Pathology of congenital Zika syndrome in Brazil: a case series

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Pathology of congenital Zika syndrome in Brazil: a case series Roosecelis Brasil Martines, MD, Julu Bhatnagar, PhD, Prof Ana Maria de Oliveira Ramos, MD, Helaine Pompeia Freire Davi, MD, Silvia D'Andretta Iglezias, MD, Cristina Takami Kanamura, MSc, M Kelly Keating, DVM, Gillian Hale, MD, Luciana Silva-Flannery, PhD, Atis Muehlenbachs, MD, Jana Ritter, DVM, Joy Gary, DVM, Dominique Rollin, MD, Cynthia S Goldsmith, MGS, Sarah Reagan-Steiner, MD, Yokabed Ermias, MPH, Tadaki Suzuki, MD, Prof Kleber G Luz, MD, Wanderson Kleber de Oliveira, MSc, Robert Lanciotti, PhD, Amy Lambert, PhD, Wun-Ju Shieh, MD, Dr Sherif R Zaki, MD The Lancet Volume 388, Issue 10047, Pages 898-904 (August 2016) DOI: 10.1016/S0140-6736(16)30883-2 Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 1 Congenital Zika syndrome (A, B) Case 1 showing craniofacial malformations, including microcephaly, flat nasal bridge, anteverted nares, and features of fetal akinesia deformation sequence with upper and lower limb contractures and valgus deformities. (C) Case 2 at autopsy showing levoscoliosis and gross examination of the brain (D) displaying two underdeveloped hemispheres with lissencephaly (short arrow) and ventriculomegaly (arrowheads) of the lateral ventricle. Cerebellar hypoplasia is also evident in the exposed left cerebellar hemisphere (long arrow). The Lancet 2016 388, 898-904DOI: (10.1016/S0140-6736(16)30883-2) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 2 Case 3—histopathological and immunohistochemical findings in the brain (A) Microscopic examination of the brain tissue shows a subcortical band-like pattern of degenerating cells associated with calcifications; haematoxylin-eosin stain. (B) Calcifications distributed throughout the cortex; haematoxylin-eosin stain. (C) Degenerating neural cells within the cortex (arrowheads); haematoxylin-eosin stain. (D) Zika viral antigens detected by immunohistochemistry in areas of calcifications; inset; high magnification of calcifications. (E) High magnification of degenerating neural cell highlighted by Zika virus immunohistochemical assay. (F) Perinuclear staining of glial cells by Zika virus immunohistochemistry. The Lancet 2016 388, 898-904DOI: (10.1016/S0140-6736(16)30883-2) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 3 Case 4—histopathological and immunohistochemical findings of the placenta (A) Low magnification of an 11-week placenta with massive chronic intervillositis and fibrin deposition; haematoxylin-eosin stain. (B) Zika virus immunolocalised in Hofbauer cells (arrowheads) and in association with karyorrhectic debris of the chorionic villi. The Lancet 2016 388, 898-904DOI: (10.1016/S0140-6736(16)30883-2) Copyright © 2016 Elsevier Ltd Terms and Conditions