Consuelo Silva Oliveira

The Oropouche virus (OROV) is an arbovirus (Peribunyaviridae: Orthobunyavirus) that traditionally causes febrile outbreaks in Latin America’s Amazon region. Previously, OROV was not associated with severe pregnancy outcomes. During the 2022–2024 outbreak in Brazil, OROV expanded geographically, revealing links to adverse pregnancy outcomes. This study describes six cases with varied fetal outcomes, including miscarriage, antepartum, intrauterine fetal demise (IFD), and normal development, correlating with maternal symptoms but not symptom severity. Vertical transmission was confirmed by detecting OROV through RT-qPCR, ELISA, and immunohistochemistry in fetal tissues. Genome sequencing from an IFD case identified a novel reassortment pattern reported in the 2022–2024 outbreak. Severe encephalomalacia, meningoencephalitis, vascular compromise, and multi-organ damage were evident, underscoring the significant risk OROV poses to fetal development and emphasizing the need for further investigation.

Oropouche fever is caused by the Oropouche virus (OROV; Bunyaviridae, Orthobunyavirus), one of the most frequent arboviruses that infect humans in the Brazilian Amazon. This year, an OROV outbreak was identified in Brazil, and its vertical transmission was reported, which was associated with fetal death and microcephaly. We describe the clinical manifestations identified in three cases of congenital OROV infection with confirmed serology (OROV-IgM) in the mother-newborn binomial. One of the newborns died, and post-mortem molecular analysis using real-time RT-qPCR identified the OROV genome in several tissues. All three newborns were born in the Amazon region in Brazil, and the mothers reported fever, rash, headache, myalgia, and/or retro-orbital pain during pregnancy. The newborns presented with severe microcephaly secondary to brain damage and arthrogryposis, suggestive of an embryo/fetal disruptive process at birth. Brain and spinal images identified overlapping sutures, cerebral atrophy, brain cysts, thinning of the spinal cord, corpus callosum, and posterior fossa abnormalities. Fundoscopic findings included macular chorioretinal scars, focal pigment mottling, and vascular attenuation. The clinical presentation of vertical OROV infection resembled congenital Zika syndrome to some extent but presents some distinctive features on brain imaging and in several aspects of its neurological presentation. A recognizable syndrome with severe brain damage, neurological alterations, arthrogryposis, and fundoscopic abnormalities can be associated with in utero OROV infection.

Oropouche fever is caused by the Oropouche virus (OROV; Bunyaviridae, Orthobunyavirus), one of the most frequent arboviruses that infect humans in the Brazilian Amazon. This year, an OROV outbreak was identified in Brazil, and its vertical transmission was reported, which was associated with fetal death and microcephaly. We describe the clinical manifestations identified in three cases of congenital OROV infection with confirmed serology (OROV-IgM) in the mother-newborn binomial. One of the newborns died, and post-mortem molecular analysis using real-time RT-qPCR identified the OROV genome in several tissues. All three newborns were born in the Amazon region in Brazil, and the mothers reported fever, rash, headache, myalgia, and/or retroorbital pain during pregnancy. The newborns presented with severe microcephaly secondary to brain damage and arthrogryposis, suggestive of an embryo/fetal disruptive process at birth. Brain and spinal images identified overlapping sutures, cerebral atrophy, brain cysts, thinning of the spinal cord, corpus callosum, and posterior fossa abnormalities. Fundoscopic findings included macular chorioretinal scars, focal pigment mottling, and vascular attenuation. The clinical presentation of vertical OROV infection resembled congenital Zika syndrome to some extent but presents some distinctive features on brain imaging and in several aspects of its neurological presentation. A recognizable syndrome with severe brain damage, neurological alterations, arthrogryposis, and fundoscopic abnormalities can be associated with in-utero OROV infection.

Despite great advances in our knowledge of the consequences of Zika virus to human health, many questions remain unanswered, and results are often inconsistent. The small sample size of individual studies has limited inference about the spectrum of congenital Zika manifestations and the prognosis of affected children. The Brazilian Zika Cohorts Consortium addresses these limitations by bringing together and harmonizing epidemiological data from a series of prospective cohort studies of pregnant women with rash and of children with microcephaly and/or other manifestations of congenital Zika. The objective is to estimate the absolute risk of congenital Zika manifestations and to characterize the full spectrum and natural history of the manifestations of congenital Zika in children with and without microcephaly. This protocol describes the assembly of the Consortium and protocol for the Individual Participant Data Meta-analyses (IPD Meta-analyses). The findings will address knowledge gaps and inform public policies related to Zika virus. The large harmonized dataset and joint analyses will facilitate more precise estimates of the absolute risk of congenital Zika manifestations among Zika virus-infected pregnancies and more complete descriptions of its full spectrum, including rare manifestations. It will enable sensitivity analyses using different definitions of exposure and outcomes, and the investigation of the sources of heterogeneity between studies and regions.

Introduction: The recent Zika virus(ZIKV) epidemic in Brazil was characterized by a range of different clinical presentations, particularly microcephaly, Guillain-Barré syndrome, and death. In this context, we determined the causal relationship between fatal microcephaly cases and ZIKV infection. Methods: Twelve fatal cases of neonates, whose mothers were infected with ZIKV during pregnancy, were examined; cases included nine neonatal deaths due to microcephaly, one miscarriage, and two stillbirths. Tissue samples were obtained from all cases at necropsy and were submitted for virological investigation (RT-qPCR and virus isolation) and/or histopathology (hematoxylin and eosin staining) and immunohistochemical assay for the detection of ZIKV antigens. Results: ZIKV antigens and/or ZIKV RNA were detected in tissue samples of all 12 cases examined. ZIKV was recovered in one case. Results of the virological and immunohistochemical analyses, as well as the anatomic abnormalities and histopathologic changes observed at necropsy on the 12 fatal cases, are presented. Conclusions: Data from these 12 cases provide strong evidence of the causal relationship between ZIKV and congenital disease in fetuses of women who were infected with the virus during pregnancy.