A Case of Neonatal Monkeypox Treated With Oral Tecovirimat Free

The patient is a 10-day old, full-term female who presented to the emergency department of a secondary hospital in the southeastern region of the United States with fever and generalized rash. Birth history was significant for a maternal history of herpes simplex virus type 2 (HSV-2) that had been treated with antiviral medication for 10 days before delivery. The mother had no active herpetic lesions. The patient was delivered by cesarean delivery because of nonreassuring fetal heart tones. The patient breastfed since birth. Three days after delivery, the mother developed fever with subsequent appearance of multiple pustular and umbilicated lesions on her hands, feet, and trunk. On day 10 of life, our neonatal patient presented with fever and a generalized erythematous, papular, and pustular rash over her face, eyelids, head, hands, feet, trunk, and genitalia. She underwent febrile neonate workup including collection of blood, urine, and cerebrospinal fluid (CSF) cultures, and she was empirically treated with ampicillin, gentamicin, and acyclovir. Workup revealed leukocytosis (17.1 × 10⁹/L), normal C-reactive protein (CRP), normal procalcitonin, and normal electrolytes. CSF studies showed white blood cell count 6/mm³, red blood cell count 51/mm³, glucose 67 mg/dL, protein 42 mg/dL, and a negative FilmArray meningitis/encephalitis panel (which included HSV-1 and -2). She was transferred subsequently to a tertiary pediatric hospital for a higher level of care.

Because of a high suspicion of neonatal Mpox because of the similarity of neonatal and maternal rashes, the patient was placed on airborne isolation precautions in accordance with the Centers for Disease Control and Prevention recommendations. Swabs of various lesions were obtained on admission and sent for polymerase chain reaction (PCR) testing for Mpox along with HSV shell vial viral culture and PCR. The infectious disease service was consulted for further recommendations. The mother was counseled about the risks and benefits of breastfeeding and about the lack of evidence to guide treatment when mother and infant are simultaneously infected. Her mother decided to stop breastfeeding and opted for formula feeding since admission. After consultation with the Centers for Disease Control and Prevention, oral tecovirimat was started on day 3 of admission. Tecovirimat was administered at a dose of 50 mg every 12 hours. Capsules of 200 mg were opened and emptied into a dosing cup and 20 mL of water was added and uniformly mixed for 30 seconds. An oral syringe was then used to administer 5 mL of mixture.⁴  After medication administration, the patient was bottle-fed with standard infant formula. Ophthalmology was also consulted because of the presence of periorbital lesions. External, anterior segment, and dilated fundus examinations did not reveal ocular involvement, but moxifloxacin eye drops and ophthalmic erythromycin were prescribed based on ophthalmology recommendations to prevent secondary bacterial infection.

Because culture of blood, urine, and CSF tests were negative, empirical antimicrobial therapy was discontinued 72 hours after admission. PCR testing for Mpox performed on admission resulted inconclusive. Mpox PCR tests of 3 additional samples obtained from several different lesions were each positive. During this time, her mother was referred for Mpox testing, which was also positive. After clinical evaluation, the mother was not prescribed tecovirimat. Although fevers persisted during the first 4 days of her admission (maximum temperature of 38.7 °C), she remained clinically stable. Most cutaneous lesions evolved into larger pustules with a smaller erythematous base, whereas other lesions became umbilicated (Fig 1 and 2). CRP levels peaked on day 6 of admission (39.7 mg/L from 5 mg/L at presentation), white blood cell count decreased, and renal function remained stable. However, slight elevation of transaminases was detected on day 6 of admission, with aspartate transferase and alanine transferase levels of 90 and 65 U/L, respectively.

With remission of the fever, improvement of lesions, and adequate tecovirimat tolerability, the neonate was discharged after six days with instructions to complete a fourteen-day course of oral tecovirimat. Outpatient follow-up four days after discharge showed improvement but not complete resolution of lesions as well as reductions in aspartate transferase (74 U/L), alanine transferase (63 U/L), and CRP (18.6 mg/L).

