BACKGROUND: Borealpox virus (BRPV, formerly known as Alaskapox virus) is a zoonotic member of the Orthopoxvirus genus first identified in a person in 2015. In the six patients with infection previously observed BRPV involved mild, self-limiting illness. We report the first fatal BRPV infection in an immunosuppressed patient. METHODS: A man aged 69 years from Alaska's Kenai Peninsula was receiving anti-CD20 therapy for chronic lymphocytic leukemia. He presented to care for a tender, red papule in his right axilla with increasing induration and pain. The patient failed to respond to multiple prescribed antibiotic regimens and was hospitalized 65 days postsymptom onset for progression of presumed infectious cellulitis. BRPV was eventually detected through orthopoxvirus real-time polymerase chain reaction testing of mucosal swabs. He received combination antiviral therapy, including 21 days of intravenous tecovirimat, intravenous vaccinia immunoglobulin, and oral brincidofovir. Serial serology was conducted on specimens obtained posttreatment initiation. FINDINGS: The patient's condition initially improved with plaque recession, reduced erythema, and epithelization around the axillary lesion beginning one-week post-therapy. He later exhibited delayed wound healing, malnutrition, acute renal failure, and respiratory failure. He died 138 days postsymptom onset. Serologic testing revealed no evidence the patient generated a humoral immune response. No secondary cases were detected. CONCLUSION: This report demonstrates that BRPV can cause overwhelming disseminated infection in certain immunocompromised patients. Based on the patient's initial response, early BRPV identification and antiviral therapies might have been beneficial. These therapies, in combination with optimized immune function, should be considered for patients at risk for manifestations of BRPV.

A global outbreak of clade II mpox associated with sexual contact, disproportionately affecting gay, bisexual, and other men who have sex with men (MSM), has been ongoing since May 2022. Information on types of contact most associated with transmission is limited. This report used data from a multijurisdictional vaccine effectiveness case-control study of sexually active persons aged 18-49 years who identified as MSM or transgender, collected during August 2022-July 2023. Odds of mpox associated with selected types of intimate and nonintimate close contact with a person with mpox were estimated. Among 457 case-patients and 1,030 control patients who met minimum data requirements, 150 (32.8%) case-patients and 57 (5.5%) control patients reported close contact with a person with mpox and were included in this analysis. Adjusted odds of mpox were 5.4 times as high among those who reported having condomless receptive anal sex with a person with mpox, compared with participants who reported close contact with a person with mpox and no condomless receptive anal sex with that person (OR = 5.4; p = 0.031). Although the mpox vaccine is highly effective, vaccination coverage remains low; a multifaceted approach to prevention remains important and should include vaccination promotion, safer sex practices, and increasing awareness that mpox continues to circulate.

We used cross-sectional data from 226 patients with monkeypox virus to investigate the association between anatomic exposure site and lesion development. Penile, anorectal, and oral exposures predicted lesion presence at correlating anatomic sites. Exposure site also predicted the first lesion site of the penis and anus.

Monkeypox virus (MPXV) can spread among humans through direct contact with lesions, scabs, or saliva; via respiratory secretions; and indirectly from fomites; via percutaneous injuries; and by crossing the placenta to the fetus during pregnancy. Since 2022, most patients with mpox in the United States have experienced painful skin lesions, and some have had severe illness. During 2021-2022, CDC initiated aircraft contact investigations after receiving reports of travelers on commercial flights with probable or confirmed mpox during their infectious period. Data were collected 1) during 2021, when two isolated clade II mpox cases not linked to an outbreak were imported into the United States by international travelers and 2) for flights arriving in or traveling within the United States during April 30-August 2, 2022, after a global clade II mpox outbreak was detected in May 2022. A total of 113 persons (100 passengers and 13 crew members) traveled on 221 flights while they were infectious with mpox. CDC developed definitions for aircraft contacts based on proximity to mpox cases and flight duration, sent information about these contacts to U.S. health departments, and received outcome information for 1,046 (68%) of 1,538 contacts. No traveler was found to have acquired mpox via a U.S. flight exposure. For persons with mpox and their contacts who had departed from the United States, CDC forwarded contact information as well as details about the exposure event to destination countries to facilitate their own public health investigations. Findings from these aircraft contact investigations suggest that traveling on a flight with a person with mpox does not appear to constitute an exposure risk or warrant routine contact tracing activities. Nonetheless, CDC recommends that persons with mpox isolate and delay travel until they are no longer infectious.

