Treatment and prevention of mpox (formerly monkeypox)

INTRODUCTION — 

Monkeypox virus (MPXV) 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 and mpox 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 virus infection, and varicella-zoster virus infection.

Prior to 2022, most cases of mpox occurred in Central and West Africa. However, a global multi-country outbreak associated with person-to-person transmission, which was first recognized in May 2022, has involved tens of thousands of individuals in over 100 previously 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 (formerly monkeypox)".)

TERMINOLOGY — 

In November 2022, the World Health Organization (WHO), which 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 is still officially named monkeypox virus until the International Committee on the Taxonomy of Viruses (ICTV) decides if a name change is needed. However, the former Congo Basin (Central African) clade was renamed as Clade one (1) and the former West African clade was renamed as Clade two (2). Infection with Clade 1 is typically associated with more severe disease. A more detailed discussion of these different clades is presented in a separate topic review. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Virology'.)

CLINICAL MANAGEMENT — 

Management of patients with mpox involves supportive care as well as antiviral therapy for select patients. Additional considerations for managing pregnant persons, children, and individuals with immunocompromising conditions, such as advanced human immunodeficiency viruses (HIV), are discussed below. (See 'Special populations' below.)

Supportive care — Most immunocompetent 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.

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. However, data supporting their efficacy for patients with mpox are limited, and in the United States, none of the available agents are Food and Drug Administration (FDA)-approved for this indication. During the outbreak that began in 2022, tecovirimat was the agent most commonly used since it was available through an expanded access investigational new drug (EA-IND) protocol held by the CDC and was well tolerated, but subsequent clinical trials of tecovirimat in humans have not provided clear evidence of efficacy in persons eligible for randomization [2,3]. (See 'Tecovirimat' below.)

Indications — We suggest antiviral therapy for the following groups of patients with confirmed mpox or with suspected mpox pending confirmation, as described in the table (table 1) and summarized below [4,5]:

●Patients who are severely immunocompromised

●Patients with active skin conditions placing them at higher risk for disseminated infection

●Persons who are pregnant or lactating, regardless of illness severity or underlying comorbidities at presentation

●Persons <18 years of age, regardless of illness severity or underlying comorbidities at presentation

●Patients with protracted or life-threatening manifestations of mpox, including ocular disease

In the United States, these patient groups meet the criteria to receive tecovirimat through the EA-IND protocol, which is available through the CDC. These criteria were published in June 2024. Updated information regarding indications for tecovirimat can be found on the CDC website. (See 'Tecovirimat' below.)

Some patients may not meet these criteria, but treatment is still desired (eg, patients with severe pain or lesions that may cause strictures). In such patients, the approach to treatment must be individualized given the lack of efficacy data with the available antiviral agents and the potential risks of treatment, such as developing drug-resistance to tecovirimat [6-9] or developing nephrotoxicity or hepatotoxicity with cidofovir or brincidofovir. In the United States, these cases should be discussed with the CDC. For urgent clinical situations, clinicians can contact the CDC Clinical Consultation Team by email ([email protected]) or by phone (770-488-7100).

More detailed information on the specific antiviral agents, including how to obtain tecovirimat in the United States, is found below. (See 'Regimen selection' below and 'Specific agents' below.)

Regimen selection

Approach for most patients — For patients with mpox who warrant antiviral therapy, we suggest tecovirimat given its potential efficacy for treating orthopoxvirus infections in animal models, its safety profile, and accumulating data on treating mpox in humans [3,10-21]. Tecovirimat should be effective for both Clade 1 and Clade 2 infection [22]; however, in one preliminary report, tecovirimat did not reduce the duration of mpox lesions in patients with Clade 1 infection [23]. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Virology'.)

In some countries, such as the United States, tecovirimat is an investigational agent. In the United States, tecovirimat must be obtained through an expanded access program (table 1), as described below. (See 'Tecovirimat' below.)

If tecovirimat (either outside or within a clinical trial) is not available, the decision to treat with an alternative agent such as cidofovir or brincidofovir should be individualized, taking into account the severity of disease, as the risk of complications is greater with these agents (eg, renal failure, liver abnormalities). As an example, in the absence of severe disease, the toxicity of cidofovir and brincidofovir typically outweigh the benefits of the drug. (See 'Cidofovir/brincidofovir' below.)

There are no published data on timing of treatment in humans, but therapy is likely to be most effective when started early in the clinical course, especially in immunocompromised patients. 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 are available.

Considerations in immunocompromised patients — Immunocompromised patients should receive antiviral therapy with tecovirimat since they are at risk for developing severe disease. In the United States, treatment is obtained through an EA-IND in consultation with the CDC (table 1). (See 'Tecovirimat' below.)

In highly immunocompromised patients, combination therapy should be considered (eg, adding cidofovir or brincidofovir to tecovirimat) [24]. As an example, case reports have shown that persons with HIV who have very low CD4 counts (eg, <50 cells/microL) and uncontrolled HIV loads can have a prolonged course of disease, and most mpox deaths are seen in this patient population [25-28]. In addition, there have been reports of viral resistance to tecovirimat developing in highly immunocompromised patients [6,29-31]. However, the decision to use combination therapy must take into account the potential benefits of treatment in those with severe disease as well as the increased risk of adverse events (eg, nephrotoxicity) with an additional agent. (See 'Specific agents' below.)

