testing for the Monkeypox Virus: Interim Guidance. WHO website. Published May 23, 2022. Accessed July 29, 2022. https://www.who.int/publications/i/item/WHO-MPX-laboratory-2022.1https://www.who.int/publications/i/item/WHO-MPX-laboratory-2022.1Girometti N et al: Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis. Lancet Infect Dis. ePub, 202235785793Reynolds MG et al: Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research. Viruses. 9(12), 201729231870SIGA Technologies Inc: TPOXX (tecovirimat): Highlights of Prescribing Information. FDA website. Revised May 2022. Accessed July 29, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214518s000lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214518s000lbl.pdfRusso AT et al: An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications. Expert Rev Anti Infect Ther. 19(3):331-44, 202132882158CDC: Monkeypox: Healthcare Professionals: Clinical Guidance: Information for Healthcare Providers on Obtaining and Using TPOXX (Tecovirimat) for Treatment of Monkeypox. CDC website. Updated July 22, 2022. Accessed August 1, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/obtaining-tecovirimat.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/obtaining-tecovirimat.htmlGilead Sciences Inc: Vistide (cidofovir injection). Prescribing Information. FDA website. Updated September 2000. Accessed July 29, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/020638s003lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/1999/020638s003lbl.pdfCangene Corp: CNJ-016, Vaccinia Immune Globulin Intravenous: Highlights of Prescribing Information. FDA website. Revised January 2010. Accessed July 29, 2022. https://www.fda.gov/media/78174/downloadhttps://www.fda.gov/media/78174/downloadChimerix Inc: Tembexa (brincidofovir): Highlights of Prescribing Information. FDA website. Revised June 2021. Accessed July 29, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214460s000,214461s000lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214460s000,214461s000lbl.pdfMylan Institutional LLC: Cidofovir injection solution. Package insert. Mylan Institutional LLC; April 2021Cambrex Whippany Inc: Tembexa (brincidofovir). Package insert. Cambrex Whippany Inc; August 2021Emergent BioSolutions Canada Inc: CNJ-016 (vaccinia immune globulin intravenous, human). Package insert. Emergent BioSolutions Canada Inc; November 2018US Department of Health and Human Services: Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. AIDSinfo website. Updated August 1, 2022. Accessed August 2, 2022. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/monkeypoxhttps://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/monkeypoxCDC: Monkeypox: Healthcare Professionals: Clinical Guidance: Pregnancy Considerations. CDC website. Updated July 18, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/pregnancy.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/pregnancy.htmlCDC: Monkeypox: Healthcare Professionals: Clinical Guidance: Pediatric Considerations. CDC website. Updated July 26, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/pediatric.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/pediatric.htmlBavarian Nordic A/S: Fact Sheet for Healthcare Providers Administering Vaccine: Emergency Use Authorization of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Non-replicating) for Prevention of Monkeypox Disease in Individuals Determined to be at High Risk for Monkeypox Infection. FDA website. Updated August 9, 2022. Accessed August 12, 2022. https://www.fda.gov/media/160774/downloadhttps://www.fda.gov/media/160774/downloadCDC: Monkeypox: Healthcare Professionals: Infection Control. CDC website. Updated June 30, 2022. Accessed August 2, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control.htmlhttps://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control.htmlCDC: Monkeypox: Prevention. CDC website. Reviewed July 29, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/prevention.htmlhttps://www.cdc.gov/poxvirus/monkeypox/prevention.htmlSiegel JD et al: 2007 guideline for isolation precautions: preventing transmission of infectious agents in health care settings. Am J Infect Control. 35(10 suppl 2):S65-164, 200718068815CDC: Guidelines for Environmental Infection Control in Health-Care Facilities. CDC website. Updated July 2019. Accessed August 2, 2022. https://www.cdc.gov/infectioncontrol/pdf/guidelines/environmental-guidelines-P.pdfhttps://www.cdc.gov/infectioncontrol/pdf/guidelines/environmental-guidelines-P.pdfCDC: Monkeypox: Interim Guidance for Household Disinfection of Monkeypox Virus. CDC website. Reviewed June 6, 2022. Accessed July 29, 2022. https://www.cdc.gov/poxvirus/monkeypox/pdf/Monkeypox-Interim-Guidance-for-Household-Disinfection-508.pdfhttps://www.cdc.gov/poxvirus/monkeypox/pdf/Monkeypox-Interim-Guidance-for-Household-Disinfection-508.pdfRao AK et al: Use of JYNNEOS (smallpox and monkeypox vaccine, live, nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices--United States, 2022. MMWR Morb Mortal Wkly Rep. 71(22):734-42, 202235653347Bavarian Nordic A/S: Jynneos (Smallpox and Monkeypox Vaccine, Live, Nonreplicating): Highlights of Prescribing Information. FDA website. Revised June 2021. Accessed July 29, 2022. https://www.fda.gov/media/131078/downloadhttps://www.fda.gov/media/131078/downloadFDA: News Release: Monkeypox Update: FDA Authorizes Emergency Use of JYNNEOS Vaccine to Increase Vaccine Supply. FDA website. Published August 9, 2022. Accessed August 12, 2022. https://www.fda.gov/news-events/press-announcements/monkeypox-update-fda-authorizes-emergency-use-jynneos-vaccine-increase-vaccine-supplyhttps://www.fda.gov/news-events/press-announcements/monkeypox-update-fda-authorizes-emergency-use-jynneos-vaccine-increase-vaccine-supplyCDC: Monkeypox: Health Departments: Vaccine Considerations: JYNNEOS Vaccine. Updated August 9, 2022. Accessed August 10, 2022. https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/jynneos-vaccine.htmlhttps://www.cdc.gov/poxvirus/monkeypox/interim-considerations/jynneos-vaccine.htmlPittman PR et al: Phase 3 efficacy trial of modified vaccinia Ankara as a vaccine against smallpox. N Engl J Med. 381(20):1897-908, 201931722150Emergent BioSolutions Inc: ACAM2000, (Smallpox (Vaccinia) Vaccine, Live): Highlights of Prescribing Information. FDA website. Revised March 2018. Accessed July 29, 2022. https://www.fda.gov/media/75792/downloadhttps://www.fda.gov/media/75792/downloadWHO: Vaccines and Immunization for Monkeypox: Interim Guidance. WHO website. Published June 14, 2022. Accessed July 29, 2022. https://www.who.int/publications/i/item/who-mpx-immunization-2022.1https://www.who.int/publications/i/item/who-mpx-immunization-2022.1
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