Mpox in Children: 3 Cases Free

A previously healthy and fully immunized infant (age range 6–12 months) developed a scalp lesion ∼1 week after exposure to a household contact with confirmed mpox. The initial lesion was an umbilicated papule on the scalp, which then enlarged and ulcerated. The infant was presumed to be exposed via skin-to-skin contact with a direct caregiver known to have infection with mpox. Viral swabs of the infant’s lesion were obtained by the patient’s primary care physician in the outpatient setting and the diagnosis of mpox was confirmed 3 days after the lesion first appeared. Although initially well-appearing, the infant became febrile and irritable, and new lesions involving the lips, neck, limbs, and torso developed over the following week, with a total of 15 lesions noted. The original scalp lesion became large, erythematous, and indurated, suggesting bacterial superinfection. Fever was attributed to the superinfection rather than to mpox. The infant was seen in the outpatient infectious disease clinic 7 days after the initial lesion appeared, and because of the patient’s young age, the decision was made to initiate therapy with oral tecovirimat, as well as oral trimethoprim-sulfamethoxazole for bacterial superinfection. The family was advised to administer the tecovirimat with bottle feeding to comply with the recommendation to administer this medication with a fatty meal. Although CDC guidance recommends early initiation of therapy for eligible individuals, treatment was delayed until this time because of parental hesitancy. No new lesions appeared after starting tecovirimat and all lesions crusted over by day 7 of treatment (Fig 1A). The infant completed a 14-day course of tecovirimat, using weight-based dosing per CDC EA-IND guidance. Lesions had fully healed by the end of therapy. The patient’s mother and siblings received postexposure prophylaxis with the Bavarian-Nordic-strain Modified Vaccinia Ankara vaccine (MVA-BN) within several days of our patient’s presentation; of note, these family members had also been exposed to the index case. The patient’s siblings remained healthy; however, the patient’s mother did go on to develop mpox infection, likely because of prolonged exposure before receipt of vaccination. It was suspected that the mother’s infection was acquired from direct contact with the child, because her infection began with an initial lesion on her palm, and the timing of infection was more consistent with transmission from the child, rather than from the index case.

A young female child (age range 2–7 years), fully immunized with standard childhood vaccines, with a history of intermittent asthma and mild eczema, presented to the emergency department (ED) with a 2-week history of a progressive facial lesion. She had a single day of fever 13 days before presentation, followed by development of a small bump on the right side of her nose. Over the subsequent 2 weeks, the lesion progressively increased in size, umbilicated with central scabbing, and developed surrounding erythema (Fig 2A). She had recrudescence of fever on the day of presentation. Her examination was notable for an ∼0.5 cm umbilicated lesion with a dark center and surrounding erythema on the right side of her nose, as well as enlarged, tender right preauricular and cervical lymph nodes. Her family denied any known mpox exposures, though 1 family member developed “bumps on his arm” several days before our patient’s first ED visit (but after our patient developed her first lesion); the family member reportedly had 2 negative MPXV polymerase chain reactions (PCRs) from swabs of these lesions. A swab of the child’s facial lesion was sent for MPXV PCR. She was started on oral cephalexin for presumed cellulitis. During the 3 days after the visit, she developed conjunctival injection and mild discharge from her right eye and similar new lesions on her philtrum, eyebrow, neck, and hand (Fig 2B–E). The original lesion on her nose had also increased in size and had become darker in the center with surrounding ecchymosis (Fig 2B). Three days after the ED visit, the MPXV PCR test reported detectable MPXV DNA (Fig 1B).

This patient was recalled to the ED. Repeat MPXV PCR testing was positive. On the recommendation of ophthalmology, she was prescribed a 7-day course of trifluridine ophthalmic drops for possible ocular involvement. The following day, she began treatment with oral tecovirimat per CDC EA-IND guidance. By day 3 of treatment, all lesions had begun to dry or crust and ocular symptoms had resolved; by day 8 of treatment, all lesions had fully crusted or healed. She completed a 14-day course, with all care provided as an outpatient; she experienced no adverse effects of medication. Household contacts were advised to seek postexposure prophylaxis with immunization.

A previously healthy and fully immunized adolescent female (age range 14–17 years) presented with several days of papular vaginal lesions, nonspecific genital pain, and vaginal discharge, for which she had sought medical care multiple times over the preceding days and had commenced treatment of presumed herpes simplex virus infection. She had no fever and no known confirmed mpox exposure. She reported that she was sexually active with 1 male sexual partner; she reported that this partner had developed genital lesions >1 week before onset of her symptoms and that his lesions had since resolved. He had reportedly been tested for sexually transmitted infections at a sexual health clinic, but it is not known whether he was tested for mpox. Further social history regarding the sexual partner was not provided.