When initiating treatment, clinicians should assess for drug interactions between tecovirimat and immunosuppressive agents. As an example, tecovirimat may reduce serum concentrations of tacrolimus and sirolimus, so it is important to monitor the levels of these agents [24]. Similarly, there are interactions with certain drugs used to treat HIV. Detailed information on drug interactions with HIV antiretroviral agents is found below. (See 'Persons with HIV' below.)

In addition to using antiviral medications, efforts should be made to improve the patient's immune function. The best chance of curing mpox is with a functional immune system [32]. This includes limiting the use of immunosuppressive medications when possible and initiating antiretroviral therapy (ART) for those with HIV. (See 'Persons with HIV' below.)

After treatment is initiated, patients should be followed closely to ensure medications are taken properly and to monitor the response to therapy. In some immunocompromised patients, a longer duration of tecovirimat (ie, >14 days) is likely needed. (See 'Monitoring response to therapy' below.)

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. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Ocular manifestations'.)

Patients with ocular mpox should be managed in consultation with an ophthalmologist. Treatment should include systemic therapy with tecovirimat. In addition, for those with keratitis, trifluridine should also be considered [33]. 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 [34]. Information on these agents is provided below. (See 'Tecovirimat' below and 'Trifluridine (and vidarabine) eye drops or ointments' below.)

Specific agents — Several antivirals may be useful for the treatment of mpox (tecovirimat, brincidofovir, cidofovir). Some of these drugs were approved for the treatment of smallpox based on animal models and dose and safety studies in healthy humans but are expected to have similar activity for treatment of mpox. Limited data suggest MPXV remains sensitive to all of the approved agents with the exception of infrequent tecovirimat resistance [6-9,35].

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 [36]. In the United States, tecovirimat was approved for the treatment of smallpox in July 2018 [12]. In the United States, tecovirimat remains an investigational agent for treatment of mpox. Information on the use of tecovirimat for treating smallpox is found in a separate topic review. (See "Variola virus (smallpox)", section on 'Tecovirimat'.)

●Obtaining tecovirimat – In some countries (eg, the UK and European Union) tecovirimat is approved for treatment of mpox, whereas in other countries, such as the United States, tecovirimat is still an investigational agent.

In the United States, oral tecovirimat should be obtained under an EA-IND protocol through the CDC (table 1). Previously, patients could obtain tecovirimat through a clinical trial as well but enrollment has closed [37].

Updated information on obtaining tecovirimat in the United States can be found on the CDC website. For urgent clinical situations, clinicians can contact the CDC Clinical Consultation Team by email ([email protected]) or by phone (770-488-7100).

●Dosage and administration – Oral and IV preparations are available. 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 every 12 hours. In persons being treated for HIV, there may be some potential drug interactions that impact the dosing of ART agents. Detailed information on dosing and drug interactions, including dosing in children, is described in the drug information program and the monograph on tecovirimat included within UpToDate.

The duration of treatment is typically 14 days. However, immunocompromised patients may require a longer course of therapy. (See 'Monitoring response to therapy' below.)

When the oral formulation is used, it should be given after a fatty meal to reach optimal absorption and bioavailability.

The IV formulation can be considered in those who are unable to consume a fatty meal but should not be used in patients with severe renal impairment (creatinine clearance [CrCl] <30mL/min). In addition, it 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) [4]. For those who do receive the IV formulation, it can be transitioned to oral therapy once the patient can take oral medications.

●Adverse events – Tecovirimat has generally been well tolerated in persons with pox [3,13,38]. The most frequently reported side effects are headache, nausea, and abdominal pain. In a study that evaluated the safety of tecovirimat in 360 nonpregnant human volunteers as part of the original Food and Drug Administration (FDA) approval process, the adverse effect profile was similar to that of placebo [12].

●Efficacy – Tecovirimat has been found to be effective in treating orthopoxvirus infections in animal models [10,12]. (See "Variola virus (smallpox)", section on 'Tecovirimat'.)

Clinical trials evaluating the efficacy of tecovirimat in humans with pox are ongoing [2,3]. However, in preliminary reports, tecovirimat did not reduce the duration of pox lesions in patients with Clade 1 or Clade 2 infection [23,37].

Several retrospective series and case reports of patients receiving tecovirimat for treatment of mpox have been published [13-21,38]. In one report that included 255 patients who received tecovirimat, the median time to subjective improvement after starting therapy was three days [13]. In another report of 1043 patients in the United States who received tecovirimat under the expanded access program, most patients were started on tecovirimat a median of seven days after illness onset, and recovered by the end of the 14-day course of treatment [38]. There were 40 deaths reported in this group, and almost all occurred in persons with HIV and CD4 counts <200 cells/microL. No conclusions about the efficacy of tecovirimat could be made given the variable nature of the data returned under the expanded access program and the lack of a comparator group.

Cidofovir/brincidofovir — Cidofovir acts as a false nucleotide that is incorporated into the replicating viral DNA by the viral DNA polymerase. Cidofovir has in vitro activity against MPXV and has been shown to be effective against lethal MPXV challenge in animal models [39-41]. During the global outbreak, there were many case reports with the use of cidofovir as a part of combination therapy for mpox in severely immunocompromised patients [8]. 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. When given, it should be used with probenecid to decrease nephrotoxicity. (See "Cidofovir: An overview".)

In June 2021, brincidofovir was approved for use in the United States for treatment of smallpox [42]; it is available through an FDA single-patient emergency investigational drug (EIND) protocol to treat mpox. Brincidofovir is a prodrug of cidofovir that can be given orally and has less nephrotoxicity than cidofovir. (See "Variola virus (smallpox)", section on 'Brincidofovir'.)

