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Importance听 A global outbreak of clade IIb Monkeypox virus (MPXV) infections spread rapidly across at least 118 countries resulting in a Public Health Emergency of International Concern (PHEIC) from July 2022 to May 2023. This outbreak affected more than 99鈥�000 persons worldwide and caused more than 33鈥�000 infections and 60 deaths in the US. In 2024, there have been approximately 200 new infections per month in the US. On August 14, 2024, the World Health Organization declared mpox a PHEIC for a second time due to a rapid increase in infections with clade I MPXV in Central Africa.

Observations听 Mpox is primarily acquired through direct skin to skin contact with MPXV. With clade IIb MPXV, infections are most commonly associated with sexual activity among individuals who are gay, bisexual, and other men who have sex with men. After a median incubation period of 7 to 10 days, prodromal symptoms include fever (62%-72%), lymphadenopathy (56%-86%), myalgias (31%-55%), malaise (23%-57%), and headache (25%-55%). Skin lesions progress through 4 well-defined stages (macules, papules, vesicles, and pustules) over 2 to 4 weeks. Clade IIb MPXV is typically a self-limited illness with a low mortality rate (<0.2% in the US); however, severe illness and death may occur in immunocompromised individuals, especially those with advanced HIV (CD4 count鈥�<200 cells/渭L). Mpox should be suspected in patients with potential exposure to MPXV who have skin lesions, and the diagnosis is confirmed with polymerase chain reaction testing of lesions. Management is supportive and focuses on skin care and symptom relief with analgesics. While no antiviral treatments are currently approved for mpox by the US Food and Drug Administration, several therapeutics, such as tecovirimat, brincidofovir, and vaccinia immune globulin intravenous, are available through expanded access programs or clinical trials. Vaccination with the 2-dose Modified Vaccinia Ankara-Bavarian Nordic vaccine is recommended for high-incidence populations and has an efficacy of 66% to 86%.

Conclusions and Relevance听 Mpox is a viral infection transmitted primarily through close skin to skin contact that typically causes a self-resolving illness but can result in severe illness and death in immunocompromised individuals. First-line therapy is supportive care, although patients with severe mpox infection may be treated with advanced therapeutics. Mpox vaccination is effective and, if available, should be offered to individuals at risk of exposure to mpox.

Mpox (formerly known as monkeypox) is caused by Monkeypox virus (MPXV), a zoonotic orthopoxvirus closely related to variola and vaccinia viruses and first discovered in 1958 in a colony of research monkeys. The first human case was described in 1970 in the Democratic Republic of Congo. MPXV is a double-stranded DNA virus with a large genome (200 kilobase) encoding for 191 proteins. There are 2 main clades (distinct genetic lineages or subgroups) of the virus that have evolved from a common ancestral virus. Clade I is endemic to Central African countries and is historically associated with more severe disease; clade II is endemic to West African countries and historically associated with milder disease.¹

In 2022, mpox caused by clade IIb MPXV spread worldwide, with the first confirmed case outside of endemic areas reported on May 6, 2022, and the first reported case in the US on May 17, 2022. Since then, more than 99鈥�000 mpox clade IIb cases have been recorded across at least 118 countries, with more than 33鈥�000 of these cases and 60 deaths in the US.² The clade II MPXV outbreak has predominantly occurred among individuals who are gay, bisexual, and other men who have sex with men, and 38% of cases have occurred in patients with HIV; however, infections in the US have been reported in individuals of all ages, sexes, genders, and sexual orientations.^3,4

The clade II MPXV outbreak peaked outside of Africa in the summer of 2022, and the World Health Organization (WHO) declared its Public Health Emergency of International Concern (PHEIC) over on May 10, 2023.⁵ By summer 2024, mpox in the US was limited to approximately 200 reported cases monthly. However, the WHO declared a second PHEIC for mpox on August 14, 2024, due to a rapid increase in infections with clade I MPXV in Central Africa.⁵

Prior to the 2022 mpox outbreak, research on mpox had been limited. The worldwide spread of clade IIb MPXV has provided increased information about this disease.⁶ This review discusses the epidemiology, transmission, clinical presentation, assessment and diagnosis, prognosis, management and treatment, and prevention of mpox. Key questions and answers for clinicians are listed in Box 1.