BACKGROUND: After months of few mpox cases, an increase in cases was reported in Chicago during May 2023, predominantly among fully vaccinated (FV) patients. We investigated the outbreak scope, differences between vaccinated and unvaccinated patients, and hypotheses for monkeypox virus (MPXV) infection after vaccination. METHODS: We interviewed patients and reviewed medical records to assess demographic, behavioral, and clinical characteristics; mpox vaccine status; and vaccine administration routes. We evaluated serum antibody levels after infection and compared patient viral genomes with MPXV sequences in available databases. We discussed potential vaccine compromise with partners who manufactured, handled, and administered the vaccine associated with breakthrough infections. RESULTS: During 18 March-27 June 2023, we identified 49 mpox cases; 57% of these mpox patients were FV. FV patients received both JYNNEOS doses subcutaneously (57%), intradermally (7%), or via heterologous administration (36%). FV patients had more median sex partners (3; interquartile range [IQR] = 1-4) versus not fully vaccinated patients (1; IQR = 1-2). Thirty-six of 37 sequenced specimens belonged to lineage B.1.20 of clade IIb MPXV, which did not demonstrate any amino acid changes relative to B.1, the predominant lineage from May 2022. Vaccinated patients demonstrated expected humoral antibody responses; none were hospitalized. No vaccine storage excursions were identified. Approximately 63% of people at risk for mpox in Chicago were FV during this period. CONCLUSIONS: Our investigation indicated that cases were likely due to frequent behaviors associated with mpox transmission, even with relatively high vaccine effectiveness and vaccine coverage. Cases after vaccination might occur in similar populations.

Two doses of JYNNEOS vaccine are effective in preventing many mpox cases and can reduce the severity of symptoms in infected persons. However, infections among fully vaccinated persons can occur. During May 2022-May 2024, a total of 271 mpox cases among fully vaccinated persons were reported to CDC from 27 U.S. jurisdictions. These reported infections are estimated to have occurred in <1% of fully vaccinated persons. Compared with cases among unvaccinated persons, infections among fully vaccinated persons were more likely to occur among non-Hispanic White men aged 30-39 years, were associated with increased numbers of sexual partners, and resulted in less severe disease (p<0.001). Among infections in fully vaccinated persons with complete data, infections after vaccination were reported more commonly after receipt of heterologous (subcutaneous and intradermal) (46%) or homologous subcutaneous (32%) JYNNEOS vaccination than after homologous intradermal (22%) vaccination. Disparate time intervals from vaccination to infection among fully vaccinated persons suggest that immunity is not waning. The median interval between the second vaccine dose and illness onset was longer for cases among persons who had received 2 intradermal doses (median = 363 days; IQR = 221-444 days) compared with cases in persons who had received 2 subcutaneous doses (median = 263 days; IQR = 47-334 days) (p<0.001). The implications of this finding are not known; however, these data should increase confidence in the effectiveness of vaccine doses that were administered intradermally, the preferred method of administration during the peak of the outbreak when vaccine supply was limited. Persons recommended to receive the JYNNEOS vaccine should receive 2 doses, irrespective of the route of administration, and at this time, additional doses are not recommended for the affected population.

Clade I monkeypox virus (MPXV), which can cause severe illness in more people than clade II MPXVs, is endemic in the Democratic Republic of the Congo (DRC), but the country has experienced an increase in suspected cases during 2023-2024. In light of the 2022 global outbreak of clade II mpox, the increase in suspected clade I cases in DRC raises concerns that the virus could spread to other countries and underscores the importance of coordinated, urgent global action to support DRC's efforts to contain the virus. To date, no cases of clade I mpox have been detected outside of countries in Central Africa where the virus is endemic. CDC and other partners are working to support DRC's response. In addition, CDC is enhancing U.S. preparedness by raising awareness, strengthening surveillance, expanding diagnostic testing capacity for clade I MPXV, ensuring appropriate specimen handling and waste management, emphasizing the importance of appropriate medical treatment, and communicating guidance on the recommended contact tracing, containment, behavior modification, and vaccination strategies.

