INTRODUCTION — Monkeypox virus is an orthopoxvirus that is in the same genus as variola virus (the causative agent of smallpox) and vaccinia virus (the virus used in smallpox vaccine). Patients with mpox (previously referred to as monkeypox) typically develop a rash that is similar in appearance to smallpox; however, the mortality from mpox is significantly less than for smallpox. The rash of mpox can also be similar in appearance to more common infectious rashes, such as those observed in secondary syphilis, herpes simplex infection, and varicella-zoster virus infection.
Prior to 2022, most cases of mpox occurred in Central and West Africa. However, an ongoing outbreak associated with person-to-person transmission, which was first reported in May 2022, has involved thousands of individuals in dozens of nonendemic countries.
This topic will review the treatment and prevention of mpox. Topic reviews that discuss the epidemiology, clinical manifestations, and diagnosis of mpox are presented separately. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)".)
TERMINOLOGY — In November 2022, the World Health Organization, who is responsible for naming and renaming of diseases under the International Classification of Diseases (ICD), changed the name of the disease referred to as "monkeypox" to "mpox" [1]. This change was made to follow current best practices of not naming diseases after animals or geographic locations and to reduce any stigma that could be associated with the original name.
The virus that causes mpox will continue to be referred to as monkeypox virus until the International Committee on the Taxonomy of Viruses (ICTV) officially decides what the name of the virus should be. However, the former Congo Basin (Central African) clade was renamed as Clade one (I) and the former West African clade was renamed as Clade two (II). Clade II consists of two subclades, IIa and IIb. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)", section on 'Virology'.)
CLINICAL MANAGEMENT — Management of patients with mpox involves supportive care as well as antiviral therapy for select patients.
Supportive care — Many patients with mpox have mild disease and will recover without medical intervention.
However, some patients may require pain relief medication (eg, for pain related to proctitis or tonsillitis). In addition, for conditions like proctitis, stool softeners, topical lidocaine, and/or sitz baths many need to be used. Guidance for pain management can be found on the United States Centers for Disease Control and Prevention (CDC) website.
Supportive care requiring hospitalization may be warranted for those who have or are at risk for dehydration (eg, nausea, vomiting, dysphagia, sever tonsillitis), those who require more intensive pain management, and those experiencing severe disease or complications.
Antiviral therapy — Several antivirals may be useful for the treatment of mpox. Some of these drugs were approved for treatment of smallpox based on animal models and dose and safety studies in healthy humans but are expected to have the same activity against mpox. At this time, tecovirimat is the treatment of choice. (See "Variola virus (smallpox)", section on 'Antiviral therapy'.)
Indications — We suggest antiviral therapy with tecovirimat for the following groups of patients [2] (see 'Tecovirimat' below):
●Those with severe disease (eg, hemorrhagic disease, confluent lesions, encephalitis, or other conditions requiring hospitalization).
●Those at risk for severe disease (eg, those younger than eight years of age; people with a history or presence of atopic dermatitis; persons with other active exfoliative skin conditions; persons who are pregnant or breastfeeding; persons with complications such as secondary bacterial infection, dehydration, or bronchopneumonia; immunocompromised patients) [2].
Immunocompromised patients, per the CDC, typically include those with advanced HIV-1 infection (eg, CD4 count <200 cells/microL), leukemia, lymphoma, generalized malignancy, solid organ transplantation, therapy with alkylating agents, antimetabolites, radiation, tumor necrosis factor inhibitors, high-dose corticosteroids, being a recipient with hematopoietic stem cell transplant <24 months post-transplant or ≥24 months but with graft-versus-host disease or disease relapse, or having an autoimmune disease with immunodeficiency as a clinical component [2].
●Patients with mpox infection in sites (eg, mouth, pharynx, anogenital area) that are usually associated with severe pain or might result in sequelae such as scarring or strictures.
●Patients with infection of the eye or eye accessories (eg, lids). For such patients, off-label use of trifluridine (or vidarabine) eye drops or ointments can be used in addition to tecovirimat [3]. (See 'Trifluridine (and vidarabine) eye drops or ointments' below.)
Although there are no data on timing of treatment in humans, it is likely to be most effective when started early in the course. When there is a high likelihood that the patient has mpox (eg, clinical presentation consistent with mpox after a known high-risk exposure), treatment can be started before the results of testing have returned. Updated information regarding indications for treatment of mpox during an outbreak can be found on the CDC website.
If tecovirimat is not available, the decision to treat with an alternative agent such as cidofovir (or brincidofovir, if available) must be individualized as the risk of complications are greater with these agents (eg, renal failure, electrolyte abnormalities). (See "Cidofovir: An overview", section on 'Toxicity' and 'Cidofovir/brincidofovir' below.)
Tecovirimat is generally not indicated for other patients (eg, immunocompetent persons with mild disease). Due to concerns about a low barrier to developing resistance to tecovirimat [4,5] and given the lack of efficacy data, the risk of overusing tecovirimat and developing drug-resistant virus likely outweighs the potential benefit of treatment in these individuals.
Additional considerations on management of children and pregnant persons, as well as information on administration of tecovirimat, are found below. (See 'Tecovirimat' below and 'Special populations' below.)
Specific agents
Tecovirimat — Tecovirimat (also referred to as TPOXX) is a potent inhibitor of an orthopoxvirus protein required for the formation of an infectious virus particle that is essential for dissemination within an infected host [6]. In the United States, tecovirimat was approved for the treatment of smallpox in July 2018 [7]. For treatment of mpox, the drug currently needs to be used under an expanded access program through the CDC (via local health departments) or through a clinical trial. Additional information on obtaining tecovirimat in the United States can be found on the CDC website. Clinicians can contact the CDC Clinical Consultation Team by email (ecoevent482@cdc.gov)or by phone (770-488-7100) for urgent clinical situations.