Box Section Ref ID

A PubMed search was performed for English-language publications of mpox or monkeypox published between January 1, 1975, and September 13, 2024. A total of 5168 abstracts were identified. We prioritized the inclusion of recent, high-quality evidence such as randomized clinical trials and observational longitudinal studies with larger sample sizes and longer follow-up periods. Governmental websites were searched to identify current mpox topic recommendations where published evidence was unavailable. A total of 111 citations were included, consisting of 1 randomized clinical trial, 59 observational studies, 9 basic science articles, 23 reviews, 13 government website pages, 4 case reports, 1 conference abstract, and 1 press release.

The MPXV reservoir is thought to be arboreal rodents in African rainforests; most likely the squirrel Funisciurus anerythrus.⁷ MPXV can be transmitted from animals to humans through direct contact with infected lesions, bodily fluids, bites, scratches, contaminated fomites such as linens and clothing, and respiratory droplets and aerosols. Close human to human contact has been the major driver of these outbreaks. Transmission via contaminated fomites and exposure to respiratory secretions are not major contributors.^8,9 While replication-competent MPXV has been found in the respiratory tract, there is no current evidence of human outbreaks in persons with shared airspace without direct contact with the virus.⁹ Contact tracing of 113 cases associated with 221 commercial flights has resulted in no identified mpox infections.¹⁰ In human to human transmission, the virus primarily spreads through direct prolonged contact with an infected person鈥檚 lesions or bodily fluids.^9,11 There is also evidence that infected individuals can transmit the virus before exhibiting mpox symptoms and that asymptomatic transmission of MPXV may contribute to the spread of disease.^12-14 Acquisition of mpox through laboratory work is rare and has occurred primarily through needle-stick injuries, direct contact with an mpox specimen, or potentially through aerosols generated from laboratory procedures.

The transmission of MPXV primarily occurs when the virus enters the host through direct exposure to skin or mucosal surfaces, including oral, anogenital, or ocular tissues. The virus infects resident immune cells and local lymph nodes and rapidly replicates,¹⁵ enabling the virus to spread through the lymphatic system and the bloodstream and disseminate to multiple organs.¹⁵

No nosocomial infections of hospitalized patients have been reported in the US, but nosocomial transmission has occurred in Africa.¹⁶ A systematic review reported only 10 cases of nosocomial transmission to clinicians worldwide during the 2022 global outbreak, occurring primarily through injuries with sharp objects such as scalpels or needles.¹⁷ Transmission to health care workers during the clade IIb outbreak has rarely occurred even when proper personal protective equipment (gown, gloves, eye protection, N95 respirator) was not used. Data from a facility in Colorado showed that despite low personal protective equipment usage and limited use of postexposure prophylaxis vaccination, none of 313 clinicians exposed in the course of routine patient care acquired mpox.¹⁸

Patients presenting for medical care who are suspected of having mpox should be placed in a single room and standard cleaning and disinfection procedures should be performed after the visit using an Environmental Protection Agency鈥搑egistered hospital-grade disinfectant with an emerging viral pathogen claim.¹⁹ Patients with mpox do not require airborne isolation. Nonhospitalized patients with mpox or suspected mpox should isolate at home. If mpox infection is confirmed, individuals should remain in isolation until all lesions have healed and reepithelialized.

