Three Cases of Vertical Transmission of Clade Ib Monkeypox Virus

To the Editor:

Mpox, caused by the monkeypox virus (MPXV), has been associated with adverse pregnancy outcomes, but evidence of vertical transmission remains limited.^1–3 Concerns of transplacental transmission are heightened by the ongoing Clade Ib mpox epidemic, which often affects individuals of reproductive age.⁴ We report three cases of Clade Ib MPXV infection in pregnant women, providing molecular and histopathological evidence of transplacental transmission across all trimesters. (Details of methodology, clinical presentation, and histopathology are in the supplementary appendix.)

The first case involved a woman at six weeks of gestation who developed fever, generalized rash, inguinal adenopathy, and genital edema and tested positive for Clade Ib MPXV. Despite symptomatic treatment, she experienced a spontaneous abortion. MPXV DNA was detected in embryonic and placental tissues, with Ct values of 13.4 and 20.1, respectively (Table). Histopathology of these tissues demonstrated MPXV antigen colocalized with CD68 positive placental villous macrophages (Hofbauer cells) and alpha-fetoprotein positive embryonic cells, indicating transplacental transmission (Figure S1A–K).

Table:

Clinical characteristics, virology and pregnancy outcomes in women infected with clade Ib MPXV

	Case 1	Case 2	Case 3
Clinical presentation
Age% (years)	20-30	25-35	20-30
Gestational age at diagnosis of infection (weeks)	6	16	34
HIV status	Unknown	Positive	Positive
Receiving ART	NA	Yes	No
Mode of transmission	Sexual contact	Sexual contact	Skin to skin contact
Symptoms	Fever, skin lesions generalized and genital, inguinal adenopathy, pruritus, genital pain, vaginal discharge, labial edema	Fever, skin lesions generalized and genital, inguinal adenopathy, genital pain	Fever, dysphagia, dehydration, hypotension, generalized skin lesions, ulcerative genital lesions, generalized pruritus
Number of lesions	100-250	> 250	> 250
WHO severity score*	Severe	Grave	Grave
Pregnancy outcome	Spontaneous abortion	IUFD	Live neonate with congenital mpox
MPXV-PCR results
Skin lesion mother	Pos (Ct 23.5)	NA	Pos (Ct 21.8)
Oro-pharyngeal swab mother	Pos (Ct 30.5)	Pos (Ct 38.6)	Pos (Ct 30.5)
Vaginal swab mother	NA	Pos (Ct 35.1)	NA
Blood mother	Pos (Ct 33.1)	Neg	NA
Breast milk	NA	Pos (Ct 39)	Neg
Placenta swab	Pos (Ct 20.1)	Pos (Ct 19.3)	Pos (Ct 23.7)
Swab of fetal or embryonic products or live newborn	Pos (Ct 13.4)	Pos (Ct 18.3)	Pos (Ct 38.2)
MPXV Clade identification	Ib	Ib	Ib

Abbreviations: IUFD denotes intra-uterine fetal demise, Pos denotes MPXV DNA detected, Neg denotes MPXV not detected, Ct denotes Cycle Threshold Value, ART denotes antiretroviral therapy, NA denotes ‘not available’ or ‘not applicable’.

^%Age ranges are provided to avoid patient identification.

^*WHO severity score based on number of lesions: mild (< 25 lesions); moderate (25-99 lesions); severe (100-250 lesions), grave (> 250 lesions).

The second case involved an HIV-positive woman at 16 weeks of gestation who presented with widespread vesiculopustular lesions, fever, and dysphagia. Fifteen days after she tested positive for Clade Ib MPXV, fetal movements ceased, and ultrasound confirmed intrauterine fetal demise. A cesarean delivery was performed after unsuccessful labor induction; the fetus had several mpox-like lesions on the face, chest, abdomen, and upper limbs. MPXV DNA was detected in placental and fetal tissue, with Ct-values of 19.3 and 18.3, respectively (Table).

The third case involved an HIV-positive woman at 34 weeks of gestation with generalized mpox lesions, and genital ulcers, who tested positive for Clade Ib MPXV. She was admitted with hypotension but recovered and was discharged after 29 days. Thirteen days later, at 40 weeks gestation, she delivered a live infant with multiple ulcerative skin lesions (Figure S2); MPXV DNA was detected in placental swab (Ct 23.7) and oropharyngeal swab from the newborn (Ct 38.2). Histopathology revealed MPXV antigen within the placental villi, co-localized with CD68 positive-cells (Figure S1L–P). The mother reported the infant’s death three months later, likely unrelated to mpox.

These findings provide evidence that Clade Ib MPXV can be vertically transmitted, resulting in pregnancy loss or congenital infection, consistent with isolated previous reports on Clade Ia MPXV.^1,2 These findings support the need for preventive interventions in pregnant women, including vaccination. Prospective large scale studies are required to better understand perinatal outcomes associated with mpox in pregnancy and to guide clinical management.