Incidence of human monkeypox (mpox) has been increasing in West and Central Africa, including in the Democratic Republic of Congo (DRC), where monkeypox virus (MPXV) is endemic. Most estimates of the pathogen's transmissibility in the DRC are based on data from the 1980s. Amid the global 2022 mpox outbreak, new estimates are needed to characterize the virus' epidemic potential and inform outbreak control strategies. We used the R package vimes to identify clusters of laboratory-confirmed mpox cases in Tshuapa Province, DRC. Cases with both temporal and spatial data were assigned to clusters based on the disease's serial interval and spatial kernel. We used the size of the clusters to infer the effective reproduction number, Rt, and the rate of zoonotic spillover of MPXV into the human population. Out of 1,463 confirmed mpox cases reported in Tshuapa Province between 2013 and 2017, 878 had both date of symptom onset and a location with geographic coordinates. Results include an estimated Rt of 0.82 (95% CI: 0.79-0.85) and a rate of 132 (95% CI: 122-143) spillovers per year assuming a reporting rate of 25%. This estimate of Rt is larger than most previous estimates. One potential explanation for this result is that Rt could have increased in the DRC over time owing to declining population-level immunity conferred by smallpox vaccination, which was discontinued around 1982. Rt could be overestimated if our assumption of one spillover event per cluster does not hold. Our results are consistent with increased transmissibility of MPXV in Tshuapa Province.

Monkeypox virus (MPXV) is a re-emerging virus of global concern. An outbreak of Clade I MPXV affected 20 captive chimpanzees in Cameroon in 2016. We describe the epidemiology, virology, phylogenetics, and clinical progression of this outbreak. Clinical signs included exanthema, facial swelling, peri-laryngeal swelling, and eschar. Mpox can be lethal in captive chimpanzees with death likely resulting from respiratory complications. We advise avoiding anesthesia in animals with respiratory signs to reduce the likelihood of death. This outbreak presented a risk to animal care staff. There is a need for increased awareness and a One Health approach to preparation for outbreaks in wildlife rescue centers in primate range states where MPXV occurs. Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures.

The extent to which the 2022 mpox outbreak has affected persons without a recent history of male-to-male sexual contact (MMSC) is not well understood. During November 1-December 14, 2022, CDC partnered with six jurisdictional health departments to characterize possible exposures among mpox patients aged ≥18 years who did not report MMSC during the 3 weeks preceding symptom onset. Among 52 patients included in the analysis, 14 (27%) had a known exposure to a person with mpox, including sexual activity and other close intimate contact (eight) and household contact (six). Among 38 (73%) patients with no known exposure to a person with mpox, self-reported activities before illness onset included sexual activity and other close intimate contact (17; 45%), close face-to-face contact (14; 37%), attending large social gatherings (11; 29%), and being in occupational settings involving close skin-to-skin contact (10; 26%). These findings suggest that sexual activity remains an important route of mpox exposure among patients who do not report MMSC.

Approximately 6 months before an unprecedented global mpox outbreak was first identified in the United Kingdom, an adult man was diagnosed with mpox in Maryland, USA [1]. At the time of the investigation, the case was only the eighth monkeypox virus (MPXV) infection diagnosed in a non-African country during the preceding 3 years, all of which were associated with recent travel to Nigeria [2]. One of these 8 imported cases occurred in Texas, USA four months earlier; that case exhibited features clinically consistent with those classically reported in Africa (i.e., large and diffuse lesions, high fever and prodromal symptoms, umbilicated lesions in the same stage of development on specific anatomic surfaces) [3]. In contrast, the Maryland case was milder in severity and had signs that, at the time, were considered unusual for mpox. Several aspects of the Maryland case are noteworthy and in retrospect may offer clues to the origins of the 2022 global mpox outbreak, as well as explain how mpox might have spread undetected before emerging as a global outbreak.

