Development of Secondary #Microcephaly After #Delivery: Possible Consequence of #Mother- #Baby #Transmission of #Zika Virus in #Breast #Milk (Am J Case Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Am J Case Rep. 2019 May 21;20:723-725. doi: 10.12659/AJCR.915726.

Development of Secondary Microcephaly After Delivery: Possible Consequence of Mother-Baby Transmission of Zika Virus in Breast Milk.

Siqueira Mello A1, Pascalicchio Bertozzi APA2, Rodrigues MMD2, Gazeta RE2, Moron AF3, Soriano-Arandes A4, Sarmento SGP3, Vedovello D1, Silva ACB1, Grillo Fajardo TC1, Witkin SS5, Passos SD2,1.

Author information: 1 Laboratory of Pediatric Infectology, Department of Pediatrics, Jundiaí School of Medicine, São Paulo, SP, Brazil. 2 Department of Pediatrics, Jundiaí School of Medicine, São Paulo, SP, Brazil. 3 Department of Obstetrics, Federal University of São Paulo (UNIFESP) – Paulista School of Medicine and Paulista Center for Fetal Medicine, São Paulo, SP, Brazil. 4 Paediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Barcelona, Spain. 5 Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York City, NY, USA.




The Zika virus is an arbovirus that has as main source of transmission the bite of infected insects of the genus Aedes and has been associated with cases of congenital malformation and microcephaly in neonates. However, other sources of transmission have been identified since the emergence of this virus in the world population, such as vertical transmission by semen and possibly other body fluids such as vaginal secretion and breast milk.


An infant, born to a mother whose previous delivery was a baby with severe microcephaly, was normal and was negative for Zika virus at birth but developed secondary microcephaly 1 month later, that persisted. The baby was exclusively breast-fed and Zika virus was present in the mother’s milk.


We report the detection of Zika virus exclusively in the breast milk of a woman after her second delivery of an infant, who later developed microcephaly. This case is consistent with possible vertical transmission.

PMID: 31110169 DOI: 10.12659/AJCR.915726

Keywords: Zika Virus; Pregnancy; Microcephaly.



The #challenge of the #laboratory #diagnosis in a confirmed #congenital #Zika virus #syndrome in #utero: A case report (Medicine (Baltimore), abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Medicine (Baltimore). 2019 May;98(20):e15532. doi: 10.1097/MD.0000000000015532.

The challenge of the laboratory diagnosis in a confirmed congenital Zika virus syndrome in utero: A case report.

Sulleiro E1,2, Frick MA1,2, Rodó C1,2, Espasa M1, Thorne C2,3, Espiau M1,2, Martín-Nalda A1,2, Suy A1,2, Giaquinto C2,4, Melendo S1, Rando A1, Alarcón A2,5, Martinón-Torres F2,6, Pumarola T1, Soler-Palacín P1, Soriano-Arandes A1,2.

Author information: 1 Hospital Universitari Vall d’Hebron, Barcelona, Spain. 2 ZIKAction Consortium, European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No 734857. 3 University College London, London, United Kingdom. 4 University of Padova, PENTA Foundation, Padova, Italy. 5 Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain. 6 Hospital Clínico Universitario, Santiago de Compostela, Spain.




Zika virus (ZIKV) has caused one of the most challenging global infectious epidemics in recent years because of its causal association with severe microcephaly and other congenital malformations. The diagnosis of viral infections usually relies on the detection of virus proteins or genetic material in clinical samples as well as on the infected host immune responses. Serial serologic testing is required for the diagnosis of congenital infection when diagnostic molecular biology is not possible.


A 2-year-old girl, born to a mother with confirmed ZIKV infection during pregnancy, with a confirmed ZIKV infection in utero, showed at birth a severe microcephaly and clinical characteristics of fetal brain disruption sequence compatible with a congenital ZIKV syndrome (CZS).