The recommended dose of tecovirimat depends upon the patient's weight; as an example, for those ≥40 kg to <120 kg, the dose is 600 mg (three capsules) every 12 hours. Detailed dosing information, including dosing in children, is described in the Lexicomp drug information monograph on tecovirimat included within UpToDate.
Oral and intravenous (IV) preparations are available. The IV formulation should not be used in patients with severe renal impairment (creatinine clearance [CrCl] <30mL/min) and should be used with caution in those with moderate or mild kidney disease as well as those <2 years of age due to accumulation of an ingredient in the IV formulation (hydroxypropyl-beta-cyclodextrin) [2]. For those who do receive the IV formulation, it can be transitioned to oral therapy once the patient can take oral medications.
The duration of treatment is typically 14 days. However, immunocompromised patients may require a longer course of therapy. Management of immunocompromised persons is found below. (See 'Immunocompromised patients' below.)
In persons with mpox, tecovirimat has generally been well tolerated [8]. As part of the approval process, tecovirimat was administered to approximately 360 human volunteers in an expanded safety trial, which found an adverse effect profile similar to that of placebo [7]. The most frequently reported side effects are headache, nausea, and abdominal pain.
In persons with HIV, there may be some potential drug interactions that impact the dosing of antiretroviral therapy agents. (See 'Persons with HIV' below.)
Data on the use of tecovirimat in humans are limited. It has been used to treat immunocompetent and immunocompromised persons, including those with proctitis [8-15]. In a report that included 255 patients who received tecovirimat, the median time to subjective improvement after starting therapy was 3 days [8]. In another series of seven patients with mpox, the one patient treated with tecovirimat had a shorter duration of viral shedding and illness compared with the others (including some that received brincidofovir) [9]. A randomized trial to study its effectiveness during the current mpox outbreak is underway [16]. Prior to the 2022 outbreak of mpox, most studies evaluating tecovirimat were in animal models, and tecovirimat protected nonhuman primates from lethal monkeypox virus infections [7,17,18]
Additional information on this agent is found in a separate topic review. (See "Variola virus (smallpox)", section on 'Tecovirimat'.)
Cidofovir/brincidofovir — Cidofovir has in vitro activity against monkeypox virus and has been shown to be effective against lethal monkeypox virus challenge in animal models [19-21]. However, there are no clinical data regarding its efficacy against mpox in humans, and its use can be associated with significant adverse events, including nephrotoxicity. (See "Cidofovir: An overview".)
In June 2021, brincidofovir was approved for use in the United States for treatment of smallpox [22]; it is available through an FDA emergency investigational drug (EIND) protocol. Brincidofovir is a prodrug of cidofovir that can be given orally. (See "Variola virus (smallpox)", section on 'Brincidofovir'.)
There are only limited published data with the use of brincidofovir for treatment of mpox. Animal models show that it is likely an effective treatment of orthopoxvirus infections [23-25]. However, in one case series, three patients with mpox were treated with brincidofovir (200 mg once a week orally), and all developed elevated liver enzymes resulting in discontinuation of therapy [9].
Trifluridine (and vidarabine) eye drops or ointments — If mpox lesions involve the eye or accessory structures of the eye (eg, lids), trifluridine (or vidarabine) eye drops or ointments can be used in addition to tecovirimat. Drops or ointments should be applied every four hours for 7 to 10 days. Topical trifluridine or vidarabine has been used to treat vaccinia of the cornea and conjunctiva and to prevent corneal and conjunctival involvement in patients with eyelid lesions [3].
Additional considerations
Immunocompromised patients — Immunocompromised patients are at risk for developing severe disease. Thus, in addition to using tecovirimat, efforts should be made to improve their immune function (eg, limiting the use of immunosuppressive medications, initiating antiretroviral therapy for those with HIV). (See 'Tecovirimat' above and 'Persons with HIV' below.)
Some patients with severe immunocompromise may continue to develop lesions after a 14-day course of tecovirimat. In this setting, clinicians may consider sending a repeat swab for sequencing to determine if there is evidence of viral resistance. For those with no evidence of resistance, it is reasonable to continue tecovirimat (with emphasis for the need for a fatty meal for optimal absorption) until there is clinical improvement (but not beyond 90 days); by contrast, if there is evidence for viral resistance, a second anti-viral agent like cidofovir (or brincidofovir if it becomes available) can be added [26]. Such patients should be managed in consultation with an infectious disease specialist or public health official (eg, the CDC mpox consultation team in the United States).
If PCR testing is negative for orthopoxvirus, other causes of ongoing lesions should be suspected, such as bacterial superinfection. (See 'Management of complications' below.)
Management of complications — Secondary bacterial infections can occur in patients with mpox. Patients should be counseled to contact their health care provider if they observe increased erythema, warmth, or purulence surrounding any lesions, which could suggest secondary bacterial skin infection. Should a bacterial infection be suspected at the time of the initial evaluation or during follow-up visits, the patient should receive appropriate antibiotic coverage in addition to antiviral therapy; regimens should generally include agents that are used to treat soft tissue infections (eg, those that cover both staphylococcal and streptococcal species). (See "Acute cellulitis and erysipelas in adults: Treatment".)
Management of other complications may include treatment of balanitis or balanoposthitis causing urethral meatal obstruction as well as management of ocular infection. (See "Balanitis in adults", section on 'Management' and 'Trifluridine (and vidarabine) eye drops or ointments' above.)