Incidence of human mpox has been increasing in West and Central Africa, including in the Democratic Republic of Congo (DRC), where monkeypox virus (MPXV) is endemic. Most estimates of the pathogen's transmissibility in DRC are based on data from the 1980s. Amid the global 2022 mpox outbreak, new estimates are needed to characterize the virus' epidemic potential and inform outbreak control strategies. We used the R package vimes to identify clusters of laboratory-confirmed mpox cases in Tshuapa Province, DRC. Cases with both temporal and spatial data were assigned to clusters based on the disease's serial interval and spatial kernel. We used the size of the clusters to infer the effective reproduction number, R<inf>t</inf>, and the rate of zoonotic spillover of MPXV into the human population. Out of 1,463 confirmed mpox cases reported in Tshuapa Province between 2013 and 2017, 878 had both date of symptom onset and a location with geographic coordinates. Results include an estimated R<inf>t</inf> of 0.82 (95% CI: 0.79 - 0.85) and a rate of 132 (95% CI: 122 - 143) spillovers per year assuming a reporting rate of 0.25. This estimate of R<inf>t</inf> is larger compared to most previous estimates. One potential explanation for this result is that R<inf>t</inf> could have increased in DRC over time due to declining population-level immunity conferred by smallpox vaccination, which was discontinued around 1982. R<inf>t</inf> could be overestimated if our assumption of one spillover event per cluster does not hold. Our results are consistent with increased transmissibility of MPXV in Tshuapa Province. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of Monkeypox virus (MPXV) among nine 2021 and 2022 U.S. monkeypox cases. A 2021 case was highly similar to the 2022 MPXV outbreak variant, suggesting a common ancestor. Analysis of mutations among these two lineages revealed an extreme preference for GA-to-AA mutations indicative of APOBEC3 cytosine deaminase activity that was shared among West African MPXV since 2017 but absent from Congo Basin lineages. Poxviruses are not thought to be subject to APOBEC3 editing; however, these findings suggest APOBEC3 activity has been recurrent and dominant in recent West African MPXV evolution. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Genomic surveillance of monkeypox virus (MPXV) during the 2022 outbreak has been mainly focused on single nucleotide polymorphism (SNP) changes. DNA viruses, including MPXV, have a lower SNP mutation rate than RNA viruses due to higher fidelity replication machinery. We identified a large genomic rearrangement in a MPXV sequence from a 2022 case in the state of Minnesota (MN), USA, from an abnormal, uneven MPXV read mapping coverage profile in whole-genome sequencing (WGS) data. We further screened WGS data of 206 U.S. MPXV samples and found seven (3.4 percent) sequenced genomes contained similar abnormal read coverage profiles that suggested putative large deletions or genomic rearrangements. Here, we present three MPXV genomes containing deletions ranging from 2.3 to 15 kb and four genomes containing more complex rearrangements. Five genomic changes were each only seen in one sample, but two sequences from linked cases shared an identical 2.3 kb deletion in the 3' terminal region. All samples were positive using VAC1 and Clade II (formerly West African)-specific MPXV diagnostic tests; however, large deletions and genomic rearrangements like the ones reported here have the potential to result in viruses in which the target of a PCR diagnostic test is deleted. The emergence of genomic rearrangements during the outbreak may have public health implications and highlight the importance of continued genomic surveillance. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

During April 17–May 5, 2023, 13 monkeypox (mpox) cases were reported to the Chicago Department of Public Health (CDPH) after 2 months during which only a single case had been reported. The cluster was remarkable because it comprised more than 10 cases at a time when sporadic cases or small clusters (i.e., involving fewer than three cases) were being reported in the United States, and >69% of the persons in this cluster had received 2 doses of JYNNEOS or 1 dose of ACAM2000 vaccine.* Some cases among persons who received doses of JYNNEOS vaccine are expected to occur based on vaccine effectiveness data (1,2); however, the observed proportion of cases among persons who had received 2 doses of JYNNEOS or 1 dose of ACAM2000 in this cluster was unusual. This increase in cases before large summer events scheduled nationwide and in Chicago raised concerns about possible future case increases. | | On May 9, 2023, CDPH issued a health alert,† urging clinicians to remain vigilant for mpox cases and encouraging vaccination for persons at risk for mpox.§ CDPH and CDC launched an investigation to 1) determine the cluster’s scope and etiology by evaluating patients’ commonalities, JYNNEOS¶ vaccine cold-chain management, whole genome sequencing of clinical samples, and serologic immune response after infections, and to 2) identify important risk factors for mpox exposure to guide prevention efforts. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.**