Prior to 2022, cases outside of Africa were rare and typically linked to international travel or the importation of infected animals. However, the 2022 global outbreak of clade IIb was largely spread through sexual transmission and contained in the sexual networks of individuals who are gay, bisexual, and other men who have sex with men. Over the past several months, subclade Ib has emerged in the South Kivu province of the Democratic Republic of the Congo (DRC); its rapid human to human transmission has occurred through close contact within households as well as sexual contact among both heterosexual people in addition to individuals who are gay, bisexual, and other men who have sex with men.²⁰

Mpox can vary widely from a mild, self-limiting illness to a severe disease with life-threatening complications in immunocompromised individuals.^21-23 While the mean incubation period of mpox ranges from 2 to 21 days, the mean incubation period during the clade IIb outbreak, characterized largely by sexual transmission, typically ranged from 7 to 10 days.^24-28

Following an asymptomatic incubation period, patients with mpox typically have a prodrome of symptoms for 1 to 5 days including fever (62%-72%), lymphadenopathy (56%-86%), myalgias (31%-55%), malaise (23%-57%), and headache (25%-55%)^24,27-33 before the appearance of a rash.²³ However, during the 2022 clade IIb outbreak, the timing of prodromal symptoms was variable, occurring before, during, or after the appearance of the rash or other presenting symptoms (eg, proctitis).^28,30

The characteristic clinical feature of mpox is painful skin lesions that uniformly progress through 4 well-defined stages over 2 to 4 weeks, as shown in the Figure. Lesions typically begin as macules and evolve into papules, vesicles, and pustules, which crust and desquamate in the final stage. People with mpox are infectious from the onset of clinical symptoms until all skin lesions have reepithelialized, typically taking up to 4 weeks.

The mpox rash classically occurs in a centrifugal distribution, with lesions involving the face, trunk, and limbs. However, transmission through sexual contact, as observed in the recent global outbreak, has frequently caused genital and anogenital (36%-73%) and perioral and oral skin lesions (14%-25%), associated painful lesions at any mucosal site, nonuniform progression of lesions (eg, different stages of lesions side by side), and limited (median number of 10) lesions.^27,28,30,34 Mpox has also presented with other complications, including proctitis (14%-36%), pharyngitis (13%-36%), urethritis, and ocular disease.^27,28,30,34 Less than 5% of patients with mpox present with a single skin lesion without other symptoms or with mucosal symptoms (proctitis/pharyngitis) without skin lesions.^23,24,26 Localized single lesions at the point of a needle-stick injury have also been described in health care workers.³⁵

Mpox can cause complications, such as necrotizing skin lesions with bacterial superinfection, pneumonia, and encephalitis, particularly in immunocompromised individuals such as those with advanced HIV (CD4 count鈥�<200 cells/渭L). Abnormal liver function test results are common, seen in more than one-third of hospitalized patients with mpox.³⁶ Compared with immunocompetent individuals, people with advanced HIV or solid organ transplants have a higher likelihood of developing multiorgan involvement with mpox infection, resulting in a substantially higher need for hospitalization and increased risk of death.^37-40 This increased susceptibility to severe disease is due in part to an inadequate innate immune response characterized by impaired natural killer cell and T-lymphocyte function and inadequate B-cell responses, which are important to clear the virus.⁴⁰

More severe mpox infections have been described in young children and pregnant individuals in clade I outbreaks; however, fewer cases from these groups have been described in the clade IIb outbreak.^{23,24,31,41-43}

The diagnosis of mpox should be suspected in patients with skin lesions and known or possible exposure to MPXV. The typical appearance includes painful skin lesions covering multiple regions in any of the 4 stages previously described, while an atypical presentation includes exanthem and/or a single, painless, or ulcerated lesion. Diagnostic confirmation is achieved through molecular DNA amplification techniques of samples collected from lesions to detect MPXV. For initial testing of suspected mpox, a nonvariola orthopoxvirus polymerase chain reaction (PCR) test of skin lesions is frequently used. Confirmatory, clade-specific testing, which can be performed by the US Centers for Disease Control and Prevention (CDC), should be considered if the initial test result is positive or inconclusive. In the US, mpox is a reportable disease to local health departments.