The recommended dose of brincidofovir for those ≥48 kg is 200 mg suspension or tablet given once weekly for two weeks. As opposed to tecovirimat, brincidofovir tablets are taken on an empty stomach or with a low-fat meal. Detailed dosing information, including dosing in children, is described in the drug information monograph on brincidofovir included within UpToDate.

There are only limited published data with the use of brincidofovir for treatment of mpox [43,44] since it was not widely available during the height of the 2022 mpox outbreak. Animal models show that it is likely an effective treatment of orthopoxvirus infections [45-47]. However, in one case series, the three patients with mpox who were treated with brincidofovir (200 mg once a week orally) developed elevated liver enzymes resulting in the discontinuation of therapy [14].

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 [48].

Monitoring response to therapy — The standard duration of tecovirimat is 14 days. Although a response to treatment may be seen within four days for many immunocompetent patients [13,49], the full 14-day course of treatment should be completed.

However, some patients may continue to develop lesions despite receiving 14 days of treatment. In addition, lesions that appear to be healing on treatment sometimes progress after stopping tecovirimat [50]. This typically occurs in immunocompromised patients, those not taking their medication, and/or those not taking oral tecovirimat after a fatty meal. When this occurs, these patients should be managed in consultation with an infectious diseases specialist or public health official (eg, the CDC mpox consultation team in the United States).

Management options may include:

●Extending/reinitiating treatment – The duration of tecovirimat can be extended or treatment can be reinitiated on a case-by-case basis. In such patients, it is reasonable to continue tecovirimat until there is clinical improvement with frequent interval evaluations. However, therapy should not be administered beyond 90 days [26]. Patients can continue oral therapy (re-emphasizing the need for a fatty meal for optimal absorption) or switch to the IV formulation). In the United States, these decisions should be made in consultation with the CDC. (See 'Tecovirimat' above.)

Clinicians can also consider adding a second antiviral agent like cidofovir or brincidofovir [26] or vaccinia immune globulin [51]. This approach may be particularly relevant for immunocompromised patients. (See 'Cidofovir/brincidofovir' above and 'Alternatives to vaccination' below.)

●Evaluating for alternative causes – If new lesions are appearing or lesions are progressing after 14 days of tecovirimat, a repeat swab of a lesion should be obtained. If PCR testing is negative for orthopoxvirus, other causes of persistent lesions should be suspected, such as bacterial superinfection. (See 'Management of bacterial superinfection' below.)

Management of bacterial superinfection — 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 — For patients with severe mpox, other treatment modalities may be needed in addition to antiviral therapy. These may include:

●Treatment of balanitis or balanoposthitis causing urethral meatal obstruction. (See "Balanitis in adults", section on 'Management'.)

●Surgical debridement of infected wounds. (See "Surgical management of necrotizing soft tissue infections".)

●Use of corticosteroids in persons with neurologic manifestations, such as encephalitis, edema, or demyelination. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Neurologic manifestations'.)

REDUCING RISK OF EXPOSURE

Infection prevention and control in health care and community settings — Patients typically acquire mpox through close, prolonged, direct contact, and the proper use of infection prevention and control measures can mitigate transmission. The recommendations below are based on guidance from the United States Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) [52,53] as well as experience in our own institutions. Additional recommendations can be found on the CDC website.

This section summarizes our approach to infection prevention and control. More detailed information on transmission of mpox is presented in a separate topic review. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Human-to-human transmission'.)

Health care settings — The identify, isolate, inform framework should be applied to reduce the risk of transmitting mpox in health care settings. This approach has been applied broadly to a variety of pathogens, including high-consequence infectious diseases (HCIDs) such as Ebola virus disease [54] and Middle East respiratory syndrome [55] as well as non-HCIDs, such as measles [56].

●Identify – 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. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)".)

●Isolate – Once identified, clinicians need to ensure the patient with the suspected infection of interest is appropriately isolated. In the health care setting, use of standard precautions are applied to all patients, including individuals being considered for mpox, in addition to transmission-based precautions [57]. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Standard precautions'.)

•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. The patient should wear a facemask for transport outside the room.

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 prophylaxis' 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 (formerly 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.

Considerations for patient placement in individuals who have been exposed to mpox are discussed below. (See 'Monitoring after an exposure' below.)

•Personal protective equipment – Personal protective 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).

The CDC recommends that all HCP 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 [53]. This combination of PPE reflects contact precautions (gown and gloves), droplet precautions (eye protection), and airborne precautions (respiratory protection). Although there is no definitive epidemiologic evidence that mpox is spread by the airborne route, the use of an N95 respirator during routine care ensures that HCP are protected during activities that may result in aerosolization of virus (eg, shaking contaminated linens or performing an aerosol generating procedure). (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Routes of person-to-person transmission'.)

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 2). The approach to monitoring 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 prophylaxis' below.)

•Patient transport – Patient transport outside the room should be limited to that essential for the care of the patient and for procedures or interventions that cannot be performed in the patient room [53]. If transport is necessary, the patient should wear a well-fitting facemask 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 – Most diagnostic samples and clinical waste containing MPXV can be designated as Category B infectious substances [58]. Therefore, bodily fluids such as urine, stool, and blood, sharps, used PPE, and other waste generated in the course of care is managed as routine hospital medical waste.

However, Clade 1 viral cultures (ie, materials containing or contaminated with intentionally propagated virus) are classified as Category A infectious substances since they are expected to contain higher concentrations of virus. In this setting, additional precautions should be taken [59]. This mostly applies to research settings.

