Mpox Available

The presentation of mpox (formerly known as monkeypox) is similar to but milder than that of smallpox, prior to its eradication.

Classic mpox infection generally involves a prodromal illness that may last several days and is characterized by fever, lymphadenopathy, malaise, sore throat, and headache, followed by the development of a characteristic diffuse rash. The rash typically involves many lesions, begins on the face, and spreads to other parts of the body including the extremities (often with involvement of palms and soles) and trunk. Generally, there are more lesions on the face and extremities than the trunk (centrifugal distribution). Classically, lesions begin as macules that progress to papules, firm vesicles, and deep-seated pustules, which can develop central umbilication and be painful until the healing phase begins. The lesions are typically in the same stage of evolution in a particular area on the body. Crusting and resolution occur over a period of 2 to 4 weeks. Lymphadenopathy in the submandibular, cervical, axillary, or inguinal regions usually occurs during the prodromal period or, rarely, with rash onset. An enanthem characterized by oral lesions on the tongue and other areas of the mouth may develop shortly before the appearance of cutaneous lesions. Ocular involvement can lead to keratitis, corneal scarring, and blindness. Other complications can include vomiting and diarrhea leading to severe dehydration, pneumonia, encephalitis, sepsis, hemorrhagic lesions, bacterial skin infection, pregnancy loss, congenital infection, and preterm delivery. Deaths have occurred. Coinfections, including with varicella zoster virus, have been reported.

In May 2022, a global outbreak of mpox began, primarily infecting men who have sex with men. Most people infected with mpox virus in this outbreak had mild or absent prodromal symptoms. Occasionally, one or more prodromal symptoms (eg, fever, lymphadenopathy, malaise, sore throat, headache) developed concurrently with the onset of skin lesions. Lesions varied in size, and for some patients were much smaller than those associated with classic mpox and were fewer in number (ie, a single lesion or a few scattered lesions). In many cases, the rash was prominent in the anogenital region and associated with proctitis and rectal complaints (eg, severe rectal pain, tenesmus). Lesions in differing stages of rash progression occurred side-by-side. Fulminant and fatal infection occurred in persons with severe immunocompromise, including uncontrolled human immunodeficiency virus (HIV) infection.

Mpox is typically self-limited and resolves over 2 to 4 weeks. It can be confused with other illnesses, particularly varicella. Generally, varicella in children is not associated with a febrile prodrome or prominent lymphadenopathy, both of which can occur with mpox, particularly the classic clinical presentation of mpox. Mpox lesions develop into firm pustules, and historically (although not always) are in the same stage in the same area of the body, whereas varicella is in multiple stages of rash in the same area. Classic mpox lesions are typically more prominent on the face and extremities, versus varicella, which typically has a higher number of lesions on the trunk. Other common pediatric conditions that can be confused with mpox include hand, foot, and mouth disease; molluscum contagiosum; scabies; insect bites; allergic reactions; and drug eruptions. Genital or perianal lesions can look similar to a variety of sexually transmitted infections (STIs) (eg, syphilis, herpes simplex virus, lymphogranuloma venereum), and people have been coinfected with mpox virus and other STIs.

Monkeypox virus, which causes mpox disease, is a member of the Poxviridae family (genus Orthopoxvirus). Other members of this genus that can infect humans include cowpox virus, vaccinia virus, and smallpox (variola).

Mpox virus has 2 clades. Clade I (previously called the Congo Basin clade of mpox virus) is associated with a 11% case fatality rate in Africa in individuals without prior smallpox vaccination. Clade II (previously called the West African clade of mpox virus) is associated with a 1% case fatality rate in Africa. Clade IIb was associated with the 2022 global mpox outbreak. Disease severity, regardless of clade, is believed to be increased in pregnant people, young children, people who have atopic dermatitis and other exfoliative skin conditions, and people who are immunocompromised. The classic presentation of mpox has occurred after exposures to either clade in central and west African countries where mpox virus is endemic.

Mpox virus is spread most commonly by direct contact with lesion material, body fluids, or indirectly via fomites, such as contaminated clothing and bedding. It can also be spread by respiratory secretions, occurring when there is exposure to saliva and possibly prolonged face to face contact. A person is considered infectious from prodromal illness onset until all skin lesion crusts have fallen off and a new layer of skin has formed. The animal reservoir for classic mpox has not yet been determined, although small mammals, including rodents, are suspected; humans and other nonhuman primates can be infected and present with disease. Mpox can be acquired by the scratch or bite of an infected animal, through exposure to contaminated animal products, or through fomites (eg, shared towels and bedding).

During the 2022 global mpox outbreak, cases in adolescents were reported resulting from sexual contact; nonsexual transmission also occurred. Cases in children younger than 12 years occurred in the setting of skin-to-skin contact with a household member with mpox during routine caregiving activities (an instance of fomite transmission through shared towels was also reported). No anogenital lesions were reported among the 28 children younger than 12 years of age.¹⁷⁴ 

The incubation period for mpox is 3 to 17 days (average, 5–13 days).