On examination, the patient had several papules over her upper extremities, torso, and lower extremities, some of which were umbilicated. She was admitted to the hospital for exam under anesthesia (because of severe pain and intolerance of exam otherwise), and pain control with nonsteroidal antiinflammatory drugs and opioids. Testing was sent for herpes simplex virus, chlamydia, gonorrhea, syphilis, HIV, and mpox. Of note, she also had negative urine β human chorionic gonadotropin testing. Ceftriaxone was started empirically for possible sexually transmitted coinfections and bacterial superinfection while studies were pending. Testing resulted positive only for MPXV detected by PCR from swab of the lesions. Because of significant pain and the anatomic location of lesions, oral tecovirimat was started on the day mpox testing resulted positive (Fig 1C). She was treated with tecovirimat for 14 days. By day 3 of treatment, her pain had improved, her lesions were crusting, and she was discharged from the hospital. Her pain resolved completely and lesions healed fully by day 7 of treatment. No other household members or other contacts developed lesions.

The described cases highlight distinct routes of transmission: Household contact, unidentified exposure, and sexual contact. Household transmission is the most common mode of transmission in young children; this occurs mainly via close contact such as direct skin-to-skin contact in the context of caregiving, which likely was responsible for our first case (the infant exposed to a direct caregiver with confirmed mpox). For adolescents and adults, transmission via skin-to-skin contact can also occur in the context of sexual activity.¹²  Additionally, viable MPXV has been found on fomites, particularly porous fomites such as bedding, clothing, and towels which are often shared within a household, though this is thought to be a less common route of transmission.^13,14  Given that cases may occur in the context of skin-to-skin contact, providers should provide guidance regarding the need for isolation until lesions have resolved, including limiting attendance at day care or other child care centers. We offered treatment with tecovirimat when the patient presented with lesions because of the known exposure and high suspicion for mpox; however, therapy was delayed because of parental hesitancy. It is possible that this case could have been prevented by earlier presentation to care and administration of postexposure prophylaxis immunization.

In the case of the young child, her family reported no known exposures at the time of presentation. Although she had no obvious epidemiologic history to suggest mpox, an astute ED provider recognized the umbilicated lesion and, given ongoing community transmission, maintained a high index of suspicion for mpox. Though mpox was not felt to be the most likely diagnosis, testing was appropriately performed and ultimately resulted in a timely correct diagnosis. The progression of her lesions, with extension to involve the eye and hand, suggested autoinoculation and raised concern for the possibility of ocular mpox infection (although this was not confirmed). Providers should counsel patients and families regarding the need to maintain good hand hygiene. Particularly in young children or those with facial involvement, providers should monitor closely for ocular involvement, which may manifest as vision changes, redness, or eye pain. Ocular disease may rarely progress to more serious consequences such as ocular/corneal scarring and even vision loss.

Given the broad range of ages and developmental levels within pediatrics, it is important to recognize that transmission patterns and clinical presentations of adolescents may more closely mirror those seen in adults. The adolescent female patient we describe had undiagnosed mpox lesions for over a week despite seeking medical care multiple times. The absence of a confirmed exposure, her young age, and heterosexual sex practices likely contributed to the delay in diagnosis. Clinicians who care for adolescents should include mpox on the differential diagnosis for patients presenting with genital lesions, or with possible sexual exposures. In cases where mpox is acquired via sexual transmission, providers should maintain a high index of suspicion for other sexually transmitted infections, including HIV, because there has been a reported association between HIV and mpox diagnosis.¹² 

It is notable that 2 of the described patients did not present with the classic prodrome of fever, malaise, myalgia, or lymphadenopathy. Mpox has historically presented with more robust lymphadenopathy in comparison with smallpox⁷ ; however, many adults with mpox during the 2022 outbreak presented without a prodrome, including a lack of lymphadenopathy. In our 2 cases with known modes of transmission, the patients developed lesions soon after exposure, likely at the site of inoculation, which quickly progressed to involve multiple body sites. These cases followed the classic progression of lesions, which typically progress over a period of 2-to-3 weeks, from macules to papules, then pustules with umbilication before crusting and finally healing.⁸  However, in the 2022 outbreak, it was observed that many patients present with only a single lesion in the genital region, which may then spread to other body sites,⁸  or may present with a rash consisting of lesions at different stages even in the same anatomic location, in contrast to classic descriptions of all lesions progressing uniformly.

