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Five confirmed cases of vertical transmission of Oropouche virus — all fatal and showing a consistent pattern of central nervous system malformations — establish the pathogen as an obstetric concern that requires changes to prenatal protocols in areas where the virus is endemic, according to a review published in the Journal of Maternal-Fetal & Neonatal Medicine.
Conducted by researchers from several Brazilian institutions and one Italian institution, the study consolidates molecular, clinical, and epidemiologic evidence documenting detection of viral RNA in placenta, amniotic fluid, and fetal tissues including central nervous system tissue from pregnant women infected in the first trimester. The malformation pattern includes microcephaly, ventriculomegaly, corpus callosum dysgenesis, posterior fossa abnormalities, and arthrogryposis.
Based on these findings, the review recommends molecular testing for symptomatic pregnant women, serial ultrasonography with focused neurosonography, and mandatory reporting of all suspected or confirmed cases — measures that should be implemented immediately in prenatal services that serve regions with documented Oropouche circulation.
Vertical Transmission and Fetal Neurotropism
Molecular confirmation of vertical transmission was made by detecting viral RNA by reverse transcription polymerase chain reaction (RT-PCR) in multiple maternal-fetal samples: placental tissue, umbilical cord blood, amniotic fluid, and fetal organs, including brain tissue. In addition to the five confirmed cases identified in Pernambuco, Ceará and Acre (Pernambuco and Ceará are states in Brazil’s Northeast region; Acre is in the far-western Amazon region of Brazil) 22 other fetal deaths remain under investigation. All cases with documented malformations occurred after maternal infection in the first trimester, suggesting a critical window of vulnerability during fetal organogenesis.
The malformation pattern observed includes severe microcephaly, ventriculomegaly, cerebral atrophy, agenesis or dysgenesis of the corpus callosum, posterior fossa abnormalities (cerebellar hypoplasia and vermian anomalies), intracranial calcifications, arthrogryposis and ocular changes including microphthalmia and chorioretinal atrophy. The consistency of these findings across multiple cases suggests a recognizable clinical phenotype, although it is not yet fully characterized.
Placental histopathology showed necrotizing villitis, deciduitis, and a mononuclear inflammatory infiltrate, with evidence of viral replication in trophoblastic cells, supporting a hematogenous transplacental route as the main mechanism of fetal infection.
Timing and Laboratory Strategy
Molecular diagnosis should be performed between the second and seventh day after symptom onset, when viremia is detectable and RT-PCR sensitivity is highest. After day 6, detection of specific immunoglobulin M or documented seroconversion becomes more informative for diagnostic confirmation.
For symptomatic pregnant women, the review recommends a multiplex panel that detects Oropouche virus, dengue, Zika, chikungunya, and Mayaro viruses because of the substantial clinical overlap among these arboviruses. Preferred samples include maternal blood during the acute phase and, when neurologic symptoms are present, cerebrospinal fluid.
Oropouche infection typically begins suddenly with high fever (38-40 °C), intense headache, diffuse myalgias, and prominent gastrointestinal symptoms — nausea, vomiting, and diarrhea are more frequent than with Zika or chikungunya. A distinguishing feature is a biphasic illness pattern: after an initial improvement, symptoms recur after 7-14 days, a phenomenon less common in other arboviruses. A maculopapular rash, common in Zika, is uncommon in Oropouche.
Fetal Monitoring Protocol
For pregnant women with confirmed or suspected infection, the review recommends immediate referral to high-risk prenatal care and close ultrasound surveillance. Evaluation should occur every 4 weeks, with detailed neurosonography and special attention to ventriculomegaly, intracranial calcifications, and posterior fossa malformations. Early detection of structural changes can precede overt microcephaly, reinforcing the need for serial surveillance throughout pregnancy.
Monitoring should also include assessment of fetal growth and fundal height. If intrauterine growth restriction is suspected, umbilical artery Doppler velocimetry is indicated, with additional ductus venosus assessment when necessary. Fetal magnetic resonance imaging may be considered when ultrasound detects central nervous system anomalies, to refine diagnosis and aid prognostic counseling.
Follow-up frequency: Ultrasound every 4 weeks
Primary focus: Detailed neurosonography to detect:
• Ventriculomegaly
• Intracranial calcifications
• Posterior fossa malformations
• Agenesis/dysgenesis of the corpus callosum
Additional evaluations:
• Fetal growth and fundal height
• Umbilical artery Doppler (if fetal growth restriction is suspected)
• Ductus venosus Doppler (when indicated)
• Fetal MRI (if abnormalities are detected on ultrasound)
Not recommended: diagnostic amniocentesis (restricted to research protocols)
Perinatal Management and Neonatal Evaluation
The route of delivery should follow conventional obstetric guidelines. A C-section is not recommended solely because of Oropouche infection. When prenatal anomalies are detected, delivery planning should involve a neonatologist and neurodevelopmental specialists.
At birth, collection of maternal and neonatal blood, placental tissue, and umbilical-cord samples is recommended even for asymptomatic pregnant women who reside in endemic areas, for epidemiologic surveillance and research purposes. In cases of stillbirth or spontaneous abortion, investigation should include histopathologic and molecular analysis of fetal tissues and placenta,with broad testing for STORCH pathogens — syphilis, toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus — plus Zika and other arboviruses.