Mpox virus can be detected in a swab of a lesion or a lesion crust or exudate (unroofing or aspirating a lesion is not recommended) by Orthopoxvirus or mpox-specific nucleic acid amplification tests (NAATs). Diagnostic testing is available through the US Laboratory Response Network (LRN), through consultation with state or local public health departments, and through some commercial laboratories. A positive NAAT result for Orthopoxvirus in the epidemiologic setting of a known mpox outbreak may be treated as a presumptive case, if collected from a patient with a compatible clinical presentation and epidemiologic risk factors. Specimens can also be sent to the Centers for Disease Control and Prevention (CDC) for mpox virus-specific characterization, including a NAAT assay specific for mpox virus, immunohistochemistry in tissue for Orthopoxvirus, serology for Orthopoxvirus, and genetic sequencing. Anti-Orthopoxvirus immunoglobulin M may be useful to diagnose mpox in a patient 4 to 56 days after rash onset who has not been vaccinated with a smallpox or mpox vaccine within the past 60 days.

Testing for other STIs and HIV should be performed for patients with anogenital lesions as coinfections occur.

Most patients with mpox have self-limited disease. Patients should be counseled not to touch their eyes. Patients with ocular or periorbital lesions should be treated promptly because of the risk of developing keratitis and potentially permanent visual problems; these patients should have a consultation with an ophthalmologist regarding management and discussion of ocular therapy, such as topical trifluridine. Patients with severe disease (eg, hemorrhagic disease, confluent lesions, secondary bacterial infections, sepsis, encephalitis, lesions on the penile foreskin or strictures involving the urethral meatus, or severe involvement of other anatomic areas including anorectal lesions interfering with bowel movements, oral lesions associated with severe dysphagia, or other complicated or severe conditions, including conditions requiring hospitalization) and those at risk for severe disease (eg, patients with immunocompromising conditions, patients who are pregnant or breastfeeding, children younger than 1 year, patients with a condition affecting skin integrity) should also be considered for antiviral treatment. Management of patients with severe or complicated disease or those at risk for severe disease should be discussed with an expert in infectious diseases.

Pain can be severe, particularly when there are genital, rectal, or anal lesions. A variety of over-the-counter treatment modalities, including sitz baths, can be helpful. Information on pain management in mpox infections is described at www.cdc.gov/poxvirus/mpox/clinicians/pain-management.html.

Guidance is available from the CDC (www.cdc.gov/poxvirus/mpox/clinicians/treatment.html and www.cdc.gov/poxvirus/monkeypox/clinicians/people-with-HIV.html). Tecovirimat (TPOXX or ST-246) was approved by the US Food and Drug Administration (FDA) for the treatment of smallpox and has been shown to be active against mpox virus in animal models; it is the preferred treatment for mpox patients who would benefit from antivirals. As of August 2023, tecovirimat is available through an expanded access investigational new drug (EA-IND) protocol for intravenous treatment of mpox for those who weigh at least 3 kg and for oral administration for those who weigh at least 13 kg (see www.accessdata.fda.gov/drugsatfda_docs/label/2022/214518s000lbl.pdf; www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html#anchor_1655488137245; and Table 4.10, p 1044). At least weekly monitoring of renal function is indicated in children and adolescents receiving intravenous tecovirimat.

Vaccinia immune globulin intravenous (VIGIV) is licensed for the treatment of complications of vaccinia vaccination; effectiveness for mpox is unknown. The CDC has an EA-IND for use in mpox (www.fda.gov/media/78174/download). To discuss use of VIGIV, the CDC clinical consultation team can be accessed by email ([email protected]) or if urgent, through the CDC Emergency Operations Center (770-488-7100).

Brincidofovir (a lipophilic derivative of cidofovir that can be given orally and does not appear to have renal toxicity) has been approved for smallpox treatment. There is an FDA-authorized single patient emergency use IND for brincidofovir for mpox (www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html#anchor_1655488353796 and www.accessdata.fda.gov/drugsatfda_docs/label/2021/214460s000,214461s000lbl.pdf). It can be used in patients who have significant progression on tecovirimat, develop recrudescence of disease after initial improvement on tecovirimat, or have a contraindication for tecovirimat (see Table 4.10, p 1044).

Cidofovir is licensed for treatment of cytomegalovirus retinitis in patients with AIDS, is commercially available, and has activity against orthopoxviruses in studies, but the effectiveness for treating people with severe mpox is unknown. It has dose-dependent nephrotoxicity (www.accessdata.fda.gov/drugsatfda_docs/label/1999/020638s003lbl.pdf).

A patient suspected of having mpox should be placed in a private room, and a health care professional should use a National Institute for Occupational Safety and Health-approved particulate respirator equipped with an N95 or higher respirator, gown, gloves, and eye protection. If an aerosol-generating procedure is performed, the patient should be placed in a private room equipped with negative-pressure ventilation with high-efficiency particulate air filtration. Good hand hygiene should be practiced, and extreme care should be taken with materials that may have been contaminated by the patient’s lesions, crusts, or body fluids, so as not to create aerosols or contaminate additional items. Hospital infection control personnel and the state (and/or local) health department should be notified about the patient.

