Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Nov 28;7(12):496.
doi: 10.3390/jcm7120496.

Zika Virus Epidemic in Brazil. II. Post-Mortem Analyses of Neonates with Microcephaly, Stillbirths, and Miscarriage

Raimunda S S Azevedo  1 , Marialva T Araujo  2 , Consuelo S Oliveira  3   4 , Arnaldo Jorge Martins Filho  5 , Bruno T D Nunes  6 , Daniele F Henriques  7 , Eliana V P Silva  8 , Valéria L Carvalho  9 , Jannifer O Chiang  10 , Lívia C Martins  11 , Barbara C B Vasconcelos  12 , Jorge R Sousa  13   14 , Fernanda Montenegro C Araujo  15 , Erlane M Ribeiro  16 , Andrezza R P Castro  17 , Maria G L de Queiroz  18 , Mariana P Verotti  19 , Márcio R T Nunes  20 , Ana C R Cruz  21 , Sueli G Rodrigues  22 , Pei-Yong Shi  23 , Juarez A S Quaresma  24   25 , Robert B Tesh  26 , Pedro F C Vasconcelos  27   28
Affiliations

Zika Virus Epidemic in Brazil. II. Post-Mortem Analyses of Neonates with Microcephaly, Stillbirths, and Miscarriage

Raimunda S S Azevedo et al. J Clin Med. .

Abstract

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.

Keywords: ZIKV RNA; Zika virus; and ZIKV antigen; congenital syndrome; microcephaly.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Histopathological aspects and positive immunostaining of the ZIKV-infectedmiscarriage (Case 1). (A) Embryonic tissue (black arrow) within the yolk sac (blue arrow) and placenta (red arrow) (HE, 100×). (B) Positive immunostaining for ZIKV antigens in embryonic tissue (IHC, SAAP, 400×). (C,D) Positive immunostaining for ZIKV in placental chorionic villi (IHC, SAAP, 400×). (E) Positive immunostaining to ZIKV observed in the liver in hepatocytes (circle) (Case 3) (IHC, SAAP, 400×). (F) Positive immunostaining to ZIKV observed in the kidney in renal tubule (black arrows) (Case 3) (IHC, SAAP, 400×).
Figure 2
Figure 2
Representative histopathological changes and positive immunostaining in central nervous tissue of ZIKV-positive microcephaly cases by ZIKV. (A,B) Cellular disorganization in the cortical layer and positive immunostaining (arrow) for ZIKV antigen in neurons (Case 4) (IHC, SAAP, 400×). (C) Foci of dystrophic calcification in parenchyma with degenerative necrotic lesion (Case 6) (HE, 400×). (D) Gliosis in parenchyma with degenerative necrotic lesion (Case 6) (HE, 400×). (E,F) Positive immunostaining for ZIKV in neurons and astrocytes with perivascular inflammatory infiltrate (Case 6) (IHC, SAAP, 400×). (G) Significant vascular proliferation, edema and vessel congestion (arrows) (Case 11) (HE, 100×). (H) Pyramidal neurons of the cerebral cortex with neuronophagy, satelitosis, and gliosis (circles) (Case 11) (HE, 400×).
Figure 3
Figure 3
Newborn with 29 weeks gestational age showing microcephaly and arthrogryposis. The infantdied 5 min after birth (Case 10).
See this image and copyright information in PMC

References

    1. Dick G.W., Kitchen S., Haddow A. Zika Virus (I). Isolations and serological specificity. Trans. R. Soc. Trop. Med. Hyg. 1952;46:509–520. doi: 10.1016/0035-9203(52)90042-4. - DOI - PubMed
    1. Hayes E.B. Zika Virus Outside Africa. Emerg. Infect. Dis. 2009;15:1347–1350. doi: 10.3201/eid1509.090442. - DOI - PMC - PubMed
    1. Oehler E., Watrin L., Larre P., Leparc-Goffart I., Lastere S., Valour F., Baudouin L., Mallet H., Musso D., Ghawche F. Zika virus infection complicated by Guillain-Barre syndrome—Case report, French Polynesia, December 2013. Euro Surveill. 2014;19:7–9. doi: 10.2807/1560-7917.ES2014.19.9.20720. - DOI - PubMed
    1. Pan American Health Organization (PAHO)/World Health Organization (WHO) Zika—Epidemiological Update, 25 August 2017. PAHO/WHO; Washington, DC, USA: 2017.
    1. Campos G.S., Bandeira A.C., Sardi S.I. Zika Virus Outbreak, Bahia, Brazil. Emerg. Infect. Dis. 2015;21:1885–1886. doi: 10.3201/eid2110.150847. - DOI - PMC - PubMed

LinkOut - more resources