Complete neonatal evaluation should include a detailed neurologic and musculoskeletal exam, with attention to signs of arthrogryposis. If microcephaly or neurologic signs are present, cranial ultrasound should be performed. A full ophthalmologic exam and newborn hearing screening are mandatory because of the potential for sensory impairment. When neurologic signs or confirmed malformations exist, lumbar puncture with cerebrospinal fluid analysis may be considered.
Neonates with confirmed congenital infection require long-term, multidisciplinary follow-up because neurologic and developmental sequelae can appear later. Breastfeeding is not contraindicated in these cases.
Mandatory Reporting
Oropouche fever is a reportable disease in Brazil. All suspected or confirmed cases in pregnant women must be reported through Brazil’s e-SUS Sinan system using 10th revision of the International Classification of Diseases (ICD-10) code A93.0. Reporting is also required for fetuses or newborns with central nervous system malformations of unknown etiology when there is suspected maternal exposure in areas with documented viral circulation.
Treatment and Clinical Management
There is no specific antiviral treatment. Clinical management is supportive and includes rest, hydration, and acetaminophen for symptom control. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, are contraindicated because of the bleeding risk if dengue co-infection is present — a crucial precaution given the co-circulation of arboviruses in the region.
Hospitalization is recommended for patients with hemorrhagic, neurologic, or systemic complications, or for those with comorbidities such as diabetes, hypertension, or immunosuppression.
Prevention and Vector Control
In the absence of a licensed vaccine, prevention is based on vector control and individual protection. Oropouche virus is transmitted mainly by the sandfly (Culicoides paraensis) — a crepuscular insect particularly abundant in rural and peri-urban areas with accumulated organic matter. Culex mosquitoes may act as secondary vectors.
Recommendations include wearing long sleeves, long pants, socks, and closed shoes, especially during peak vector activity (dawn and dusk). Installing screens with mesh smaller than 1.5 mm on windows and doors can reduce indoor vector entry. Insecticide-treated bed nets are recommended in high-transmission areas. Use of registered repellents is advised, although data on their specific efficacy against Culicoides are limited — the recommendation is also justified by the co-circulation of other arboviruses transmitted by Aedes mosquitoes.
Pregnant women in agricultural areas should avoid gardening, clearing crops or exposure to sites with decaying plant material during peak vector activity. Cleaning peridomestic areas and removing fallen leaves, rotting fruit and other organic matter — particularly around banana, cocoa and coffee crops — reduces breeding sites for the sandfly.
Although sexual transmission has not been confirmed, viral RNA has been detected in the semen of infected patients. As a precaution, use of condoms or abstinence is recommended for at least 6 weeks after symptom resolution. Blood donors should defer donation for at least 4 weeks after full recovery. Pregnant women are advised to reconsider nonessential travel to areas with active Oropouche transmission.
Implications for Clinical Practice
Incorporating Oropouche into diagnostic algorithms for febrile illness in pregnancy is necessary and urgent in regions where the virus is endemic. Mandatory reporting must be strictly followed to build a robust evidence base on the infection’s natural history during pregnancy.
Serial ultrasound surveillance focused on the central nervous system enables early detection of structural abnormalities and guides family counseling. Involvement of a multidisciplinary team — obstetricians, neonatologists, neurologists, ophthalmologists, and rehabilitation professionals — is essential for appropriate case management and long-term follow-up of children exposed to the pathogen.
Special attention should be given to vulnerable populations — incarcerated women, those experiencing homelessness, migrants, refugees, and members of Indigenous or quilombola communities (quilombola communities are Afro-Brazilian settlements descended from escaped enslaved people and often have limited access to health services) — ensuring equitable access to high-risk prenatal care, diagnostic testing, transportation and follow-up. Clear communication with pregnant women about risks, preventive measures, and the importance of early diagnosis is the responsibility of all prenatal care providers in at-risk areas.
According to the Ministry of Health’s epidemiologic dashboard, Brazil recorded 11,988 confirmed cases of Oropouche in 2025, with five confirmed deaths and two under investigation. However, cases were concentrated in the first half of the year, with a marked decline in recent epidemiologic weeks.
Key Points for Practice:
• Include Oropouche in the differential diagnosis of febrile illness during pregnancy in endemic areas
• RT-PCR between 2 and 7 days after symptom onset (critical diagnostic window)
• Ultrasound every 4 weeks with focused neurosonography
• Amniocentesis not standard (restricted to research)
• NSAIDs contraindicated (risk for undiagnosed dengue co-infection)
• Collect samples at birth even from asymptomatic patients in endemic areas
• Mandatory reporting required (ICD-10 A93.0)
• Ensure access to care for vulnerable populations
Roseane Santos is a Brazilian journalist with 35 years’ experience who has worked for major national outlets like Universo Online (UOL), the daily newspaper Folha de S.Paulo, and Portal Terra, and contributes to scientific publications from Albert Einstein Israelite Hospital and the Brazil’s National Cancer Institute.
This story was translated from Medscape’s Portuguese edition.