Mpox patients who do not require hospitalization can be isolated at home. General guidance on isolation and mpox is available on the CDC website (www.cdc.gov/poxvirus/mpox/clinicians/infection-control-home.html and www.cdc.gov/poxvirus/mpox/clinicians/isolation-procedures.html). During the infectious period, an infected patient should avoid contact with others when possible, and with pets. Ideally, one person should provide care to an infected child. The caregiver should wear a respirator or well-fitting mask when caring for the patient, cover areas of broken skin with bandages and clothing to the extent possible, and avoid direct skin-to-skin contact with the rash. The caregiver should wear gloves when changing bandages or when skin contact may occur. Gloves should be disposed of after each use, followed by handwashing. If any clothing (whether on the caregiver or the child) comes into contact with the rash, it should be laundered. Patients 2 years and older should wear a well-fitting mask, and lesions should be covered when interacting with the caregiver (or other in the household). Skin lesions should be covered when possible. Additional information, including information on laundering and cleaning is available on the CDC website (www.cdc.gov/poxvirus/mpox/clinicians/pediatric.html and www.cdc.gov/poxvirus/mpox/if-sick/cleaning-disinfecting.html).

Laboratory workers handling mpox specimens or a member of a high-risk group, as identified by public health, may be eligible for vaccination and for booster doses. Recommendations from the CDC Advisory Committee on Immunization Practices (ACIP) are available.¹⁷⁵ 

JYNNEOS is a live, nonreplicating vaccinia vaccine that was approved by the FDA in 2019 for the prevention of mpox and smallpox in persons 18 years or older who are at high risk for mpox. It is given as a 2-dose series, separated by 28 days. It has an emergency use authorization (EUA) for use in children younger than 18 years (www.fda.gov/media/160774/download). There is also an EUA for intradermal dosing and administration in patients 18 years or older. In October 2023, the ACIP voted to recommend vaccination with the 2-dose JYNNEOS vaccine series for persons aged 18 years and older at risk for mpox, defined as: 1) gay, bisexual, and other men who have sex with men, transgender, or nonbinary people who in the past 6 months have had a new diagnosis of ≥1 sexually transmitted infection, more than one sex partner, sex at a commercial sex venue, or sex in association with a large public event in a geographic area where mpox transmission is occurring; 2) sexual partners of persons with the risks described in above; or 3) persons who anticipate experiencing any of the above.

ACAM2000 is a licensed live, replicating vaccinia virus vaccine to prevent smallpox and may be used to protect against mpox under FDA’s EA-IND mechanism. It is a lyophilized, single-dose vaccine (for primary administration) that requires a bifurcated needle for administration. Inadvertent transmission of the vaccine virus from ACAM2000 may occur from vaccine recipients to their household contacts. Children who are immunocompromised or have atopic skin disease are at increased risk of serious complications following contact transmission, including progressive vaccinia and eczema vaccinatum. Information on these vaccines can be found on the CDC website (www.cdc.gov/poxvirus/mpox/clinicians/vaccines/vaccine-considerations.html). Detailed information about contraindications to preexposure smallpox immunization and adverse reactions to vaccination can be found in the ACAM2000 package insert and medication guide (www.fda.gov/vaccines-blood-biologics/vaccines/acam2000). VIGIV, available through the CDC, is licensed for certain complications of ACAM2000 vaccination (www.cdc.gov/smallpox/clinicians/vaccine-medical-management6.html). CDC medical staff can be reached through the CDC emergency operations center at 770-488-7100.

Cases of febrile rash illness for which mpox is considered should be reported to state or local health departments, who will investigate potential contacts and provide recommendations that may include symptom monitoring for 21 days and postexposure prophylaxis. Asymptomatic exposed persons do not need to quarantine but should monitor for symptoms.

Postexposure immunization within 4 days of exposure with JYNNEOS or ACAM2000 vaccines may prevent mpox. If unable to vaccinate within that time, vaccinating up 14 days after exposure may still provide protection against severe disease. State and local health officials should be consulted on the use of vaccine for exposed individuals.

Infants born to people with suspected or confirmed mpox should undergo early bathing and postexposure prophylaxis. Although the optimal strategy for postexposure prophylaxis of newborn infants born to infected persons has not been defined, VIGIV should be considered, and consultation with an expert in pediatric infectious diseases is recommended. Infants should stay in a separate room and not have direct contact with parent(s) or caregivers infected with mpox virus. Breastfeeding should be delayed during the isolation period of the breastfeeding parent, and human milk should be pumped and discarded. Neonates should be monitored closely for signs of mpox (eg, fever, lymphadenopathy, rash, symptoms of illness) for 21 days following birth/contact with the infected person. Monitoring should include daily temperature checks and full skin examinations. This monitoring can be performed by a health care professional or the person taking care of the neonate. Additional recommendations are available at www.cdc.gov/poxvirus/mpox/clinicians/pediatric.html.

Mpox is a nationally notifiable disease and should be reported immediately to the state or local health department.