Management of ocular infections — Mpox involvement of the eye (eg, conjunctivitis, blepharitis, keratitis, corneal ulceration) is rare, but when present requires urgent treatment since corneal scarring and vision loss are potential complications. Treatment should include systemic therapy with tecovirimat; in addition, for those with keratitis, trifluridine should also be considered [27]. In a case series of five patients who received antiviral therapy (tecovirimat and/or trifluridine), all but one had improvement, and that patient may have had trouble adhering to his initial treatment regimen [28]. Such patients should be managed in consultation with an ophthalmologist.
INFECTION PREVENTION AND CONTROL — The risk of transmitting monkeypox virus to others in community and health care settings can be mitigated through implementation of infection prevention and control measures. Our approach to infection prevention and control is summarized below. Additional recommendations for the home and health setting can be found on the United States Centers for Disease Control and Prevention (CDC) website [29].
The identify, isolate, inform framework is critical to reducing the risk of transmission in health care settings and has been applied broadly to high-consequence infectious diseases (HCIDs), including Ebola virus disease [30,31] and Middle East respiratory syndrome [32] as well as non-HCIDs, such as measles [33]. The identify component seeks to ensure that clinicians have the information they need to consider a particular diagnosis at the earliest interactions with the health care system. This requires knowledge of clinical signs and symptoms as well as relevant epidemiology, which may include travel and specific exposures.
Once identified, clinicians need to ensure the patient with the suspected infection of interest is appropriately isolated. Once isolated, the next step is to inform, which requires that the clinicians contact the appropriate individual within their facility for additional guidance. This is often the infection prevention and control team, who serve as liaisons with public health authorities as required.
Health care settings — In the health care setting, use of standard precautions are applied to all patients, including individuals being considered for mpox [34]. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Standard precautions'.)
Although reports of nosocomial transmission are few, and have primarily been associated with high-risk exposures from sharps injuries [35-39], we suggest the following approach to infection control in the healthcare setting. These recommendations are based on guidance from the CDC and World Health Organization (WHO) [40,41], as well as experience in our own institutions.
●Patient placement (room selection) – A patient with suspected or confirmed mpox should be triaged promptly to a single-person (private) room with dedicated toileting facilities. If a patient is in a semi-private room at the time that mpox is suspected, the patient with suspected mpox should be moved to a private room as soon as possible. Pending that transfer, both patients should be masked, the curtain between the beds should be closed, and each patient should be provided with a commode to use. Patients should not share the bathroom. If the patient is eventually diagnosed with mpox, any patients who shared the room should be evaluated to determine the exposure risk. (See 'Post-exposure management' below.)
Special air handling is generally not required. However, an airborne infection isolation room (AIIR; "negative pressure") should be used for any procedures that are likely to aerosolize oral secretions. An AIIR should also be used pending the initial diagnostic work-up when diseases that require an AIIR, such as varicella (chickenpox), are being considered (see "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)", section on 'Differential diagnosis'). If an AIIR is not available in these circumstances, the patient should be placed in a private, standard room with the door closed when it is safe to do so. Patients should don a facemask when any individual enters the room or when the patient needs to travel outside the room.
●Personal protective equipment – Personal protection equipment (PPE) is required for all health care personnel (HCP) interacting with a patient with suspected or confirmed mpox or interacting with the patient's environment (eg, environmental services HCP).
All HCP should use a gown, gloves, eye protection (goggles or face shield), and a National Institute for Occupational Safety and Health (NIOSH)-approved N95 filtering facepiece or equivalent or higher-level respirator. This combination of PPE reflects contact precautions (gown and gloves), droplet precautions (eye protection), and airborne precautions (respiratory protection). While there is no epidemiologic evidence to date that monkeypox virus is spread by the airborne route, at this time the CDC recommends respiratory protection be used [41].
Careful attention must be paid to doffing (removal) of PPE in the correct order and in a manner that reduces the risk of self- and cross-contamination. Hand hygiene must immediately follow doffing of PPE.
All HCP determined to have had an exposure to mpox should be monitored for symptoms for 21 days from the day of last interaction (table 1). The approach to monitoring (active or passive) and the need for post-exposure prophylaxis (PEP) depend upon the type of exposure, use of PPE, and local regulations. This is discussed in detail elsewhere. (See 'Post-exposure management' below.)
●Patient transport – Patient transport outside the room should be limited to those essential for the care of the patient and for procedures or interventions that cannot be performed in the patient room [42]. If transport is necessary, the patient should wear a medical mask during transport and any exposed skin lesions should be covered with a clean sheet or gown. During transport, there must be an HCP with clean, nongloved hands who is able to open doors and push elevator buttons as needed. The receiving department should be notified in advance of the required precautions.
●Care of the environment – Standard cleaning and disinfection procedures should be performed using an Environmental Protection Agency (EPA)-registered hospital-grade disinfectant with an emerging viral pathogen claim.
When handing soiled laundry (eg, bedding, towels, personal clothing), contact with lesion material that may be present on the laundry should be avoided. In addition, soiled laundry should be gently and promptly contained in an appropriate laundry bag and should never be shaken or handled in a manner that may disperse infectious material.
Activities such as dry dusting, sweeping, or vacuuming should be avoided. Wet cleaning methods are preferred to avoid mobilizing viral particles.
●Waste management – During the 2022 outbreak, our approach to waste management in health care facilities is conducted in accordance with the US Department of Transportation (DOT) Hazardous Materials Regulations (HMR; 49 CFR, Parts 171-180).
If the patient is suspected or confirmed to be infected with the West African clade of monkeypox virus (clade 2), waste (ie, bodily fluids such as urine, stool, blood, sharps, used PPE, and other waste generated in the course of care) is managed as routine hospital medical waste. By contrast, waste generated from a patient suspected or confirmed to be infected with the Central African clade (clade 1) is considered Category A waste and additional precautions should be taken [43].