It should be noted that mpox cases among children and adolescents in the United States occurred disproportionately among Hispanic and Black children, highlighting disparities in health care and the need to ensure equitable and timely access.¹² 

Testing for Orthopoxvirus or MPXV DNA should be performed by vigorously swabbing the surface of lesions using a synthetic swab.⁹  Because of the possibility of false positive results, it is advised that testing should be performed only with high suspicion of mpox infection, either because of epidemiologic risk factors (such as known exposure) or clinical presentation with prodrome and/or typical rash/lesions.^15,16  Providers should consider retesting in cases of suspected false positive results.

Supportive care is the mainstay of mpox treatment. However, for patients who present with or who are at risk for severe disease (eg, immunocompromised individuals or children, especially those aged <1 year), as well as those at risk for complications from infection involving sensitive anatomic areas (eg, eyes), antiviral therapy should be considered. Tecovirimat, a novel antiviral that targets a viral envelope protein (VP37) specific to Orthopoxviruses, is US Food and Drug Administration (FDA) approved for the treatment of smallpox via the animal rule.¹⁷  Given this method of approval, there are limited safety data and no human clinical trial data for this drug. Tecovirimat is currently available only through a CDC-held EA-IND; however, clinical trials are ongoing. This drug appears to be well tolerated, with the most common side effects being headache and nausea.¹⁸  Currently, weight-based dosing recommendations for children in the EA-IND are based on pharmacokinetic simulations, and no formal safety data have been obtained.¹⁹  In our cases, tecovirimat was prescribed per these CDC guidelines, was well tolerated by all 3 children including 1 infant. Although all showed clinical improvement, it is unclear to what degree tecovirimat contributed to disease resolution, given that the drug was prescribed relatively late in the illness course for all 3 cases. There are ongoing studies to evaluate its efficacy and impact.²⁰ 

Additional medical countermeasures that may have activity against Orthopoxviruses are reserved for more severe cases. These include vaccinia immunoglobulin, as well as cidofovir and brincidofovir, which is also available only via an FDA-held EA-IND.

Currently, 2 live vaccinia vaccines are available for mpox prevention and postexposure prophylaxis. ACAM2000 is a live vaccinia virus vaccine; however, because it is replication-competent, it is not indicated for individuals aged <12 months, nor for those who are immunocompromised. Given that live virus is detectable at the site of the inoculation and can be transmitted via direct contact, its use has been avoided during the 2022 mpox outbreak. The MVA-BN is a live virus vaccine based on an attenuated nonreplicating Orthopoxvirus strain and has been widely used as a vaccine for mpox during this outbreak. An emergency use authorization expanded the availability of MVA-BN to pediatric patients aged <18 years. The CDC recommends vaccination for both preexposure prophylaxis, as well as postexposure prophylaxis (PEP); eligible persons include anyone who has multiple sex partners or known mpox exposure within the last 14 days.²¹  The vaccine should be offered to patients as soon as possible after known exposure, but may be effective when administered up to 14 days after exposure. In several of the cases we described, patients’ family members (including parents and siblings) received postexposure prophylaxis vaccinations; however, in at least 1 case, a parent went on to develop infection, likely because of prolonged exposure before vaccination. Prevention efforts for adolescents at risk for acquiring mpox (particularly those who identify as men who have sex with men), as well as children and families, should include education around signs and symptoms of disease and routes of transmission, as well as promotion of vaccines for preexposure prophylaxis.

We described the first 3 reported cases of mpox in children aged <18 in New York City; these cases exhibited variable routes of transmission, as well as variable clinical presentations and diagnostic challenges. Although cases in the United States have decreased, outbreaks continue to occur.²²  Particularly during times of ongoing community transmission, pediatric providers should maintain a high index of suspicion for mpox in children and adolescents, and consider testing patients who present with epidemiologic risk factors or with typical lesions (Table 1).

CDC

Centers for Disease Control and Prevention

ED

emergency department

FDA

US Food and Drug Administration

EA-IND

expanded access investigational new drug application

MPXV

monkeypox virus

MVA-BN

Bavarian-Nordic-strain Modified Vaccinia Ankara vaccine

PCR

polymerase chain reaction