During May 17–December 31, 2022, 125 probable or confirmed U.S. monkeypox (mpox)† cases were reported among patients aged <18 years, including 45 (36%) in children aged ≤12 years. Eighty-three cases in persons aged <18 years diagnosed during May 17–September 24, 2022 were previously described (1); 28 (34%) of these were in children aged ≤12 years, 29% of whom did not have reported information on exposure. Among 20 (71%) of 28 patients with documented information on exposure, most were exposed by a household contact. This report updates the previous report using data collected during September 25–December 31, 2022, proposes possible mpox exposure routes in children aged ≤12 years, and describes three U.S. mpox cases in neonates. Household members or caregivers with mpox, including pregnant women and their health care providers, should be informed of the risk of transmission to persons aged <18 years, and strategies to protect persons aged <18 years at risk for exposure, including isolating household contacts with mpox, should be implemented immediately. | | During September 25–December 31, 2022, 17 children aged ≤12 years with probable or confirmed mpox were identified through national surveillance. CDC provided a questionnaire to state and local health departments for collection of the child’s history of exposure to any person with mpox§ during the previous 3 weeks, exposure settings, types of contact (e.g., skin-to-skin, being held or cuddled, diaper change, or toilet use), and precautions taken by the person with mpox (e.g., practiced isolation or covered lesions). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.¶

Monkeypox (mpox) is a serious viral zoonosis endemic in west and central Africa. An unprecedented global outbreak was first detected in May 2022. CDC activated its emergency outbreak response on May 23, 2022, and the outbreak was declared a Public Health Emergency of International Concern on July 23, 2022, by the World Health Organization (WHO),* and a U.S. Public Health Emergency on August 4, 2022, by the U.S. Department of Health and Human Services.(†) A U.S. government response was initiated, and CDC coordinated activities with the White House, the U.S. Department of Health and Human Services, and many other federal, state, and local partners. CDC quickly adapted surveillance systems, diagnostic tests, vaccines, therapeutics, grants, and communication systems originally developed for U.S. smallpox preparedness and other infectious diseases to fit the unique needs of the outbreak. In 1 year, more than 30,000 U.S. mpox cases were reported, more than 140,000 specimens were tested, >1.2 million doses of vaccine were administered, and more than 6,900 patients were treated with tecovirimat, an antiviral medication with activity against orthopoxviruses such as Variola virus and Monkeypox virus. Non-Hispanic Black (Black) and Hispanic or Latino (Hispanic) persons represented 33% and 31% of mpox cases, respectively; 87% of 42 fatal cases occurred in Black persons. Sexual contact among gay, bisexual, and other men who have sex with men (MSM) was rapidly identified as the primary risk for infection, resulting in profound changes in our scientific understanding of mpox clinical presentation, pathogenesis, and transmission dynamics. This report provides an overview of the first year of the response to the U.S. mpox outbreak by CDC, reviews lessons learned to improve response and future readiness, and previews continued mpox response and prevention activities as local viral transmission continues in multiple U.S. jurisdictions (Figure).

As of March 7, 2023, a total of 30,235 confirmed and probable monkeypox (mpox) cases were reported in the United States,(†) predominantly among cisgender men(§) who reported recent sexual contact with another man (1). Although most mpox cases during the current outbreak have been self-limited, cases of severe illness and death have been reported (2-4). During May 10, 2022-March 7, 2023, 38 deaths among persons with probable or confirmed mpox(¶) (1.3 per 1,000 mpox cases) were reported to CDC and classified as mpox-associated (i.e., mpox was listed as a contributing or causal factor). Among the 38 mpox-associated deaths, 94.7% occurred in cisgender men (median age = 34 years); 86.8% occurred in non-Hispanic Black or African American (Black) persons. The median interval from symptom onset to death was 68 days (IQR = 50-86 days). Among 33 decedents with available information, 93.9% were immunocompromised because of HIV. Public health actions to prevent mpox deaths include integrated testing, diagnosis, and early treatment for mpox and HIV, and ensuring equitable access to both mpox and HIV prevention and treatment, such as antiretroviral therapy (ART) (5).