●Inform – Once isolated, the next step is to inform, which requires that the clinicians alert other team members that the patient is considered at risk for mpox and 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.

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. 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.)

Individuals with mpox 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 [60]:

●Skin lesions should be covered (eg, long sleeves, long pants) to minimize risk of contact with mpox lesions.

●Patients should avoid sharing their used clothes, towels, food, utensils, or facemasks 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 well-fitting 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.

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.

The CDC provides detailed information on the approach to isolation and prevention of mpox in the community (including disinfection and disposal of contaminated waste).

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 [53,60]. Decisions regarding discontinuation of isolation precautions in the health care facility are often made by facility infection prevention and control; decisions regarding discontinuation of isolation precautions in 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 [52]. MPXV can be found in semen and vaginal fluids and has been transmitted sexually. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Routes of person-to-person transmission'.)

The risk of acquiring mpox through organ, tissue, or blood donation is unknown, and the decision to use a donor with recent mpox or exposure to mpox must be individualized. Some organizations, such as the Red Cross, require patients to wait a minimum of 21 days before donating blood after infection or exposure to mpox. No cases of mpox transmission from blood, tissue, or organ donation were reported through February 2024 [61,62].

Other ways to reduce exposure risk — Persons in communities where there has been substantial transmission of MPXV should try to reduce the risk of new exposures. Although pre- and post-exposure prophylaxis with vaccine likely reduces the risk of developing infection, the efficacy of vaccination during an outbreak has not been established. (See 'Indications for post-exposure vaccination' below.)

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 [63]. Information on strategies to reduce sexual risk can be found on the CDC website.

More detailed information on transmission of MPXV and the use of infection prevention strategies to reduce exposure are discussed elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Global multi-country outbreak' and "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Human-to-human transmission' and 'Infection prevention and control in health care and community settings' above.)

VACCINATION TO PREVENT DISEASE

Types of vaccines — There are two available orthopoxvirus vaccines that can reduce the risk of developing mpox. The modified vaccinia Ankara (MVA) vaccine, which is a non-replicating smallpox and mpox vaccine, (JYNNEOS in the United States, IMVANEX in the European Union, and IMVAMUNE in Canada) and a replication-competent smallpox and mpox vaccine (ACAM2000) vaccine. Vaccination is expected to provide protection regardless of clade [64].

●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. It is now recommended as a routine vaccine in people at risk for mpox.

●ACAM2000 – ACAM2000, a replication-competent smallpox and mpox vaccine, 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 and mpox.

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".)

Pre-exposure prophylaxis with orthopoxvirus vaccines — Certain individuals are at increased risk for mpox 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 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 PrEP should still be monitored after an exposure; however, additional post-exposure vaccination is not indicated. (See 'Post-exposure prophylaxis' below.)

Persons at risk for community acquired infection

●Routine vaccination – In the United States, routine vaccination with the MVA vaccine is recommended for persons aged 18 years and older with any of the following risk factors for community-acquired mpox (figure 1) [65,66]:

•Gay, bisexual, and other men who have sex with men, transgender, or nonbinary people who in the past six months have had one of the following:

-A new diagnosis of ≥1 sexually transmitted disease

-More than one sex partner

-Sex at a commercial sex venue

-Sex in association with a large public event in a geographic area where mpox transmission is occurring

•Sexual partners of persons with the risks described above

•Persons who anticipate experiencing any of these risk factors

Vaccination can also be given to those self-attesting to being eligible for pre-exposure vaccination without specifying a clear indication [67]. 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.

Sexually active teenagers who fall into one of the risk groups can be vaccinated under the Emergency Use Authorization since the MVA vaccine is only approved for use in persons 18 years and older.

Guidelines in other countries may vary. (See 'Society guideline links' below.)

●Vaccination for travelers during an outbreak – The United States CDC recommends the MVA vaccine for persons, regardless of gender identity or sexual orientation, if they are traveling to a country where clade 1 MPXV is spreading between people and they anticipate any of the following [68]:

•Sex with a new partner

•Sex at a commercial sex venue (eg, a sex club or bathhouse)

•Sex in exchange for money, goods, drugs, or other trade

•Sex in association with a large public event (eg, a rave, party, or festival)

It is important that patients complete the two dose MVA vaccine series since data indicate that two doses are better than one [69-74]. For travelers, the mpox vaccine series should be started at least six weeks before travel begins since it takes 14 days after the second dose for immunity to peak [68].

Pre-exposure vaccination reduces the risk of acquiring mpox, and if infection occurs in persons who have completed the vaccination series, the symptoms are less severe [69,73,75,76]. In a study that evaluated 32,819 probable or confirmed mpox cases in the United States between May 11, 2022 and May 1, 2024, only 271 (0.8 percent) occurred in persons who were fully vaccinated [75]. Among those who developed mpox, the symptoms were milder in those who were vaccinated compared to those who were not. In vaccinated patients, mpox cases occurred a median of 266 days after receipt of the second vaccine dose. The median interval between the second vaccine dose and illness onset was longer for persons who received the vaccine intradermally versus subcutaneously (median 363 versus 263 days). (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses", section on 'Dosing and administration'.)

In an earlier study evaluating 9544 cases of mpox that developed between July 31 and October 1, 2022 in the United States, 87 percent occurred in those who were unvaccinated [77]. The incidence of mpox in at-risk unvaccinated persons was 7.4 times greater than those who received one dose of the MVA vaccine ≥14 days earlier and 9.6 times greater than those who received two doses of the MVA vaccine ≥14 days earlier. In this study, there was no apparent difference in protection between subcutaneous and intradermal administration.