Little information about neonatal mpox infection exists in the current literature, especially related to the recent epidemic. Historically, Mpox infection in children has been related to higher mortality and morbidity. In the period 1970 to 1999, fatalities were documented at 100%, which fell to 37.5% in the period 2000 to 2019.⁵  However, limited cases have been reported for this age group, and most reports are from low-income countries with poor access to diagnostic tools.⁶  In the current outbreak, few cases of neonatal Mpox have been reported. One published case described a 10-day old with perinatally acquired Mpox infection who presented with a similar exanthem to our patient’s but was coinfected with adenovirus, resulting in a critical illness requiring ventilatory support and intensive care services.³  Our patient’s clinical course differed radically because she presented with fevers and mucocutaneous disease without identified secondary infection or clinical instability.

Because children historically have been implicated in more severe disease, expedited initiation of treatment was essential. Prompt infectious disease consultation yielded early initiation of oral tecovirimat. Although there are no data available in humans about optimal timing of tecovirimat and prognosis, treatment is likely to be more effective when started early. In our patient, the likelihood of Mpox infection was high because maternal lesions that were highly suggestive of mpox, and empirical initiation of tecovirimat could have caused a quicker defervescence and an earlier discharge. Further research is necessary to determine the effect of early empirical therapy in high-risk patients who are suspected to be infected by Mpox.

We considered treatments other than oral tecovirimat for our patient. Intravenous tecovirimat was an option because she was at high risk for severe disease. However, the intravenous formulation is reserved for adults and children unable to take oral therapy or for whom there is a concern for intestinal malabsorption. Additionally, the bioavailability of oral tecovirimat is dependent on adequate intake of a full, fatty meal. Our patient maintained adequate oral intake during her disease course, so that an oral formulation was appropriate.⁴  Furthermore, cidofovir and brincidofovir have been shown to be effective against Mpox in animal models.⁷  However, no clinical data exist about efficacy against infection in humans, and their use can be associated with nephrotoxicity and neutropenia.⁸  Vaccinia immune globulin intravenous can be considered an additional treatment in patients with a severe infection in which the development of adequate antibody response may be impaired. However, vaccinia immune globulin intravenous has no proven benefit in the treatment of Mpox and it is unknown whether an infected person will benefit from it.^9,10  In our case, the patient had exclusive mucocutaneous diseases without any serious complications, so we did not prescribe additional treatments.

Although our patient’s course was complicated by mild transaminase elevation, the etiology of this remains uncertain. The patient had received oral tecovirimat for 3 days before evaluation of her hepatic function. Although transaminase elevation has not been described as a side effect of tecovirimat,¹¹  no safety studies have been conducted in children.¹²  Conversely, transaminase elevation has been described in approximately 50% of patients in small case series of adults with Mpox infection. These cases did not receive treatment with tecovirimat because it had not yet been used to treat Mpox.¹³  In our case, the elevation was detected on day 7 of signs (day 3 of treatment), and by day 10 (day 6 of treatment), the levels were declining.

Regarding the transmissibility, skin-to-skin contact is the most frequently described route.¹⁴  Although our patient most likely had been infected via skin-to-skin contact, we could not exclude vertical transmission based on the timeline of clinical signs. The incubation period of Mpox is known to be from 1 to 3 weeks,¹⁴  and the onset of maternal symptoms occurred 3 days after delivery with development of signs in our patient on day 8 of life. What suggests a postnatal transmission in our case is that vertical transmission has been documented early in pregnancy, with a large percentage of fetal demise. Furthermore, perinatally acquired Mpox is associated with serious adverse outcomes.^5,6  Although infected mothers are advised against breastfeeding to prevent transmission through close contact, it is unknown if Mpox is transmitted through breast milk.¹⁵  Additionally, there is no evidence to guide recommendations on breastfeeding when both mother and child are infected. Further research is needed to elucidate the transmissibility of Mpox through breastmilk.

Our case highlights the importance of early consideration of Mpox as an etiology of neonatal rash, especially in febrile neonates. Early subspecialty consultations can lead to prompt initiation of treatment. Our patient tolerated oral tecovirimat well, and this treatment may have prevented the development of more severe disease. The only possible side effect of tecovirimat was mild transient elevation of hepatic transaminases, which may have been due to the Mpox infection itself.

CRP

C-reactive protein

CSF

cerebrospinal fluid

HSV

herpes simplex virus

Mpox

monkeypox

PCR

polymerase chain reaction