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Newborns with microcephaly in Brazil and potential vertical transmission of Oropouche virus: a case series - 16/10/24

Doi : 10.1016/S1473-3099(24)00617-0 
Fernanda Eduarda das Neves Martins, MSc a, Jannifer Oliveira Chiang, PhD a, Bruno Tardelli Diniz Nunes, PhD a, Bethania de Freitas Rodrigues Ribeiro, MD MSc b, Lívia Carício Martins, PhD a, Lívia Medeiros Neves Casseb, PhD a, Daniele Freitas Henriques, PhD a, Consuelo Silva de Oliveira, ProfMSc a, Ethel Leonor Noia Maciel, PhD c, Rafael da Silva Azevedo, MD a, Layna de Cássia Campos Cravo, MSc a, André Rodrigues Façanha Barreto, ProfMD d, André Luiz Santos Pessoa, ProfMD PhD e, f, Arnaldo Jorge Martins Filho, PhD g, Jorge Rodrigues de Sousa, ProfPhD h, Lavinia Schuler-Faccini, ProfMD PhD i, j, Juarez Antônio Simões Quaresma, ProfMD PhD g, h, k, Pedro Fernando da Costa Vasconcelos, ProfMD PhD a, h, , Raimunda do Socorro da Silva Azevedo, MD PhD a,
a Department of Arbovirology and Hemorrhagic Fever, Evandro Chagas Institute, Ananindeua, Pará, Brazil 
b Maternidade e Clínica de Mulheres Bárbara Heliodora, Secretaria de Estado de Saúde do Acre, Rio Branco, Acre, Brazil 
c Secretary of Health Surveillance of the Brazilian Ministry of Health, Brasília, DF, Brazil 
d Radiology Department, Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil 
e Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil 
f Hospital Infantil Albert Sabin, Secretaria de Saúde do Estado do Ceará, Fortaleza, Ceará, Brazil 
g Department of Pathology, Evandro Chagas Institute, Ananindeua, Pará, Brazil 
h Department of Pathology, Pará State University, Belém, Pará, Brazil 
i Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil 
j Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil 
k Núcleo de Medicina Tropical, Universidade Federal do Pará, Pará, Brazil 

* Correspondence to: Prof Pedro Fernando da Costa Vasconcelos, Department of Pathology, Pará State University, Belém, Pará CEP 66087-662, Brazil Department of Pathology Pará State University Belém Pará CEP 66087-662 Brazil ** Dr Raimunda do Socorro da Silva Azevedo, Department of Arbovirology and Hemorrhagic Fever, Evandro Chagas Institute, Ananindeua, Pará CEP 67030-000, Brazil Department of Arbovirology and Hemorrhagic Fever Evandro Chagas Institute Ananindeua Pará CEP 67030-000 Brazil
Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 16 October 2024

Summary

Background

Oropouche fever, an orthobunyavirus disease endemic in Brazilian Amazon, has caused many febrile epidemics. In 2024, an epidemic of Oropouche fever spread in Brazil, with more than 7930 cases reported between Jan 1 and Aug 31. Infections in pregnant people have suggested the possibility of negative fetal consequences, therefore we tested newborns with microcephaly for known congenital pathogens and Oropouche virus (OROV).

Methods

In this case series, we assessed historical cases of infants born with microcephaly, arthrogryposis, and other congenital malformations without a confirmed cause and their mothers for potential OROV congenital infections. The study population consisted of infants born in Brazil with samples from 2015–21 and 2024. Serum and cerebrospinal fluid (CSF) from this case series were analysed for: syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes simplex, HIV, Zika, dengue, and chikungunya. Individuals that were negative for these pathogens were then tested for OROV. Pathogen testing included ELISA and haemagglutination inhibition testing for antibodies and RT-PCR for virus RNA.

Findings

We tested 68 samples from 65 historical cases of congential malformations and three cases from 2024. All cases were from ten states in Brazil. Three historical cases tested positive for OROV and 62 historical cases tested negative. The three cases from 2024 all tested positive for OROV. Of the positive cases, five were female and one was male. Not all pathogens were tested for each case, and some did not have maternal samples available. One of the newborns (case 6) died aged 47 days and tissue samples were tested by real-time RT-PCR, histopathology, and immunohistochemistry assays. One other newborn died in 2016 but no post-mortem samples were available. OROV IgM was detected in five of five newborn CSF samples, and five of five newborn serum samples. Four of five maternal serum samples were positive for OROV IgM. One of four newborn CSF samples (case 6 at age 44 days) was OROV positive by real-time RT-quantitative PCR and 0 of four newborn serum samples were positive, as were 0 of three maternal serum samples. Case 6 had major tissue changes of the brain macroscopically and microscopically, including necrotic and apoptotic changes of neurons, microglia and astrocytes, vacuolisation, and tissue atrophy. OROV RNA was detected in brain, lungs, kidney, CSF, and pleural fluid; OROV antigens were found in CNS, liver, kidney, heart, and lung, mainly in neurons and microglia and also in endothelial cells, suggesting vasculitis.

Interpretation

We detected OROV IgM in six of 68 newborns with microcephaly of unknown cause. One infant who died had OROV RNA and antigen in several tissues, including the brain. The possibility of OROV vertical transmission and potential fetal harm must be investigated with urgency. The evidence presented here does not completely confirm vertical transmission or congenital malformations due to OROV, but thorough case finding and detailed investigation of maternal or fetal OROV infection is a priority.

Funding

Evandro Chagas Institute, Secretaria de Vigilância em Saúde e Ambiente, and Ministry of Health and National Institute of Science and Technology for Emerging and Reemerging Viruses.

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