Older studies prior to the global mpox outbreak also support the benefit of prior vaccination with replication-competent vaccinia virus vaccines in preventing mpox. In a study of human-to-human transmission of MPXV in Africa, 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, respectively) [57]. In another study that showed an increasing incidence of human mpox cases in Africa [78], 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 [79]. These individuals were unaware that they had been infected because they did not have any recognizable disease symptoms, and no transmission was documented.

Although data suggest that vaccination with MVA or replication-competent vaccinia virus vaccines reduce the risk of developing mpox, the duration of protection from person-to-person spread of mpox in at-risk groups is not yet defined [80-85]. As an example, in May of 2023, a number of cases were noted in persons who received two doses of the MVA vaccine [80]. An investigation of this outbreak that occurred in Chicago revealed that all infections were mild and occurred in people who likely had high level exposure and frequent exposures [86].

Studies looking at antibody titers after immunization with MVA-BN vaccine have also been conducted but have not established the duration of immunologic protection [87]. Some have suggested that duration of higher antibody levels might be enhanced by a longer interval between vaccines [88].

Persons with occupational risk — In 2021, the 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)

●Designated response team members who are at risk for occupational exposure to orthopoxviruses, in consultation with local public health authorities [89]

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. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses", section on 'Vaccinia virus (replication-competent) vaccine'.)

In 2022, the United States CDC approved the updated ACIP smallpox vaccine recommendations related to PrEP with the JYNNEOS vaccine for those at occupational risk, including the use of booster vaccination for those at continued risk or after an exposure [90]. Recommendations for booster doses in those at risk for community and occupational exposures to mpox differ since workers in the laboratory settings have ongoing exposure to the virus and are often working with high titers of virus. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses", section on 'Role of booster doses'.)

Routine pre-exposure vaccination to prevent mpox is not recommended for health care personnel (HCP) because the risk of transmission in the health care setting is low. Most reports of nosocomial transmission have been associated with high-risk exposures from sharps injuries [91-98]. In one report that evaluated 166 community and health care contacts of a patient with mpox, no secondary cases were identified [94]. In another report of 313 HCP exposed to patients with mpox, no cases of mpox developed, even though recommended personal protection equipment (PPE) use and receipt of post-exposure prophylaxis vaccination was low [99]. However, post-exposure vaccination with the MVA vaccine should be offered to all HCP after a high-risk exposure and as part of shared decision making for some intermediate-risk exposures. (See 'Indications for post-exposure vaccination' below.)

Post-exposure prophylaxis — Individuals with an exposure to mpox should monitor for symptoms. (See 'Monitoring after an exposure' below.)

The need for post-exposure prophylaxis (PEP) with vaccine depends upon the risk of the exposure (table 2). (See 'Indications for post-exposure vaccination' below.)

Exposure definition and risk stratification — Exposures in both community and health care settings should be assessed to determine the risk of MPXV transmission. The United States CDC defines exposures as high, intermediate, or uncertain to minimal risk, and no identifiable risk, as described in the table (table 2) [100]. 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), if appropriate PPE was used, and in some cases, the duration of the interaction.

However, exposures may be recategorized to a particular risk level at the discretion of public health authorities or health care facilities involved in the evaluation of the exposure. 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 [101,102].

Individual institutions may coordinate their response to exposures 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.

Indications for post-exposure vaccination — Certain individuals should be offered PEP with one of the available orthopoxvirus vaccines. The indications for PEP are typically dictated by public health authorities and depend upon the exposure risk (table 2). 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 [103]. Community engagement programs, including those that focus on racial and ethnic underrepresented groups, can help reduce health disparities in PEP access [104,105].

In general, PEP is not needed for individuals who were diagnosed with mpox during the outbreak that started in May of 2022, since mpox likely confers immune protection. For those who received two doses of MVA vaccine, the need for a booster dose after an exposure has not been established, but at present it is not routinely recommended.

For others, our approach is as follows and is consistent with guidelines from the CDC [53,106]:

●High risk exposure – For most individuals who have had a known or suspected high-risk exposure to mpox (table 2), we suggest post-exposure vaccination with the MVA vaccine, a non-replicating smallpox and mpox vaccine.

If the MVA vaccine is not available, ACAM2000, a replication-competent smallpox and mpox vaccine, 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 since the risks associated with vaccination may be greater than those associated with mpox. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses", section on 'Vaccinia virus (replication-competent) vaccine' and "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Prognosis and risk for severe disease'.)

●Intermediate risk exposure – For individuals with intermediate-risk exposures (table 2), the need for PEP should be determined on a case-by-case basis evaluating the likelihood of transmission from the specific exposure versus the risks of vaccination. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses".)

●Uncertain to minimal risk exposure – Post-exposure vaccination is not indicated for those with a uncertain to minimal risk exposure.

The risks and benefits of vaccination in persons who are pregnant or breastfeeding are outlined below. (See 'Persons who are pregnant or lactating' 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 after an exposure. Recommendations for vaccination from different public health agencies (eg, CDC, World Health Organization [WHO], UKHSA) may vary [101,102].

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. In addition, persons should continue to reduce their risk of exposure. (See 'Other ways to reduce exposure risk' above and 'Infection prevention and control in health care and community settings' above.)