The relative contribution of the respiratory route to transmission of mpox (formerly known as monkeypox) is unclear. We review the evidence for respiratory transmission of monkeypox virus (MPXV), examining key works from animal models, human outbreaks and case reports, and environmental studies. Laboratory experiments have initiated MPXV infection in animals via respiratory routes. Some animal-to-animal respiratory transmission has been shown in controlled studies, and environmental sampling studies have detected airborne MPXV. Reports from real-life outbreaks demonstrate that transmission is associated with close contact, and although it is difficult to infer the route of MPXV acquisition in individual case reports, so far respiratory transmission has not been specifically implicated. Based on the available evidence, the likelihood of human-to-human MPXV respiratory transmission appears to be low; however, studies should continue to assess this possibility.

Monkeypox (mpox) is a zoonotic disease caused by Monkeypox virus (MPXV), an Orthopoxvirus; the wild mammalian reservoir species is not known. There are two genetic clades of MPXV: clade I and clade II (historically found in central and west Africa, respectively), with only Cameroon reporting both clades (1). Human cases have historically been reported from 1) mostly rural, forested areas in some central and west African countries; 2) countries reporting cases related to population migration or travel of infected persons; and 3) exposure to imported infected mammals (2). The annual number of cases in Africa has risen since 2014 and cumulatively surpassed reports from the previous 40 years for most countries. This reemergence of mpox might be due to a combination of environmental and ecological changes, animal or human movement, the cessation of routine smallpox vaccination since its eradication in 1980, improvements in disease detection and diagnosis, and genetic changes in the virus (2). This report describes the epidemiology of mpox since 1970 and during 2018-2021, using data from national surveillance programs, World Health Organization (WHO) bulletins, and case reports, and addresses current diagnostic and treatment challenges in countries with endemic disease. During 2018-2021, human cases were recognized and confirmed in six African countries, with most detected in the Democratic Republic of the Congo (DRC) and Nigeria. The reemergence and increase in cases resulted in its being listed in 2019 as a priority disease for immediate and routine reporting through the Integrated Disease Surveillance and Response strategy in the WHO African region.* In eight instances, patients with mpox were identified in four countries outside of Africa after travel from Nigeria. Since 2018, introductory and intermediate training courses on prevention and control of mpox for public health and health care providers have been available online at OpenWHO.(†)(,)(§) The global outbreak that began in May 2022(¶) has further highlighted the need for improvements in laboratory-based surveillance and access to treatments and vaccines to prevent and contain the infection, including in areas of Africa with endemic mpox.

In July 2021, we conducted environmental sampling at the residence of a person in Dallas, Texas, USA, who had travel-associated human West African monkeypox virus (MPXV-WA). Targeted environmental swab sampling was conducted 15 days after the person who had monkeypox left the household. Results indicate extensive MPXV-WA DNA contamination, and viable virus from 7 samples was successfully isolated in cell culture. There was no statistical difference (p = 0.94) between MPXV-WA PCR positivity of porous (9/10, 90%) vs. nonporous (19/21, 90.5%) surfaces, but there was a significant difference (p<0.01) between viable virus detected in cultures of porous (6/10, 60%) vs. nonporous (1/21, 5%) surfaces. These findings indicate that porous surfaces (e.g., bedding, clothing) may pose more of a MPXV exposure risk than nonporous surfaces (e.g., metal, plastic). Viable MPXV was detected on household surfaces after at least 15 days. However, low titers (<10(2) PFU) indicate a limited potential for indirect transmission.