In nonendemic countries, it is reasonable to assume that patients with suspected or confirmed mpox during the 2022 outbreak have infection with the West African clade (clade 2). However, individual facilities should review this approach with their local and state public health officials as local considerations may apply (eg, if there are epidemiologic data that could implicate infection with the Central African clade [clade 1] of monkeypox virus) [41].
Community settings — Most patients with mpox will have mild disease and can be cared for at home. Such patients should not leave home except for follow-up medical care; when leaving home, public transportation should be avoided. Unexposed persons who do not have an essential need to be in the home should not visit while the individual remains infectious. (See 'When to discontinue isolation' below.)
Patients with monkeypox virus should be isolated in a room or area separate from other family members and pets. This is particularly important for persons with extensive lesions that cannot be easily covered and those with respiratory symptoms.
If around others:
●Skin lesions should be covered (eg, long sleeves, long pants) to minimize risk of contact with mpox lesions [44].
●Patients should avoid sharing their used clothes, towels, food, utensils, or face masks with others and should not allow animals to access them.
●Individuals with mpox should wear a well-fitting facemask when around others, even if respiratory symptoms are not present. Ideally, household members should wear a facemask when in the presence of the person with mpox as well.
Household members providing care to patients with mpox should use disposable gloves for direct contact with lesions. The gloves should be disposed of after use, followed by hand hygiene with an alcohol-based hand rub or, if visibly soiled, with soap and water. Disposal of contaminated waste (such as dressings and bandages) should be determined in consultation with state or local health officials.
Hand hygiene should also be performed regularly by infected individuals and by household contacts after any unprotected contact with lesions or potentially contaminated surfaces.
Similar to health care settings, as described above, care should be used when handling soiled laundry to avoid direct contact with contaminated material. Soiled laundry should not be shaken or otherwise handled in a manner that may disperse infectious particles. Laundry may be washed in a standard washing machine with water and detergent.
Additional information on isolation and prevention in the community setting can be found on the CDC website.
When to discontinue isolation — Persons with mpox should be considered infectious until all lesion scabs have fallen off and re-epithelialization has occurred, which typically lasts two to four weeks [44]. Decisions regarding discontinuation of isolation precautions in both the health care facility and the community should be made in consultation with the local or state health department.
Precautions after recovery — The WHO suggests consistent condom use during any sexual activity for 12 weeks after recovery [40]. Monkeypox virus can be found in semen and vaginal fluids, and the role of sexual transmission of monkeypox virus is still being evaluated. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)", section on 'Routes of person-to-person transmission'.)
POST-EXPOSURE MANAGEMENT — All individuals with an exposure to mpox should monitor for symptoms. The need for post-exposure prophylaxis (PEP) with vaccine depends upon the risk of the exposure (table 1). (See 'Monitoring after an exposure' below and 'Post-exposure prophylaxis' below.)
Exposure definition and risk stratification — Exposures in both community and health care settings should be assessed to determine the risk of monkeypox virus transmission. The United States Centers for Disease Control and Prevention (CDC) defines exposures as higher, intermediate, or lower risk, as described in the table (table 1) [45]. The exposure risk depends upon the type of exposure (eg, if the exposed person had nonintact versus intact skin), the setting (community versus health care), and if appropriate personal protection equipment (PPE) was used.
However, exposures may be recategorized to a particular risk level at the discretion of public health authorities. In the United States, updated information can be found on the CDC website. In addition, other public health agencies, such as the World Health Organization (WHO) and the United Kingdom Health Security Agency (UKHSA), may have different risk stratification schemes, which may differ on risk classification, recommendations for PEP, and movement restrictions during the observation period [46,47].
Individual institutions should coordinate their response to an exposure with their local and state public health authorities. In health care facilities, occupational health and infection prevention and control experts routinely manage contact tracing and exposure notification and management and are responsible for such activities related to mpox. In community settings, these efforts are coordinated through local and state public health officials with involvement of local health care facilities as necessary.
Monitoring after an exposure — All individuals, regardless of level of exposure risk, should monitor for symptoms for 21 days after their last exposure (table 1) [48]. Symptom monitoring can be active (eg, occupational health or public health worker checks in directly with an exposed individual on a daily basis) or passive (eg, exposed individual self-monitors and reports symptoms to a preidentified contact in the occupational health or public health department).
Contacts who remain asymptomatic can continue routine daily activities. However, if symptoms develop, they should immediately self-isolate and contact the health department for further guidance or, in the case of HCP, their local occupational health or infection prevention and control contact. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)", section on 'Clinical manifestations'.)
While there are no specific restrictions on activities during the exposure period, the United States CDC recommends that exposed individuals refrain from donating blood, cells, tissue, breast milk, semen, or organs during the 21-day period [48].
Post-exposure prophylaxis — Certain patients should be offered post-exposure vaccination with one of the available orthopoxvirus vaccines. (See 'Indications after a known exposure' below and 'Orthopoxvirus vaccines' below.)
Although the efficacy of PEP during the 2022 outbreak has not yet been established, during the 2003 United States outbreak, it appears to have reduced the risk of developing mpox. In published reports from the 2003 outbreak, 28 adults and two children received the replication-competent smallpox vaccine for this purpose, and no cases of mpox were identified among these recipients [34,49,50]. However, it is not known how many individuals were exposed and not given PEP.
Efforts should be made to ensure an equitable approach to vaccination so that all persons at risk for mpox have access to the vaccine, regardless of race or ethnicity [51]. Community engagement programs, including those that focus on racial and ethnic minorities, can help reduce health disparities [52,53].
Orthopoxvirus vaccines
Types of vaccines — There are two available vaccines that can reduce the risk of developing mpox. The modified vaccinia Ankara (MVA) vaccine (JYNNEOS in the United States, IMVANEX in the European Union, and IMVAMUNE in Canada) and ACAM2000 vaccine.