Post-exposure vaccination for orthopoxvirus diseases is based on the observation that post-exposure vaccination could prevent or modify the course of smallpox illness. Although the efficacy of PEP during the 2022 outbreak has not yet been established and has been difficult to study using real world data [107], 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 [57,108,109]. However, it is not known how many individuals were exposed and not given PEP.

Among those who develop mpox after post-exposure vaccination, most cases have occurred soon after the first dose of the vaccine was administered, suggesting that the vaccine was given at a time when it could not prevent disease [110-112]. As an example, in a study that followed 7339 individuals who received the MVA vaccine, 69 of the 90 patients who developed mpox did so within the first 14 days of receiving their first dose [110]. However, rare breakthrough cases were also reported, as two patients in this study developed mpox more than 14 days after receiving the second vaccine dose.

Alternatives to vaccination — In some settings, alternatives to post-exposure vaccination should be considered (eg, patients with contraindications to vaccination and/or patients unlikely to respond to the vaccine).

●Vaccinia immune globulin – The use of intravenous (IV) vaccinia immune globulin (VIG) may be considered in highly immunocompromised patients or infants with an exposure history. Immunization with replication-competent vaccinia virus vaccine is contraindicated [113], 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 ([email protected]) 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 in consultation with the CDC since access to tecovirimat in the United States is limited since it is an investigational drug. Clinicians can contact the CDC Clinical Consultation Team by email ([email protected])or by phone (770-488-7100) for urgent clinical situations.

MONITORING AFTER AN EXPOSURE

Individuals who remain asymptomatic — Individuals with a high or intermediate risk of exposure should monitor for symptoms for 21 days after their last exposure (table 2) [106]. Monitoring after an uncertain or minimal risk of exposure is at the discretion of public health authorities and health care facilities. The clinical manifestations of mpox are described in a separate topic review. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Clinical manifestations'.)

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).

In community settings, contacts who remain asymptomatic can continue routine daily activities. In health care settings, the United States Centers for Disease Control and Prevention (CDC) states that exposed patients who are asymptomatic generally do not need to be isolated, with some exceptions (eg, patients who are unable to communicate about symptom onset) [106]. However, when resources allow, some health care facilities may choose to isolate all patients with confirmed mpox exposures during the 21-day exposure window. (See 'Post-exposure prophylaxis' above.)

Exposed individuals should generally refrain from donating blood, cells, tissue, breast milk, or semen, although organ donation may be considered after an appropriate risk-benefit consideration from individuals who are asymptomatic after exposure with no evidence of infection [106].

If symptoms develop — Exposed individuals should be isolated immediately if they develop signs and symptoms consistent with mpox (eg, fever, headache, myalgias, lymphadenopathy, rash). (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Clinical manifestations'.)

Such patients should use the same types of precautions as described above. (See 'Health care settings' above and 'Community settings' above.)

●Individuals who develop a rash consistent with mpox should undergo diagnostic testing. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Evaluation and diagnosis'.)

Those with mpox should continue precautions using the criteria described above. (See 'When to discontinue isolation' above.)

●Individuals without a rash who have other signs and symptoms that could be consistent with mpox (eg, flu-like symptoms) can discontinue isolation if five days have passed without developing any new symptoms and a thorough skin and oral examination reveals no changes [53,60].

SPECIAL POPULATIONS

Persons who are pregnant or lactating — Pregnant persons who are diagnosed with mpox or have had an exposure to mpox should be managed in consultation with an infectious diseases specialist, if possible.

●Understanding risks of disease during pregnancy — When managing pregnant patients with mpox or after an exposure to mpox, clinicians must take into account the risks to the pregnant person, the fetus, and the newborn.

•Severe disease during pregnancy – Pregnant persons with mpox tend to have similar clinical manifestations as those who are not. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Clinical manifestations'.)

Historically, disease is felt to be more severe during pregnancy [114]. However, during the global outbreak that started in May 2022, which was due to clade 2 virus, this did not appear to be the case [115].

•Adverse outcomes to fetus and newborn – MPXV can cross the placenta and can lead to adverse pregnancy outcomes in up to 50 percent of cases [116]. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Risk of transmission in different settings'.)

Available data looking at pregnancy outcomes in persons with Clade 1 virus suggest mpox during pregnancy is associated with a high risk of miscarriage, intrauterine fetal demise, and vertical transmission [117]. In a series evaluating eight pregnancies between 2023 to 2024 during the outbreak in the Democratic Republic of the Congo (DRC), four had either miscarriages or stillbirth, representing a 50 percent fetal loss rate [118]. In a report that evaluated fetal outcomes in four pregnant patients with mpox infection in the DRC between 2007 and 2011, two patients with moderate/severe disease had spontaneous first-trimester pregnancy losses (pregnancy tissue was not tested for infection) [119]. 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 mpox, 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 [120].

Some studies suggest that pregnancy outcomes may be less severe in the setting of clade 2 infection. In one report that identified 10 cases during the global outbreak in 2022, vertical transmission was not reported [115]. However, in another report that included pregnancy outcomes in nine persons, there were 3 pregnancy losses (<20 weeks gestation) and 6 live births; two of six liveborn infants had a rash within ten days of birth and tested positive for mpox [121].

●Management of persons exposed to mpox in pregnancy – Persons who are pregnant should be offered post-exposure vaccination with the modified vaccinia Ankara (MVA) vaccine if indicated, as described above. (See 'Indications for post-exposure vaccination' above.)