The CDC recommends that clinicians wear a gown, gloves, eye protection, and an N95 respirator while testing for mpox to protect against viral transmission.¹⁹ At least 2 skin lesions should be sampled from separate sites, if possible, using a sterile synthetic swab. The lesion must be vigorously swabbed to ensure an adequate collection of viral DNA; unroofing or aspiration of lesions with a scalpel or needle tip is not advised due to the risk of self-injury. Swabs may be stored dry or in virus transport media, as specified by the diagnostic laboratory.⁴⁴

Several reverse transcriptase PCR testing options are available in the US for detecting the clade II virus. These tests use primers and probes that target highly conserved regions of the viral genome.⁴⁵ Patients who test positive on a screening orthopoxvirus PCR test and negative on a clade II鈥搒pecific PCR test may have a clade I MPXV infection or infection with another less common pathogenic orthopoxvirus infection such as cowpox or Borealpox (formerly Alaskapox). In such cases, samples should be forwarded to a reference laboratory, such as the CDC, for further testing. Viral culture and phenotyping assays to determine antiviral susceptibility are not routinely performed for clinical care but may be performed for epidemiological and research purposes.

In 2023, the US Food and Drug Administration (FDA) authorized point-of-care testing modalities, including real-time PCR tests for clade IIb and nonvariola orthopoxvirus, on a commercial platform that performs as well as laboratory-based assays.^46,47 These point-of-care tests provide rapid results (typically within 36 minutes) and are especially useful during outbreaks because they require minimal training. Furthermore, on April 10, 2024, the FDA granted Emergency Use Authorization for a home self-collection sampling kit, which may help overcome barriers to testing and the stigma associated with mpox testing.⁴⁸

Orthopoxvirus serology testing is rarely performed because of the increased likelihood for false-positive results due to cross-reactivity with other orthopoxviruses. Positive serology could represent prior exposure to the vaccinia virus either through vaccination with available smallpox or mpox vaccines, many of which were administered during the 2022 mpox outbreak, or from a previous infection or active infection with another orthopox virus.⁴⁹

The differential for mpox includes several other infections that involve skin and mucosal lesions. Secondary syphilis may present with a generalized rash and mucocutaneous lesions, but unlike mpox, these lesions are generally painless. Herpes simplex virus can present with painful vesicular lesions, particularly in the anogenital area, which may resemble mpox. Other skin and soft tissue infections, such as impetigo or cellulitis, can present with pustular or vesicular lesions that may appear similar to mpox.⁵⁰ In children and occasionally adults, enteroviral infection, molluscum contagiosum, varicella-zoster virus, and other orthopoxviruses should be considered in the differential diagnosis of mpox.

Most individuals with mpox experience a self-limiting illness and typically recover fully within 2 to 4 weeks after onset of symptoms. After healing, mpox skin lesions can leave scars (5%-40% of people infected with mpox), potentially causing stigmatizing cosmetic effects and more commonly affecting those with advanced HIV.^51-53 Genital lesions due to mpox may result in long-term complications such as scarring and strictures in anogenital areas, which can significantly affect quality of life and sexual function.⁵¹ Ocular involvement is a serious complication of mpox and can sometimes result in partial vision loss or even blindness, therefore, early ophthalmology evaluation is encouraged.⁵⁴ Less common complications may include urethral strictures and paraphimosis, as well as rectal perforations, fistulas, and strictures.^27,30,55-57 In these cases, involvement of urology and colorectal surgery specialists may be beneficial.