While mpox is rare among children in the United States, pediatric cases are being reported during the 2022 multinational mpox outbreak. Vaccines and antiviral medications developed for other orthopoxviruses have recently become widely used to prevent and treat mpox in both children and adults in the United States. Although scientific literature regarding mpox in children and adolescents is scant, prior case reports can provide valuable information about the clinical features and potential complications of untreated clade II mpox in these age groups. In this review, we summarize the epidemiology and clinical features of mpox in children and adolescents and provide recommendations for clinicians regarding its diagnosis, management, and prevention. Robust, dedicated surveillance of pediatric exposures and cases in the current outbreak, including the use of vaccines and therapeutics, are needed to guide clinical management and public health strategies.

Data on monkeypox in children and adolescents aged <18 years are limited (1,2). During May 17-September 24, 2022, a total of 25,038 monkeypox cases were reported in the United States,(dagger) primarily among adult gay, bisexual, and other men who have sex with men (3). During this period, CDC and U.S. jurisdictional health departments identified Monkeypox virus (MPXV) infections in 83 persons aged <18 years, accounting for 0.3% of reported cases. Among 28 children aged 0-12 years with monkeypox, 64% were boys, and most had direct skin-to-skin contact with an adult with monkeypox who was caring for the child in a household setting. Among 55 adolescents aged 13-17 years, most were male (89%), and male-to-male sexual contact was the most common presumed exposure route (66%). Most children and adolescents with monkeypox were non-Hispanic Black or African American (Black) (47%) or Hispanic or Latino (Hispanic) (35%). Most (89%) were not hospitalized, none received intensive care unit (ICU)-level care, and none died. Monkeypox in children and adolescents remains rare in the United States. Ensuring equitable access to monkeypox vaccination, testing, and treatment is a critical public health priority. Vaccination for adolescents with risk factors and provision of prevention information for persons with monkeypox caring for children might prevent additional infections.

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.(§) Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox(¶) during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy(††) in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.(§§) Engaging all persons with HIV in sustained care remains a critical public health priority.

The current worldwide monkepox outbreak has reaffirmed the continued threat monkeypox virus (MPXV) poses to public health. JYNNEOS, a Modified Vaccinia Ankara (MVA)-based live, non-replicating vaccine, was recently approved for monkeypox prevention for adults at high risk of MPXV infection in the United States. Although the safety and immunogenicity of JYNNEOS have been examined previously, the clinical cohorts studied largely derive from regions where MPXV does not typically circulate. In this study, we assess the quality and longevity of serological responses to two doses of JYNNEOS vaccine in a large cohort of healthcare workers from the Democratic Republic of Congo (DRC). We show that JYNNEOS elicits a strong orthopoxvirus (OPXV)-specific antibody response in participants that peaks around day 42, or 2 weeks after the second vaccine dose. Participants with no prior history of smallpox vaccination or exposure have lower baseline antibody levels, but experience a similar fold-rise in antibody titers by day 42 as those with a prior history of vaccination. Both previously naïve and vaccinated participants generate vaccinia virus and MPXV-neutralizing antibody in response to JYNNEOS vaccination. Finally, even though total OPXV-specific IgG titers and neutralizing antibody titers declined from their peak and returned close to baseline levels by the 2-year mark, most participants remain IgG seropositive at the 2-year timepoint. Taken together, our data demonstrates that JYNNEOS vaccination triggers potent OPXV neutralizing antibody responses in a cohort of healthcare workers in DRC, a monkeypox-endemic region. MPXV vaccination with JYNNEOS may help ameliorate the disease and economic burden associated with monkeypox and combat potential outbreaks in areas with active virus circulation.

As of October 11, 2022, a total of 26,577 monkeypox cases had been reported in the United States.* Although most cases of monkeypox are self-limited, lesions that involve anatomically vulnerable sites can cause complications. Ocular monkeypox can occur when Monkeypox virus (MPXV) is introduced into the eye (e.g., from autoinoculation), potentially causing conjunctivitis, blepharitis, keratitis, and loss of vision (1). This report describes five patients who acquired ocular monkeypox during July-September 2022. All patients received treatment with tecovirimat (Tpoxx)(†); four also received topical trifluridine (Viroptic).(§) Two patients had HIV-associated immunocompromise and experienced delays between clinical presentation with monkeypox and initiation of monkeypox-directed treatment. Four patients were hospitalized, and one experienced marked vision impairment. To decrease the risk for autoinoculation, persons with monkeypox should be advised to practice hand hygiene and to avoid touching their eyes, which includes refraining from using contact lenses (2). Health care providers and public health practitioners should be aware that ocular monkeypox, although rare, is a sight-threatening condition. Patients with signs and symptoms compatible with ocular monkeypox should be considered for urgent ophthalmologic evaluation and initiation of monkeypox-directed treatment. Public health officials should be promptly notified of cases of ocular monkeypox. Increased clinician awareness of ocular monkeypox and of approaches to prevention, diagnosis, and treatment might reduce associated morbidity.

Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of monkeypox virus (MPXV) among two 2021 and seven 2022 U.S. monkeypox cases: the major 2022 outbreak variant, B.1, and a minor contemporaneously sampled variant called A.2. Analyses of mutations among these two variants revealed an extreme preference for GA-to-AA mutations indicative of human APOBEC3 cytosine deaminase activity among Clade IIb MPXV (previously West African, Nigeria) sampled since 2017. Such mutations were not enriched within other MPXV clades. These findings suggest that APOBEC3 editing may be a recurrent and a dominant driver of MPXV evolution within the current outbreak.

Since May 2022, approximately 20,000 cases of monkeypox have been identified in the United States, part of a global outbreak occurring in approximately 90 countries and currently affecting primarily gay, bisexual, and other men who have sex with men (MSM) (1). Monkeypox virus (MPXV) spreads from person to person through close, prolonged contact; a small number of cases have occurred in populations who are not MSM (e.g., women and children), and testing is recommended for persons who meet the suspected case definition* (1). CDC previously developed five real-time polymerase chain reaction (PCR) assays for detection of orthopoxviruses from lesion specimens (2,3). CDC was granted 510(k) clearance for the nonvariola-orthopoxvirus (NVO)-specific PCR assay by the Food and Drug Administration. This assay was implemented within the Laboratory Response Network (LRN) in the early 2000s and became critical for early detection of MPXV and implementation of public health action in previous travel-associated cases as well as during the current outbreak (4-7). PCR assays (NVO and other Orthopoxvirus laboratory developed tests [LDT]) represent the primary tool for monkeypox diagnosis. These tests are highly sensitive, and cross-contamination from other MPXV specimens being processed, tested, or both alongside negative specimens can occasionally lead to false-positive results. This report describes three patients who had atypical rashes and no epidemiologic link to a monkeypox case or known risk factors; these persons received diagnoses of monkeypox based on late cycle threshold (Ct) values ≥34, which were false-positive test results. The initial diagnoses were followed by administration of antiviral treatment (i.e., tecovirimat) and JYNNEOS vaccine postexposure prophylaxis (PEP) to patients' close contacts. After receiving subsequent testing, none of the three patients was confirmed to have monkeypox. Knowledge gained from these and other cases resulted in changes to CDC guidance. When testing for monkeypox in specimens from patients without an epidemiologic link or risk factors or who do not meet clinical criteria (or where these are unknown), laboratory scientists should reextract and retest specimens with late Ct values (based on this report, Ct ≥34 is recommended) (8). CDC can be consulted for complex cases including those that appear atypical or questionable cases and can perform additional viral species- and clade-specific PCR testing and antiorthopoxvirus serologic testing.

In May 2022, the Salt Lake County Health Department reported two real-time polymerase chain reaction (PCR)-confirmed travel-associated cases of monkeypox to the Utah Department of Health and Human Services (UDHHS). The two persons with monkeypox (patients A and B) lived together without other housemates. Both persons experienced prodromal symptoms (e.g., fatigue and body aches). Eight days after symptom onset, patient A experienced penile lesions; lesions spread to the lips, hands, legs, chest, and scalp by day 10. Patient B experienced prodromal symptoms 8 days after illness onset of patient A; patient B experienced a lesion on the foot which spread to the leg and finger by day 11. Although both patients had lesions in multiple anatomic areas, the overall number of lesions was small, and lesions varied in presentation from "pimple-like" or ulcerated, to characteristically well-circumscribed and centrally umbilicated. Both patients had mild illness. The time from symptom onset to resolution was approximately 30 days for patient A and approximately 22 days for patient B.