ZIKV-RNA and ZIKV-IgM serological response performed at birth and during the follow-up time tested always negative. Serial serologic ZIKV-IgG tests were performed to assess the laboratory ZIKV diagnosis, ZIKV-IgG seroreversion was observed at 21 months of age. ZIKV diagnosis of this baby had to be relied on her clinical and radiological characteristics that were compatible with a CZS.


The patient was followed-up as per protocol at approximately 1, 4, 9, 12, 18-21, and 24 months of age. Neurological, radiological, audiological, and ophthalmological assessment were performed during this period of time. Prompt rehabilitation was initiated to prevent potential adverse long-term neurological outcomes.


The growth of this girl showed a great restriction at 24 months of age with a weight of 8.5 kg (-2.5 z-score) and a head circumference of 40.5 cm (-4.8 z-score). She also had a great neurodevelopmental delay at the time of this report.


We presume that as a consequence of prenatal ZIKV infection, the fetal brain and other organs are damaged before birth through direct injury. Following this, active infection ends during intrauterine life, and as a consequence the immune system of the infant is unable to build up a consistent immune response thereafter. Further understanding of the mechanisms taking part in the pathogenesis of ZIKV congenital infection is needed. This finding might change our paradigm regarding serological response in the ZIKV congenital infection.

PMID: 31096455 DOI: 10.1097/MD.0000000000015532

Keywords: Zika Virus; Zika Congenital Syndrome; Microcephaly; Serology.


Reporting of #birth #defects from the #Zika #outbreak in #Colombia, 2015-2017 (Rev Panam Salud Publica, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Rev Panam Salud Publica. 2019 May 3;43:e38. doi: 10.26633/RPSP.2019.38. eCollection 2019.

[Reporting of birth defects from the Zika outbreak in Colombia, 2015-2017]

Notificação de defeitos congênitos associados ao surto de vírus zika na Colômbia, 2015-2017].

[Article in Spanish]

Mendivelso Duarte FO1, Robayo García A2, Rodríguez Bedoya M3, Suárez Rángel G2.

Author information: 1 Centro de Medicina Basada en la Evidencia Keralty Centro de Medicina Basada en la Evidencia Keralty Bogotá Colombia Centro de Medicina Basada en la Evidencia Keralty, Bogotá, Colombia. 2 Programa de Entrenamiento en Epidemiología de Campo (FETP) del Instituto Nacional de Salud de Colombia Programa de Entrenamiento en Epidemiología de Campo (FETP) del Instituto Nacional de Salud de Colombia Colombia Colombia Programa de Entrenamiento en Epidemiología de Campo (FETP) del Instituto Nacional de Salud de Colombia, Colombia. 3 Fundación Universitaria Sanitas Fundación Universitaria Sanitas Bogotá Colombia Fundación Universitaria Sanitas, Bogotá, Colombia.


Abstract in English, Portuguese


The Zika outbreak affected several tropical countries in 2015 and 2016, requiring the creation of intensified surveillance strategies for microcephaly and other neurological syndromes. The effect of the Zika outbreak on the reporting of birth defects in Colombia was evaluated from the perspective of the national surveillance system.


National reporting of newborns with different birth defects was analyzed; variations in reporting attributed to the epidemic were determined through difference in differences (DID), a semiparametric model.


During the period of study, 18,234 cases of birth defects were reported in Colombia. The majority were congenital malformations (91.9%), and 82.3% was confirmed by clinical diagnosis or epidemiological link. In the case of microcephaly, eight new cases per epidemiological week were reported (coefficient of case reporting [D] = 8.8; P = 0.000) and 32 cases from other congenital anatomical malformations (D = 32.0; P = 0.000). The absolute value of the difference in differences estimator attributed to the Zika outbreak increased weekly case reporting of microcephaly (DID = |-5.0|; P = 0.008) and congenital malformations (DID = |-12.0|; P = 0.111).