●MVA vaccine – The MVA vaccine is made from a highly attenuated, nonreplicating vaccinia virus and has an excellent safety profile, even in immunocompromised people and those with skin disorders. The MVA vaccine is administered as two doses four weeks apart. In the United States, JYNNEOS is approved for the prevention of smallpox and mpox.
●ACAM2000 – ACAM2000 is a replication-competent smallpox vaccine that can only be used in select patients and is associated with more adverse events than the MVA vaccine. In the United States, ACAM2000 is approved for the prevention of smallpox. It can be used for the prevention of mpox under an expanded-access investigational new drug (IND) application through the CDC.
Detailed information on these vaccines, including dosing recommendations, can be found on the CDC website and in a separate topic review. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses".)
Indications after a known exposure — The indications for PEP are typically dictated by public health authorities and depend upon the exposure risk, as described above (table 1). (See 'Exposure definition and risk stratification' above.)
Our approach, which is consistent with guidelines from the CDC, is as follows [48]:
●Higher risk exposure – For most individuals who have had a high-risk exposure to mpox, we suggest post-exposure vaccination with the MVA vaccine (table 1). However, vaccination is not needed for those who already developed mpox since recent mpox likely confers immune protection [54]. (See 'Exposure definition and risk stratification' above.)
If the MVA vaccine is not available, ACAM2000 may be considered in select immunocompetent patients on a case-by-case basis. However, this vaccine is associated with more side effects and contraindications than the MVA vaccine, and most clinicians would avoid using ACAM2000 to prevent mpox during the current outbreak since the risks associated with vaccination may be greater than those associated with infection with the circulating strain of monkeypox virus. If ACAM2000 is being considered in the United States, it requires approval through an expanded-access program by the CDC. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses", section on 'Complications' and "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)", section on 'Prognosis and risk for severe disease'.)
●Intermediate risk exposure – For individuals with intermediate-risk exposures (table 1), the need for PEP should be determined on a case-by-case basis evaluating the likelihood of transmission from the specific exposure versus the risk of post-exposure vaccination. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses".)
●Lower risk exposure – Post-exposure vaccination is not indicated for those with a lower-risk exposure.
The risks and benefits of vaccination in persons who are pregnant or breastfeeding are outlined below. (See 'Pregnancy' below.)
Persons who are eligible for PEP should be vaccinated within four days of exposure whenever possible, although vaccination can be considered for up to 14 days of an exposure. Recommendations for vaccination from different public health agencies (eg, CDC, WHO, UKHSA) may vary [46,47]. (See 'Exposure definition and risk stratification' above.)
Peak immunity is expected approximately 14 days after the second dose of vaccine. Thus, it is important that persons who are vaccinated continue to monitor for signs and symptoms of mpox even after vaccination. (See 'Monitoring after an exposure' above.)
Data emerging from the 2022 outbreak support the efficacy of post-exposure vaccination in reducing the risk of mpox after an exposure. In a report that evaluated 6,471 mpox cases in the United States, 85 percent occurred in those who were unvaccinated [55]. Among those who develop mpox after vaccination, most cases have occurred soon after the first dose of the vaccine was administered [55-57]. In a study that followed 7339 individuals who received the MVA vaccine, mpox developed in 90 patients, with the majority developing during the first 14 days after receiving the first dose of vaccine (37 cases during days 1 to 7, 32 during days 8 to 14) [57]. Eight cases occurred more than 28 days after receiving their first dose of vaccine, including two which developed more than 14 days after the second dose; however, all but one of these cases were mild.
Indications for those with a suspected exposure — During the mpox outbreak that began in 2022, the CDC has expanded the indications for vaccination to include people who are likely to have been exposed to mpox (referred to as expanded PEP or PEP++) (table 1) [58-60]. This includes certain gay, bisexual, or other men who have sex with men, or transgender and gender-diverse people who have sex with men, who report any of the following in the last 14 days: having sex with multiple partners; having sex at a commercial sex venue; or having sex in association with an event, venue, or defined geographic area where transmission of monkeypox virus is occurring [60].
The goal of expanded PEP is to help slow the spread of the current outbreak by providing vaccination to people in the community who are most likely to have a recent exposure to mpox. However, because supplies of JYNNEOS are limited [61], this strategy is only being rolled out in certain jurisdictions. There may be additional indications for vaccination as supplies of vaccine become more available.
It is important that persons who are vaccinated continue to monitor for signs and symptoms of mpox and reduce their risk of exposure since the efficacy of vaccination during this outbreak has not been established. (See 'Monitoring after an exposure' above and 'Reducing risk of exposure' below and 'Infection prevention and control' above.)
The indications for pre-exposure prophylaxis (PrEP) are discussed below. (See 'Pre-exposure prophylaxis with orthopoxvirus vaccines' below.)
Vaccinia immune globulin — The use of intravenous (IV) vaccinia immune globulin (VIG) may be considered in immunocompromised patients with an exposure history. Immunization with replication-competent vaccinia virus vaccine is contraindicated [62], and those receiving MVA vaccine may not respond appropriately. In the United States, this agent is available through the CDC. Clinicians can contact the CDC Clinical Consultation Team by email (ecoevent482@cdc.gov) or by phone for urgent clinical situations (770-488-7100).
Other options — Although vaccination with one of the orthopoxvirus vaccines is the preferred method for PEP, there are times when the MVA vaccine and/or VIG are not available or are contraindicated. In these settings, antiviral therapy with tecovirimat may be reasonable. However, there are no data with this approach, so the decision to treat must be determined on a case-by-case basis after assessing the exposure risk and the risk for developing severe disease.