The mortality rate during the clade IIb global outbreak from 2022 to the present has been low in high-income countries (<0.2% in the US).² However, the overall mortality rate in prior mpox outbreaks in Africa was 4.6% and data from the DRC showed a mortality rate of 1.67% in the context of optimal supportive medical care, including nutrition, hydration, and treatment for secondary infections.^58,59 This disparity in outcomes between the US and countries in Africa may be due to better access to supportive care and nutrition in high-income countries. Additionally, prior outbreaks in Africa have disproportionately affected children, who may be more vulnerable to severe disease outcomes.³¹

The severity of mpox and its clinical outcomes are influenced by virus-specific virulence factors and immune escape properties, as well as by host immune status and response to infection. Severity can be challenging to compare across clades and between outbreaks occurring in different locations due to differences in baseline health and access to health care services among affected populations. However, compared with clade IIb, infections with the clade I virus are associated with a more severe disease course, and higher mortality rates (up to 10%) have been reported during outbreaks in the DRC.^8,23,47-49 Experimental studies in small animal models using different viral subclades (clade I, clade IIa, and clade IIb) have demonstrated these differences in virulence across clades (Table 1).^60,61

While no treatments are specifically approved by the FDA for mpox, several antiviral medications used for other orthopoxviruses have been used for patients with severe mpox infections.

Most patients with mpox experience pain due to skin and mucosal lesions. The CDC offers guidance for supportive care and pain management.⁶² Oral medications, such as acetaminophen or nonsteroidal anti-inflammatory drugs, are recommended for pain control. Patients with mpox who have more severe pain may be treated with gabapentinoids or short courses of opioids.^63,64 Stool softeners help decrease painful bowel movements associated with proctitis. Topical treatments, such as sitz baths or lidocaine gels for proctitis and saltwater or viscous lidocaine gargles for pharyngitis, may decrease pain. For suspected bacterial superinfection of mpox lesions, topical or systemic antibiotics indicated for skin and soft tissue infections are advised (Table 2).

All individuals assessed for mpox should also be screened for sexually transmitted infections (gonorrhea, chlamydia, syphilis, and HIV) because of the high incidence of coinfection reported in multiple cohorts during the 2022 mpox outbreak.^{3,4,28-30,34,38}

Currently, there are no FDA-approved treatments for mpox. Several agents have been used for mpox that were approved for smallpox through the FDA Animal Rule, which allows efficacy findings from animal studies when human trials are not ethical or feasible (Table 3).

Tecovirimat, which is FDA approved for smallpox through the Animal Rule, targets the p37 protein, which is involved in development of the viral envelope required for replication in orthopoxviruses. In the US, more than 7000 individuals with mpox have received tecovirimat under an Expanded Access for an Investigational New Drug (EA-IND) protocol, with limited available safety data indicating only mild adverse effects.⁶⁵ Observational data on the effectiveness of tecovirimat has shown mixed results.^66-69 In 2024, a randomized, placebo-controlled, double-blind trial evaluating the safety and efficacy of oral tecovirimat for the treatment of mpox was completed; preliminary results indicated that tecovirimat did not reduce the duration of mpox lesions among 597 children and adults with clade I MPXV in the DRC.⁵⁸ Tecovirimat is available for treatment of mpox for all patients in the US through the Study of Tecovirimat for Human Mpox Virus (STOMP) clinical trial, and through a CDC EA-IND for those with severe disease or at risk of severe disease.⁶² Phenotypic resistance (reduced activity) to tecovirimat has been described most commonly among immunocompromised patients receiving prolonged courses of treatment, likely due to tecovirimat resistance mutations in the F13L gene of the mpox virus, which is crucial for viral maturation and dissemination.⁷⁰ Transmitted drug resistance has also been observed.^70-72

Cidofovir and its prodrug brincidofovir are antiviral medications that inhibit DNA polymerase activity and, thus, DNA replication. Although no randomized efficacy data exist in humans, animal models suggest that brincidofovir may be effective against orthopoxviruses, including mpox. Data for cidofovir use are extrapolated from the data for brincidofovir.⁷³

Intravenous cidofovir has been used to treat highly immunosuppressed patients with severe mpox disease.⁷³ Cidofovir has also been used topically as a cream for skin lesions or directly injected into skin lesions, with some case studies reporting clinical improvement.⁷⁴ Cidofovir is FDA approved for cytomegalovirus retinitis and therefore is widely available in the US and several other high-income countries for off-label use.