The Zika outbreak increased reporting of newborns with microcephaly, but caused no significant variation in reporting of other malformations and functional birth defects of sensory or metabolic origin in the surveillance system.

KEYWORDS: Colombia; Zika virus; congenital abnormalities; health surveillance; public health

PMID: 31093262 PMCID: PMC6499088 DOI: 10.26633/RPSP.2019.38

Keywords: Zika Virus; Zika Congenital Syndrome; Microcephaly; Colombia.


#Congenital #Zika Syndrome: The Main Cause of #Death and Correspondence Between #Brain #CT and Postmortem #Histological Section Findings From the Same Individuals (Top Magn Reson Imaging, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Top Magn Reson Imaging. 2019 Feb;28(1):29-33. doi: 10.1097/RMR.0000000000000194.

Congenital Zika Syndrome: The Main Cause of Death and Correspondence Between Brain CT and Postmortem Histological Section Findings From the Same Individuals.

de Fatima Viana Vasco Aragão M1,2, van der Linden V3, Petribu NC3, Valenca MM4, Parizel PM5,6, de Mello RJV4.

Author information: 1 Multimagem, Recife, Brazil. 2 Catholic University of Pernambuco, Recife, Brazil. 3 Barão de Lucena Hospital, Recife, Brazil. 4 Federal University of Pernambuco, Recife, Brazil. 5 Royal Perth Hospital (RPH), Perth, WA, Australia. 6 University of Western Australia (UWA) Medical School, Perth, WA, Australia.



In the present case series, the cause of death of infants diagnosed with congenital Zika syndrome (CZS) was lung disease (pneumonia and sepsis with massive pulmonary aspiration), probably secondary to dysphagia and reflux. The main findings in infants with a confirmed diagnosis of CZS who died were as follows: (1) calcification and hypoplasia of the lentiform nuclei, hypoplasia of the caudate nuclei, and calcification at the cortical-subcortical junction was noted in all cases (100%) and calcification of the caudate nuclei was noted in 66.7% of cases; (2) calcification in the brainstem and along the lateral wall of the lateral ventricles was noted in only the case with arthrogryposis (33.3%); and (3) lesions in the posterior fossa (hypoplasia of the brainstem and cerebellum) were noted in two cases (66.7%), including the case with arthrogryposis. The findings concerning calcifications and brain malformations obtained from non-contrast computed tomography (CT) demonstrated good agreement with findings obtained from the postmortem pathological analysis; however, CT failed to detect discontinuity of the pia mater with heterotopia, invasion of the cerebral tissue into the subarachnoid space, and discontinuity of the ependyma in the lateral ventricles with gliosis; this last feature was only imaged in the most severe case of extreme microcephaly with a simplified gyral pattern. Only histopathology showed grouped calcifications associated with scattered calcifications suggestive of the neuron morphology.

PMID: 30817678 DOI: 10.1097/RMR.0000000000000194 [Indexed for MEDLINE]

Keywords: Congenital Zika Syndrome; Zika Virus; Microcephaly; Histopathology; Neurology; Neuroimaging.


#Children Born to #Mothers with #Rash During #Zika Virus #Epidemic in #Brazil: First 18 Months of Life (J Trop Pediatr., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Trop Pediatr. 2019 Apr 21. pii: fmz019. doi: 10.1093/tropej/fmz019. [Epub ahead of print]

Children Born to Mothers with Rash During Zika Virus Epidemic in Brazil: First 18 Months of Life.

Vianna RAO1, Lovero KL2, Oliveira SA1, Fernandes AR1, Santos TCSD1, Lima LCSS1, Carvalho FR1, Quintans MDS1, Bueno AC1, Torbey AFM1, Souza ALAAG1, Farias AOP1, Camacho LAB3, Riley LW4, Cardoso CAA1.