PRE-EXPOSURE PROPHYLAXIS WITH ORTHOPOXVIRUS VACCINES — Certain individuals are at increased risk for orthopoxvirus infection due to behavioral or occupational factors and should be offered pre-exposure prophylaxis (PrEP) with the live, nonreplicating, modified vaccinia Ankara (MVA) vaccine. Although a replication-competent smallpox vaccine (ACAM2000) may be considered when the MVA vaccine is not available, it can only be used in select persons because of an increased risk of side effects/adverse reactions. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses" and 'Types of vaccines' above.)
Patients who received pre-exposure prophylaxis should still be monitored after an exposure; however, additional post-exposure vaccination is not indicated. (See 'Post-exposure management' above.)
Persons with behavioral risk — In the United States, the CDC recommends that PrEP for mpox be offered to the following groups with behavioral risk factors for exposure to mpox [60]:
●Gay, bisexual, and other men who have sex with men, transgender, or nonbinary people who in the past six months have had:
•A new diagnosis of one or more nationally reportable sexually transmitted diseases (ie, acute HIV, chancroid, chlamydia, gonorrhea, or syphilis)
•More than one sex partner
●People who have had any of the following in the past six months:
•Sex at a commercial sex venue
•Sex in association with a large public event in a geographic area where monkeypox virus transmission is occurring
●Sexual partners of people with the above risks
●People who anticipate experiencing the above risks
In addition, we discuss pre-exposure vaccination with staff at establishments where sexual activity occurs (eg, bathhouses, saunas, sex clubs) and with sex workers (regardless of venue).
Vaccination can also be considered on a case by case basis for those self-attesting to being eligible for PrEP without specifying a clear indication as long as it is determined that the potential risks and benefits of vaccination are fully understood [60]. Some patients who engage in high-risk behaviors may not be comfortable disclosing their sexual risk, and this can help decrease the stigma of vaccinating against mpox and increase equitable delivery of the vaccine.
Persons with occupational risk — In 2021, the Advisory Committee on Immunization Practices (ACIP) voted to recommend the use of the MVA vaccine for certain workers at high risk for occupational exposure to orthopoxvirus infection, such as research laboratory personnel and specialized clinical laboratory personnel performing diagnostic testing for orthopoxviruses (eg, labs that are part of the Laboratory Response Network) as well as designated response team members who are at risk for occupational exposure to orthopoxviruses, in consultation with local public health authorities. The ACIP also recommended offering vaccination to those who administer ACAM2000 (or care for patients infected with replication-competent orthopoxviruses, based on shared clinical decision-making) [63]. In 2022, the United States Centers for Disease Control and Prevention (CDC) approved the updated ACIP smallpox vaccine recommendations related to pre-exposure prophylaxis (PrEP), including the use of booster vaccination as immunity can wane [64].
Rationale — The benefit of smallpox vaccination in preventing mpox was demonstrated in a study of human-to-human transmission of monkeypox virus in Africa [34]. Secondary attack rates varied greatly among 2278 household contacts depending on their prior smallpox vaccination status (7.5 compared with 1.3 percent in vaccinated and unvaccinated subjects). In another study that showed an increasing incidence of human mpox cases in Africa [65], vaccinated people had a fivefold lower risk of mpox as compared with unvaccinated persons (0.78 versus 4.05 per 10,000); vaccine efficacy was estimated to be approximately 81 percent in those with a distant history of smallpox vaccination.
In the 2003 United States outbreak, an investigation using experimental techniques identified three asymptomatic mpox infections in individuals who had received smallpox vaccination 13, 29, and 48 years prior to their exposure to mpox [66]. These individuals were unaware that they had been infected because they did not have any recognizable disease symptoms, and no transmission was documented. These findings suggested that past vaccination prevented symptomatic mpox disease. However, symptomatic mpox infections have been seen in people who had smallpox vaccination in the distant past [67-69].
REDUCING RISK OF EXPOSURE — Persons in communities where there has been substantial transmission of monkeypox virus should try to reduce the risk of new exposures. Although pre- and post-exposure prophylaxis likely reduces the risk of developing infection, the efficacy of vaccination during an outbreak has not been established. (See 'Post-exposure prophylaxis' above.)
In the 2022 outbreak, most cases of mpox have been identified in men who have sex with men who reported high-risk sexual behaviors (eg, sex with multiple partners) as a potential risk factor [70]. Information on strategies to reduce sexual risk can be found on the website.
More detailed information on transmission of monkeypox virus and the use of infection prevention strategies to reduce exposure are discussed elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)", section on '2022 global outbreak' and "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)", section on 'Human-to-human transmission' and 'Infection prevention and control' above.)
SPECIAL POPULATIONS
Pregnancy — Pregnant persons who are diagnosed with mpox or have had an exposure to mpox should be managed in consultation with a maternal-fetal specialist, if possible.
●Management of persons with mpox
•Antiviral therapy – The United States Centers for Disease Control and Prevention (CDC) guidance suggests antiviral treatment with tecovirimat for pregnant and breastfeeding persons infected with monkeypox virus. This approach is based on concerns for an increased risk of severe disease during pregnancy, the risk of transmitting monkeypox virus to the fetus during pregnancy or to the newborn during and after birth, and the risk of severe infection in the newborn, if infected [71]. Information on the risks of tecovirimat to the fetus are limited to animal studies. In those studies, animals received oral tecovirimat at levels approximately 23 times higher than recommended human doses, and no specific fetal adverse effects were observed. (See 'Antiviral therapy' above.)
•Fetal surveillance – Given the potential for serious in utero infection, fetal surveillance with nonstress tests and/or biophysical profiles is reasonable during acute maternal infection if delivery would be performed for nonreassuring fetal status [72]. Fetal ultrasound examination at monthly intervals until delivery has been suggested as a prudent approach since so little is known about the natural history of mpox in pregnancy.