The risks and benefits of vaccination in persons who are pregnant or breastfeeding are outlined on the CDC website. Key considerations used in shared decision-making should include:

•Risk of infection after an exposure. (See 'Exposure definition and risk stratification' above.)

•Risk of severe disease during pregnancy and adverse pregnancy outcomes, as described above.

•Risk of vaccination. There are currently no US Food and Drug Administration (FDA)-approved mpox vaccines for persons who are pregnant. 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 an increased risk of miscarriage, birth defects, preterm birth, or fetal vaccinia [122,123].

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.

●Management of persons with confirmed mpox infection in pregnancy

•Antiviral therapy – The United States CDC guidance suggests antiviral treatment with tecovirimat for symptomatic pregnant and lactating persons with mpox. Treatment should be administered through an expanded access investigational new drug (EA-IND) protocol. (See 'Tecovirimat' above.)

The recommendation for treatment is based on concerns for an increased risk of severe disease affecting the pregnant person during pregnancy, the risk of transmitting monkeypox virus (MPXV) to the fetus during pregnancy or to the newborn during and after birth, and the risk of severe infection in the newborn, if infected [116,124], as described above.

Limited available data on the use of tecovirimat in pregnancy suggest that it is well tolerated [114,116,125,126]. In a meta-analysis that included seven observational studies with 21 children and 12 pregnant individuals, there were no serious adverse events reported [116]. Similarly, in preliminary data from a trial in the DRC evaluating the safety and efficacy of tecovirimat in 600 children and adults with clade 1 mpox (including persons who are pregnant), there was no difference in adverse events between the placebo and antiviral groups, although there was no improvement in the time to lesion resolution among those who received tecovirimat [23,114]. 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. Clinical trials evaluating the use of tecovirimat during pregnancy are underway [126]. (See 'Antiviral therapy' above.)

The use of alternative agents is less clear. In general, cidofovir and brincidofovir should not be used to treat mpox in people during the first trimester of pregnancy since animal studies showed evidence of teratogenicity [124]. It is not known whether vaccinia immune globulin (VIG) can cause fetal harm when administered during pregnancy, although other immune globulins have been safely administered.

Discussions regarding antiviral treatment should employ a shared-decision making model between patient and provider that incorporates the potential risks of the illness to pregnancy and pregnant patients and the available data on the safety and efficacy of treatment in a pregnant population.

•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 test results [127]. Fetal ultrasound examination at regular intervals until delivery has been suggested by some experts as a prudent approach since so little is known about the natural history of mpox in pregnancy.

•Considerations for delivery – The timing of delivery is based on standard obstetric indications [128]; however, the optimal route of delivery is unclear. Cesarean birth has been recommended for patients with genital lesions to reduce the risk of intrapartum transmission, but the benefit is unknown since antepartum transmission may have occurred.

•Reducing transmission risk after birth – Uninfected newborns born to an infected parent should be isolated from other newborns [129]. The infected parent should also be restricted from interactions with their uninfected newborn until they are determined to no longer be infectious, given the risk of severe illness if the newborn were to develop mpox. (See 'When to discontinue isolation' above.)

Exceptions to restricting interactions between parent 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. It is not certain whether MPXV can be transmitted through the breast milk of the infected parent versus the close contact associated with direct feeding at the breast.

Children and adolescents — Data on children with mpox are limited [130]. Although there is evidence that the disease is more severe in children younger than eight years infected with clade 1 of MPXV, there is less experience with clade 2. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Virology' and "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Africa'.)

●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) [131]. Antiviral therapy should also be considered for those felt to be at increased risk for severe disease (eg, persons <18 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 intravenous (IV) cidofovir [132].

●Prevention – Post-exposure vaccination with the MVA vaccine should be considered for those >6 months of age after a high-risk exposure [129]. Although the MVA vaccine is not approved for those younger than 18, there are no known contraindications.

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 was recognized in May 2022, 30 to 50 percent of patients have had concomitant HIV [133-135]. It is not known if HIV infection increases a person's risk of acquiring mpox after exposure. However, people with advanced HIV are at increased risk of severe disease related to mpox [26]. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Complications in immunocompromised patients'.)

For persons with HIV who have mpox, anti-viral therapy should be used in those who are immunocompromised and at risk for severe disease (eg, CD4 count <200 cells/microL) [24,136,137]. In one report of 112 people with HIV, those treated with tecovirimat within seven days of symptom onset were less likely to progress to severe disease compared to those who were treated after seven days or who did not receive tecovirimat (5.4 versus 26.8 percent; paired odds ratio, 13.00 [95% CI, 1.71-99.40]) [138]. (See 'Antiviral therapy' above and 'Considerations in immunocompromised patients' above.)

For those taking antiretroviral therapy (ART), ART should be continued [139]. For persons with newly diagnosed HIV and those who are not taking ART, we suggest that ART be started/restarted as soon as possible. Although cases of immune reconstitution inflammatory syndrome (IRIS) have been described in the setting of starting ART [140], pending additional data, the benefit of immune recovery following ART initiation appears to outweigh the risk of IRIS [141]. 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 between tecovirimat and certain antiretroviral 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 needed [142,143]. However, cabotegravir-rilpivirine should not be initiated during tecovirimat therapy or for two weeks after tecovirimat has been completed [143]. (See "Use of long-acting cabotegravir-rilpivirine in people with HIV".)