Author information: 1 Faculdade de Medicina, Universidade Federal Fluminense, RJ 24.033-900, Brazil. 2 Department of Psychiatry, University of Columbia, New York 10032, USA. 3 Departamento de Epidemiologia e Métodos Quantitativos em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, RJ 21.041-210, Brazil. 4 Division of Infectious Diseases and Vaccinology, University of California, Berkeley 94720, USA.




To better understand the clinical spectrum and course of congenital Zika syndrome (CZS) during the first 18 months of life of children whose mothers had rash during pregnancy.


This longitudinal observational study evaluated the clinical progress from birth until 18 months of life of children of mothers who developed rash during or up to 3 months before gestation. Maternal rash occurred from November 2015 to May 2017. The study subjects were divided into three groups: children whose mothers tested positive by RT-qPCR for Zika virus (ZIKV) (Group 1), children whose mothers tested negative by RT-qPCR for ZIKV (Group 2), and children whose mothers did not undergo any testing for ZIKV (Group 3) but tested negative for other congenital infections.


Between April 2016 and July 2018, we studied 108 children: 43 in Group 1, 26 in Group 2 and 39 in Group 3. The majority of children were admitted into the study within 6 months of life. CZS was diagnosed in 26 children, equally distributed in Groups 1 and 3. Of 18 children with microcephaly, 6 were in Group 1 (1 postnatal) and 12 were in Group 3 (5 postnatal). Maternal rash frequency was 10 times higher during the first trimester than in the other trimesters (OR: 10.35; CI 95%: 3.52-30.41). CZS was diagnosed during the follow-up period in 14 (54%) cases. Developmental delays and motor abnormalities occurred in all children and persisted up to 18 months. Epilepsy occurred in 18 (69%) of the cases.


Infants born of mothers exposed to ZIKV during pregnancy showed progression of developmental, motor and neurologic abnormalities even if they were born asymptomatic. Continued postnatal monitoring of such newborns is necessary to preclude disability-associated complications.

© The Author(s) [2019]. Published by Oxford University Press. All rights reserved. For permissions, please email:

KEYWORDS: Congenital Zika syndrome; RT-PCR; Zika virus; microcephaly

PMID: 31006031 DOI: 10.1093/tropej/fmz019

Keywords: Zika Virus; Zika Congenital Infection; Zika Congenital Syndrome; Microcephaly; Pregnancy; Brazil.


#Outcomes of #Congenital #Zika Virus Infection During an #Outbreak in Valle del Cauca, #Colombia (Pediatr Infect Dis J., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Pediatr Infect Dis J. 2019 Apr 10. doi: 10.1097/INF.0000000000002307. [Epub ahead of print]

Outcomes of Congenital Zika Virus Infection During an Outbreak in Valle del Cauca, Colombia.

Calle-Giraldo JP1, Rojas CA2, Hurtado IC2,3,4, Barco C2, Libreros D5,6, Sánchez PJ7, López P2,8, Arias A6, Dávalos DM9, Lesmes MC4, Pinzón E4, Ortiz VA4, López-Medina E2,6,8.

Author information: 1 From the Department of Pediatrics, Universidad del Quindío, Armenia, Colombia. 2 Department of Pediatrics, Universidad del Valle, Cali, Colombia. 3 Hospital Universitario del Valle, Cali, Colombia. 4 Department of Health, Valle del Cauca. Cali, Colombia. 5 Department of Ophthalmology, Universidad del Valle, Cali, Colombia. 6 Centro Médico Imbanaco. Cali, Colombia. 7 Department of Pediatrics, Nationwide Children´s Hospital, The Ohio State University College of Medicine, Columbus, Ohio. 8 Centro de Estudios en Infectología Pediátrica. Cali, Colombia. 9 Department of Public Health, Universidad Icesi, Cali, Colombia.




Despite increasing information in the literature regarding congenital Zika infection, gaps remain in our knowledge of its clinical manifestations.