•Considerations for delivery – Timing of delivery is based on standard medical and obstetric indications [73]; however, the optimum route of delivery is unclear. Cesarean birth has been recommended for patients with genital lesions to reduce the risk of intrapartum transmission; however, the benefit is unknown since antepartum transmission may have occurred.
•Reducing transmission risk – Uninfected newborns born to infected mothers should be isolated from other newborns [74]. The infected parent should additionally be restricted from interactions with their uninfected newborn until they are determined to no longer be infectious, given the risk of severe illness were the newborn to develop mpox. Exceptions to restricting interactions between mother and newborn, if considered, should involve input from local infection prevention and control specialists to assess the risks of transmission.
Those with active mpox should not breastfeed an uninfected newborn if an acceptable alternative is available; however, it is not certain whether monkeypox virus can be transmitted through the breastmilk of an infected parent versus the close contact associated with direct feeding at the breast.
●Management after an exposure to mpox – Persons who are pregnant should be offered post-exposure vaccination with the modified vaccinia Ankara (MVA) vaccine if indicated, as described above. (See 'Post-exposure prophylaxis' above.)
The risks and benefits of vaccination in persons who are pregnant or breastfeeding are outlined on the CDC website. Key consideration used in shared decision-making should include:
•Risk level of exposure. (See 'Exposure definition and risk stratification' above.)
•Risk of mpox for the pregnant person. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)", section on 'Prognosis and risk for severe disease'.)
•Risk of mpox for the fetus. Data on pregnancy outcomes in persons with mpox are very limited. However, available data prior to the 2022 outbreak of mpox suggest mpox during pregnancy is associated with a high risk of perinatal loss and vertical transmission [75].
The largest series evaluating fetal outcomes included four pregnant patients with mpox infection in the Democratic Republic of Congo, two with moderate/severe disease had spontaneous first trimester pregnancy losses (pregnancy tissue was not tested for infection) [76]. One patient with moderate disease at 18 weeks had a fetal demise at 21 weeks with virological, histological, serological, and clinical evidence of in utero monkeypox virus infection, including diffuse cutaneous maculopapillary lesions on the fetal head, trunk, and extremities; marked hepatomegaly with peritoneal effusion; and hydrops fetalis. The fourth patient had mild disease at 14 weeks and gave birth to a healthy newborn at term. In another report of a probable (nonlaboratory confirmed) case of mpox in a pregnant patient infected at about 24 weeks of gestation, preterm birth occurred at about 30 weeks, and the newborn had a generalized skin rash consistent with mpox and died of malnutrition a few weeks later [77].
•Risk of vaccination. There are currently no US Food and Drug Administration (FDA)-approved smallpox vaccines for pregnancy. Animal studies of the MVA vaccine in pregnant rats have not demonstrated adverse fetal effects. In addition, available human data from European and United States registries of inadvertently vaccinated pregnant persons (eg, during studies and vaccination campaigns) are reassuring and do not demonstrate increased risk of miscarriage, birth defects, preterm birth, or fetal vaccinia [78,79].
Similar to other live attenuated virus vaccines, the MVA vaccine is considered safe during breastfeeding; therefore, any post-partum patient with a significant exposure should be offered vaccination to prevent mpox for the patient and the newborn.
Children and adolescents — Data on children with mpox are limited. Although there is evidence that the disease is more likely to be severe in children younger than eight years infected with the Congo Basin clade (clade 1) of monkeypox virus, there is less experience with the West African clade (clade 2). (See "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)", section on 'Virology'.)
●Treatment –In children with mpox, treatment with tecovirimat is warranted for those with severe disease (airway obstruction, confluent lesions, encephalitis), those with complications (cellulitis/abscess, ocular lesions, pneumonia, or sepsis), and those with lesions involving anatomic areas that might result in serious sequelae, such as scarring or strictures (eg, infections involving the eyes, face, or genitals) [80]. Antiviral therapy should also be considered for those felt to be at increased risk for severe disease (eg, children <8 years of age, children with eczema and other skin conditions, and immunocompromised children).
The decision to use alternative agents, such as vaccinia immune globulin or cidofovir, must be determined on a case-by-case basis. More detailed information on antiviral agents is found above. (See 'Specific agents' above.)
Experience using antiviral therapy for the treatment of children with mpox is limited. In one case report that described the management of a severely ill two-week old who had mpox and adenovirus infection, the infant improved after receiving tecovirimat (50 mg twice daily) and IV cidofovir [81].
●Prevention – Post-exposure vaccination with the MVA vaccine should be considered for those >6 months of age after a high-risk exposure [74]. Although the MVA vaccine is not approved for those younger than 18, there are no known contraindications.
If the MVA vaccine is not available, the decision to use the replication-competent smallpox vaccine (ACAM2000) in healthy children older than 12 months must be individualized, as it is associated with more severe adverse reactions and complications. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses", section on 'Complications'.)
For infants <6 months, post-exposure vaccination may not be effective, and other prophylactic measures (eg, vaccinia immune globulin [VIG], antiviral therapy) can be considered on a case-by-case basis.
Additional information on mpox in children and adolescents can be found on the CDC website.
Persons with HIV — During the global mpox outbreak that started in May 2022, 30 to 50 percent of patients have had concomitant HIV [82-84]. It is not known if HIV infection increases a person's risk of acquiring mpox after exposure. However, people with advanced HIV may be at increased risk of severe disease related to monkeypox virus infection [26].
For persons with HIV who have mpox, anti-monkeypox virus therapy should be considered for those who are immunocompromised and at risk for severe disease (eg, CD4 count <350 cells/microL). In addition, ART should be continued [85]. For persons with newly diagnosed HIV and those who are not taking ART, ART should be started as soon as possible. Discussions of ART regimen selection are presented separately. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach" and "Switching antiretroviral therapy for adults with HIV-1 and a suppressed viral load".)