Vaccination with the MVA vaccine should be administered to those who warrant prophylaxis, regardless of their CD4 count [142]. This includes pre-exposure prophylaxis (PrEP) for those at risk for acquiring infection and post-exposure prophylaxis (PEP) for those who have been exposed (see 'Post-exposure prophylaxis' above). Patients with CD4 counts >350 cells/microL had antibody responses after MVA vaccination similar to non-HIV-infected patients [144]. In another study that included patients with HIV and CD4 counts between 200 and 350 cells/microL, antibody responses were present but lower than non-HIV-infected patients [145].

The ACAM2000 vaccine, a replication-competent smallpox and mpox vaccine, is generally contraindicated in persons with uncontrolled HIV since the risks generally outweigh the benefits of vaccination [146]. However, while it has not been widely used during the global outbreak that started in 2022, 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 5^th to 6^th 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 10^th to 12^th 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 mpox)".)

SUMMARY AND RECOMMENDATIONS

●Causative agent – Monkeypox virus (MPXV), 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.)

Most cases have occurred in Central and West Africa. However, in 2022, a global multi-country outbreak involved thousands of individuals in previously nonendemic countries. Specific outbreaks are discussed in a separate topic review. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)".)

Patients with mpox typically develop a distinctive rash, but it can also be similar in appearance to some other viral infections (eg, herpes simplex virus infection, varicella-zoster virus infection). (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)".)

●Patient management

•Patients with severe disease or risk factors for severe disease – We suggest antiviral therapy with tecovirimat for individuals with or at risk for severe disease (table 1) and those with lesions in the eyes (Grade 2C). Limited data suggest tecovirimat is well tolerated and may shorten the duration of viral shedding. In the United States, tecovirimat is still an investigational drug, and such patients must obtain tecovirimat through an expanded-access investigational new drug protocol.

If tecovirimat is not available, the decision to use an alternative agent (eg, cidofovir) must be determined on a case-by-case basis taking into account the severity of disease and the potential side effects (eg, nephrotoxicity, hepatotoxicity). (See 'Indications' above and 'Regimen selection' above and 'Specific agents' above.)

•Additional considerations in immunocompromised patients – In immunocompromised patients, efforts should be made to restore immune function, in addition to antiviral therapy. This may involve reducing the dose of immunosuppressive therapy, if possible. (See 'Considerations in immunocompromised patients' above.)

For persons with HIV, we suggest antiretroviral therapy (ART) be initiated as soon as possible (Grade 2C). Although cases of immune reconstitution inflammatory syndrome (IRIS) have been seen in persons with mpox who initiate ART, the benefit of immune recovery appears to outweigh the risks of IRIS. (See 'Persons with HIV' above.)

For those with severe disease who are significantly immunocompromised (eg, persons with HIV who have CD4 counts <200 cells/microL and uncontrolled HIV loads), combination therapy with tecovirimat plus another agent (eg, cidofovir or brincidofovir) should be considered, taking into account the potential increased risk of adverse events with these additional agents. (See 'Considerations in immunocompromised patients' above and 'Specific agents' above.)

•Patients without severe disease – Immunocompetent patients with mpox typically have mild disease and recover with supportive care. (See 'Supportive care' above.)

However, treatment may still be desired for some patients with non-severe disease who are not at high-risk for complications. This includes patients with severe pain or lesions that may cause strictures. In these patients, the approach to treatment must be individualized given the lack of efficacy data for treatment of mpox and the potential risks of tecovirimat (eg, developing drug-resistance ); in the United States, these patients should be discussed with the CDC. Alternative agents (eg, cidofovir or brincidofovir) are generally avoided in this setting given their toxicity. (See 'Indications' above and 'Regimen selection' above.)

●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 in health care and community settings' above.)

•In the health care setting – 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.)

Patients should be placed in a single-person (private) room; special air handling is generally not required; however, an airborne infection isolation room (AIIR) should be used if differential diagnosis includes other pathogens for which an AIIR is indicated (eg, those with suspected varicella) and/or if aerosol-generating procedures (eg, intubation) are anticipated to be performed.

•In the community setting – Patients with mpox who are cared for at home should be isolated in a room or area separate from other family members. This is particularly important for persons with extensive lesions that cannot be easily covered. Additional precautions are described above. (See 'Community settings' above.)

•When to discontinue precautions – 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 (See 'When to discontinue isolation' above.)

●Pre-exposure prophylaxis – For selected persons at high risk for mpox due to behavioral or occupational risk factors, we suggest pre-exposure prophylaxis (PrEP) with the MVA vaccine (Grade 2C). Pre-exposure vaccination reduces the risk of acquiring mpox and if infection occurs in persons who are fully vaccinated, the symptoms are less severe. This approach is consistent with recommendations from the Advisory Committee on Immunization Practices (ACIP). (See 'Pre-exposure prophylaxis with orthopoxvirus vaccines' above.)

●Post-exposure management

•Monitoring – All individuals with confirmed exposures to mpox (table 2) should monitor for signs and 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 high, intermediate, uncertain to minimal risk, or no identifiable risk (table 2). (See 'Exposure definition and risk stratification' above.)

-Known or suspected high-risk exposure – For most individuals 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 'Post-exposure prophylaxis' above.)

However, PEP is generally not needed for individuals who were diagnosed with mpox during the outbreak that started in May of 2022, since mpox likely confers immune protection. For those who received two doses of MVA vaccine, the need for a booster dose after an exposure has not been established, but at present is not routinely recommended.

-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 for post-exposure vaccination' 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 'Persons who are pregnant or lactating' above and 'Children and adolescents' above and 'Persons with HIV' above.)