We did a prospective observational study of exposed fetuses and infants whose mothers developed symptomatic and confirmed Zika infection during pregnancy in Valle del Cauca, Colombia. We performed neurological, ophthalmological and audiological evaluations, and classified outcomes as possibly or uncertainly related to Zika. Frequencies of outcomes were compared according to the trimester of pregnancy when infection occurred.


We evaluated 171 products of gestation including 17 pregnancy losses and 154 patients evaluated postnatally. Ninety (52.6%) pregnancies presented an adverse outcome, 36% possibly related with Zika and the remaining 64% of uncertain relation. Infection in the first trimester had the highest frequencies of adverse outcomes possibly related with Zika compared with the second and third trimesters (39% vs. 12.5% vs. 12%) with risk ratios of adverse outcomes possibly related to Zika in pregnancies infected in the first versus second or third trimester of 3.1 (95% CI: 2.4-4.1) and 3.3 (95% CI: 2.5-4.2), respectively. The frequencies of pregnancy loss and microcephaly were 9.4% and 4.5%, respectively. Auditory and ophthalmic abnormalities possibly related with Zika were present in 3% and 6% of the patients evaluated, respectively.


We observed a high frequency of gestational and neonatal complications in pregnant women who acquired Zika infection, especially in early pregnancy, resulting in a broad spectrum of clinical manifestations. Preventive measures are urgently needed to reduce the clinical burden during future Zika outbreaks.

PMID: 30985517 DOI: 10.1097/INF.0000000000002307

Keywords: Zika Virus; Pregancy; Zika Congenital Infection; Zika Congenital Syndrome; Microcephaly; Colombia.


The #Unfolded #Protein Response: A Key #Player in #Zika Virus-Associated Congenital #Microcephaly (Front Cell Neurosci., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Front Cell Neurosci. 2019 Mar 26;13:94. doi: 10.3389/fncel.2019.00094. eCollection 2019.

The Unfolded Protein Response: A Key Player in Zika Virus-Associated Congenital Microcephaly.

Alfano C1, Gladwyn-Ng I1, Couderc T2,3, Lecuit M2,3,4, Nguyen L1.

Author information: 1 GIGA-Stem Cells, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, Liège, Belgium. 2 Institut Pasteur, Biology of Infection Unit, Paris, France. 3 INSERM U1117, Biologie des Infections, Paris, France. 4 Paris Descartes University, Division of Infectious Diseases and Tropical Medicine, Necker-Enfants Malades Hospital, Institut Imagine, Sorbonne Paris Cité, Paris, France.



Zika virus (ZIKV) is a mosquito-borne virus that belongs to the Flaviviridae family, together with dengue, yellow fever, and West Nile viruses. In the wake of its emergence in the French Polynesia and in the Americas, ZIKV has been shown to cause congenital microcephaly. It is the first arbovirus which has been proven to be teratogenic and sexually transmissible. Confronted with this major public health challenge, the scientific and medical communities teamed up to precisely characterize the clinical features of congenital ZIKV syndrome and its underlying pathophysiological mechanisms. This review focuses on the critical impact of the unfolded protein response (UPR) on ZIKV-associated congenital microcephaly. ZIKV infection of cortical neuron progenitors leads to high endoplasmic reticulum (ER) stress. This results in both the stalling of indirect neurogenesis, and UPR-dependent neuronal apoptotic death, and leads to cortical microcephaly. In line with these results, the administration of molecules inhibiting UPR prevents ZIKV-induced cortical microcephaly. The discovery of the link between ZIKV infection and UPR activation has a broader relevance, since this pathway plays a crucial role in many distinct cellular processes and its induction by ZIKV may account for several reported ZIKV-associated defects.

KEYWORDS: ER stress; Zika virus; cerebral cortex; cortical progenitors; microcephaly; unfolded protein response

PMID: 30971894 PMCID: PMC6445045 DOI: 10.3389/fncel.2019.00094

Keywords: Zika Virus; Microcephaly; Viral pathogenesis.