There are potential drug interactions with tecovirimat and certain ART agents (eg, doravirine, rilpivirine, maraviroc). Although dose adjustments of these agents were initially considered for persons receiving tecovirimat, more recent guidelines state these adjustments are not required [86,87]. However, cabotegravir-rilpivirine should not be initiated during tecovirimat therapy or for two weeks after tecovirimat has been completed [87]. (See "Use of long-acting cabotegravir-rilpivirine in people with HIV".)
Post-exposure prophylaxis (PEP) with the MVA vaccine should be administered to those who warrant prophylaxis (see 'Post-exposure management' above). Patients with CD4 counts >350 cells/microL had antibody responses after MVA vaccination similar to non-HIV-infected patients [88]. In another study that included HIV-infected patients with CD4 counts between 200 and 350 cells/microL, antibody responses were present but lower than non-HIV-infected patients [89].
The ACAM2000 vaccine is generally contraindicated in persons with uncontrolled HIV since it is a live, replication-competent vaccine, and the risks generally outweigh the benefits in the setting of the current mpox outbreak [90]. However, while it has not been widely used during the current outbreak, if only ACAM2000 is available for PEP, it can be considered on a case-by-case basis for those with a CD4 count of >500 copies/microL and no other contraindications.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Mpox (monkeypox) (The Basics)")
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Orthopoxvirus (smallpox and monkeypox)".)
SUMMARY AND RECOMMENDATIONS
●Causative agent – Monkeypox virus, the causative agent of mpox (previously referred to as monkeypox) is an orthopoxvirus in the same genus as variola virus (the causative agent of smallpox) and vaccinia virus(the virus used in smallpox vaccine). (See 'Terminology' above.)
Patients with mpox typically develop a distinctive rash, but it can also be similar in appearance to some other viral infections (eg, herpes simplex infection, varicella-zoster virus infection).
Most cases of mpox prior to 2022 have occurred in Central and West Africa. However, an ongoing outbreak associated with person-to-person transmission was reported in May 2022 and has involved thousands of individuals in nonendemic countries. Details of this outbreak are presented elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)".)
●Patient management – Most patients with mpox have mild disease and recover with supportive care. (See 'Supportive care' above.)
However, we suggest antiviral therapy with tecovirimat for individuals with or at risk for severe disease and those with lesions in the eyes, mouth, or anogenital area (Grade 2C). Although there is limited experience using this agent, tecovirimat appears to be well tolerated and may shorten the duration of illness and viral shedding. (See 'Antiviral therapy' above and 'Special populations' above.)
The decision to use an alternative agent (eg, cidofovir/brincidofovir) must be individualized given the increased risk of adverse events.
●Infection prevention and control – If the diagnosis of mpox is being considered, infection prevention precautions should be implemented to reduce the risk of transmission. (See 'Infection prevention and control' above.)
All health care personnel (HCP) involved in the care of a patient with mpox should use a gown, gloves, eye protection (goggles or face shield), and a National Institute for Occupational Safety and Health (NIOSH)-approved N95 filtering facepiece or equivalent or higher-level respirator. (See 'Health care settings' above.)
Special air handling is generally not required; however, an airborne infection isolation room (AIIR) should be used if the diagnosis is unclear (eg, those with suspected varicella) and/or if procedures that are likely to spread oral secretions (eg, intubation) are anticipated to be performed.
●Post-exposure management
•Monitoring – All individuals with confirmed exposures to mpox (table 1) should monitor for symptoms for 21 days. Contacts who remain asymptomatic can continue routine daily activities. If symptoms develop, they should immediately self-isolate and contact the health department or other designated point of contact (eg, occupational health for HCP) for further guidance. (See 'Monitoring after an exposure' above.)
•Vaccination – Decisions regarding post-exposure vaccination depend primarily upon the type of exposure. The United States Centers for Disease Control and Prevention (CDC) defines exposure risk as higher, intermediate, or lower (table 1). (See 'Exposure definition and risk stratification' above.)
-Known higher-risk exposure – For those with a known higher-risk exposure, we suggest post-exposure prophylaxis (PEP) with the modified vaccinia Ankara (MVA) vaccine in addition to monitoring (Grade 2C). The MVA vaccine is made from a highly attenuated, nonreplicating vaccinia virus and has an excellent safety profile, even in immunocompromised people and those with skin disorders. (See 'Indications after a known exposure' above.)
The use of the replication-competent vaccine (ACAM2000) may be reasonable for select immunocompetent patients when the MVA vaccine is not available. In the United States, its use for prevention of mpox would need to be done under an expanded-access program through the CDC.
-Suspected higher-risk exposure – Where MVA vaccine is available, it may be offered to individuals who do not have a confirmed exposure but are at high risk for recent exposure (eg, based on sexual risk). This is referred to as expanded PEP or PEP++. (See 'Indications for those with a suspected exposure' above.)
-Other exposures – PEP should be considered for individuals after specific intermediate-risk exposures on a case-by-case basis. By contrast, vaccination is not indicated for those with lower-risk exposures. (See 'Indications after a known exposure' above.)
●Pre-exposure prophylaxis – The MVA vaccine should be offered as pre-exposure prophylaxis (PrEP) to selected persons at risk for orthopoxvirus infection due to behavioral or occupational risk factors. (See 'Pre-exposure prophylaxis with orthopoxvirus vaccines' above.)
●Special populations – There are certain considerations for treatment and prevention of mpox in children and adolescents, persons with HIV, and those who are pregnant, as discussed above. (See 'Pregnancy' above and 'Children and adolescents' above and 'Persons with HIV' above.)