Brincidofovir, a prodrug of cidofovir, is less nephrotoxic. Its adverse effects are primarily transaminitis and diarrhea, which can interfere with the absorption of oral medications.⁷⁵ Animal studies have suggested that brincidofovir alone may be effective, and in vitro there may also be a synergistic effect when combined with tecovirimat.⁷⁶ Brincidofovir is FDA approved for smallpox, but is available for treatment of mpox through an FDA Emergency Use IND (E-IND).⁶² The CDC recommends consideration of combination therapy with tecovirimat and brincidofovir for severely immunocompromised individuals with severe mpox infection.⁷³

Vaccinia immune globulin intravenous (VIGIV) treatment is the administration of antibodies targeting vaccinia virus, which may provide activity against the MPXV virus. There are no published data currently available on the effectiveness of VIGIV for the treatment of mpox virus in humans. VIGIV may be considered for patients with severe mpox and advanced HIV, who may be unable to produce an adequate antibody response to infection.^73,77 VIGIV is available for the treatment of mpox through a CDC EA-IND.⁶²

The topical antiviral agent trifluridine has in vitro activity against orthopoxviruses and has been provided to patients with mpox ocular disease, although there are limited observational data on its efficacy.⁷⁸

Combinations of these treatments have been used in severely ill patients with mpox; however, no clinical trial data have demonstrated the effectiveness of combination therapies for mpox.

After the start of the 2022 mpox outbreak, people vulnerable to mpox infection, particularly individuals who are gay, bisexual, and other men who have sex with men, adjusted their behaviors to reduce mpox transmission, including reducing the number of sexual partners and frequency of sexual encounters.⁷⁸ Modeling data suggest that the 2022 outbreak was slowed first through self-protective behavioral changes among populations with increased exposure risk, followed by vaccination.⁷⁸

Two vaccines have been approved by the FDA and are available for the prevention of mpox in adults: ACAM2000, a second-generation, replication-competent, single-dose smallpox vaccine and Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN; also known as IMVANEX, IMVAMUNE, and JYNNEOS), a third-generation, replication-limited smallpox and mpox vaccine.⁷⁹ The MVA-BN vaccine (JYNNEOS), which became commercially available in the US in April 2024, is administered subcutaneously or intradermally in 2 doses given 4 weeks apart. Due to its high cost, MVA-BN access has been limited for individuals who do not have insurance or are underinsured in the US, and access to mpox vaccine has also been very limited in low- and middle-income countries, including those with large and emerging mpox outbreaks. In September 2024, the WHO announced MVA-BN as the first vaccine against mpox to be included in its prequalification list, which will accelerate procurement of mpox vaccines by governments and international agencies and is expected to increase access to mpox vaccinations in low- and middle-income countries.⁸⁰

The Advisory Committee on Immunization Practices recommends vaccination with the 2-dose series of MVA-BN as preexposure prophylaxis for people aged 18 years and older at nonoccupational risk for mpox,⁸¹ including people who are gay, bisexual, and other men who have sex with men, as well as transgender or nonbinary people, who in the past 6 months have been newly diagnosed with 1 or more sexually transmitted diseases, had multiple sex partners, engaged in sex at a commercial venue or during a large public event in an area where mpox transmission is occurring, or are sexual partners of those who meet these criteria. This also applies to individuals who anticipate engaging in any of these activities. There are no recommendations from the Advisory Committee on Immunization Practices regarding mpox vaccination booster doses for those with nonoccupational risk of exposure (Box 2).

Box Section Ref ID

MVA-BN and ACAM2000 can be used for preexposure prophylaxis vaccination for people at occupational risk for exposure to mpox, such as laboratory workers. Individuals at risk of occupational exposure (laboratory setting) are advised to receive an MVA-BN booster every 2 years or an ACAM2000 booster every 3 years.⁷⁹ Vaccination is not routinely recommended for clinicians providing care for patients with mpox who have access to appropriate personal protective equipment.⁷⁹

A growing body of evidence indicates that while vaccination is not fully protective against mpox, breakthrough infections tend to be milder and are less likely to lead to hospitalization or death (Table 4).^82-85 Vaccination with the 2-dose MVA-BN vaccine is recommended for specific populations and has an efficacy rate of 66% to 86% (Box 2).^86-100 Long-term vaccine effectiveness and duration of immunity provided by MVA-BN against mpox remain uncertain.¹⁰¹

The CDC recommends MVA-BN vaccination as postexposure prophylaxis for people with known or presumed exposure to mpox, ideally administered within 4 days of exposure but can be given up to 14 days after exposure. There are limited observational data on the effectiveness of postexposure prophylaxis vaccination for mpox.^102,103

While mpox clade IIb MPXV infections in Europe and North America have decreased from the peak in the summer of 2022, several African countries continue to have frequent and large outbreaks of mpox and the emergence of new viral clades. In 2024, the DRC experienced the largest recorded outbreak of clade I MPXV, with more than 21鈥�000 suspected cases and more than 700 deaths.¹⁰⁴ This outbreak includes a cluster of cases involving sexual transmission of the clade I virus, creating concern for widespread transmission through social and sexual contact similar to the clade IIb outbreak in 2022 but mostly involving heterosexual networks, although spread among people who are gay, bisexual, and other men who have sex with men has also been reported.⁵¹

A recent investigation into a cluster of mpox cases in eastern DRC from September 2023 to January 2024 identified a novel emerging strain named clade Ib.^105,106 This strain shows significant genetic divergence from clade Ia viral sequences isolated from previous outbreaks with accumulation of apolipoprotein B editing complex (APOBEC3)鈥搈ediated mutations, suggesting that direct transmission between humans, rather than animal to human transmission, is becoming the predominant mode of spread for mpox in large outbreaks.^106-108 The emergence of clade Ib MPXV and its rapid spread in the DRC and neighboring countries (Burundi, Kenya, Rwanda, and Uganda) underscores the need for heightened surveillance and global vaccine equity to mitigate an ongoing public health crisis.¹⁰⁹ In response to this global health concern, in August 2024, the WHO declared mpox a PHEIC. As of August 25, 2024, clade Ib cases were reported in Sweden (n鈥�=鈥�1) and Thailand (n鈥�=鈥�1) after travel to Africa.¹¹⁰

This review has several limitations. First, the quality of the included literature was not formally evaluated. Second, some relevant studies may have been missed. Third, it does not cover all aspects of mpox transmission, clinical presentation, assessment and diagnosis, prognosis, management and treatment, and prevention. Fourth, mpox is rapidly evolving.

Mpox is a viral infection transmitted primarily through close skin contact that typically causes a self-resolving illness but can result in severe illness and death in immunocompromised individuals. First-line therapy is supportive care, although patients with severe mpox infection may be treated with advanced therapeutics. Mpox vaccination is effective and, if available, should be offered to individuals at risk of exposure to mpox. Mpox is an evolving global health threat, and clinicians must be aware of characteristic signs and symptoms of mpox to ensure timely diagnosis and appropriate management.

Accepted for Publication: September 19, 2024.

Published Online: October 14, 2024. doi:10.1001/jama.2024.21091

Corresponding Author: Jason Zucker, MD, MS, Division of Infectious Diseases, Columbia University Irving Medical Center, 622 W 168th St, 8th Floor, New York, NY 10032 (Jz2700@cumc.columbia.edu).

Conflict of Interest Disclosures: Dr Titanji reported receiving grants from the National Institutes of Health鈥檚 Building Interdisciplinary Research Careers in Women鈥檚 Health and Emory Center for AIDS Research. Dr Zucker reported receiving grants from the Centers for Disease Control and Prevention and serving as vice chair of the STOMP trial. No other disclosures were reported.

Additional Contributions: We thank Stephanie Galitano, MD, Columbia University Vagelos College of Physicians and Surgeons, for her gracious effort in reviewing images for the figure.