#Seroprevalence of #Zika virus among asymptomatic #pregnant mothers and their #newborns in the #Najran region of southwest #Saudi Arabia (Ann Saudi Med., abstract)

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

Ann Saudi Med. 2018 Nov-Dec;38(6):408-412. doi: 10.5144/0256-4947.2018.408.

Seroprevalence of Zika virus among asymptomatic pregnant mothers and their newborns in the Najran region of southwest Saudi Arabia.

Alayed MS, Qureshi MA, Ahmed S, Alqahtani AS, Al-Qahtani AM, Alshaybari K, Alshahrani M, Asaad AM.




Zika virus (ZIKV) is a teratogenic flavivirus that can cause microcephaly. Its main vector, Aedes aegypti, has been previ.ously identified in Saudi Arabia, but no ZIKV infection has yet been reported. Nevertheless, the country is at risk from ZIKV because it receives many travelers throughout the year, including pilgrims from ZIKV-endemic countries.


Screen asymptomatic pregnant mothers and their newborns attending a major hospital in the Najran region for subclinical or past infections with ZIKV, using ELISA and RT-PCR.




Najran Maternity and Children Hospital (NMCH).


All pregnant women admitted to NMCH in labor between November 2016 and July 2017 were included in the study. Clinical and demographic data were collected by pre-validated physician-administered questionnaires. Paired umbilical and maternal serum samples were collected and frozen at -60°C, using ELISA to measure anti-ZIKA IgG and IgM antibodies and RT-PCR to further investigate positive samples.


Maternal and newborn serum anti-ZIKV IgM and IgG and ZIKV RT-PCR.


410 mother-newborn pairs.


The median gestational age was 38.5 weeks (range 33-42). Most (n=342, 83.41%) of the women were from Najran city. All of the newborns had normal growth parameters with no congenital malformations. None of the mothers had symptoms suggestive of ZIKV infection; 3 (0.7%) exhibited a low-grade fever (38°C), but did not test positive for anti-ZIKV antibodies. Thirty-five (8.53%) of mothers had travelled inside Saudi Arabia, but none outside the country. Twenty-four (5.85%) mothers tested positive for anti-ZIKV IgM and 52 (12.68%) tested positive for anti-ZIKV IgG, but all infant samples were negative. All seropositive ZIKV IgM were also ZIKV IgG positive, but RT-PCR test.ing of all seropositive samples was negative.


Although previous (resolved) ZIKV infection and cross-reactivity of the ELISA method with other flaviviruses cannot be ex.cluded, the study found no confirmed cases of acute ZIKV infection. However, given the presence of the vector in Saudi Arabia, the presence of presumptive positive serology and the ongoing risk of ZIKV entry via a regular influx of travelers from endemic areas, we propose that continuous surveillance be conducted for ZIKV as well for other flaviviruses. Larger-scale nationwide studies are strongly recommended to gain a broader view of the potential threat from ZIKV in the country.


Small sample size, unavailability of plaque reduction neutralization tests to confirm serology results, and RT-PCR was only conducted on ELISA-positive serum samples, due to resource constraints.


PMID: 30531174 DOI: 10.5144/0256-4947.2018.408

Keywords: Saudi Arabia; Zika Virus; Zika Congenital Infection; Seroprevalence; Pregnancy.



Potential inconsistencies in [#Zika #surveillance data and our understanding of #risk during #pregnancy (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]


Potential inconsistencies in Zika surveillance data and our understanding of risk during pregnancy

James A. Hay, Pierre Nouvellet, Christl A. Donnelly, Steven Riley

Published: December 10, 2018 / DOI: https://doi.org/10.1371/journal.pntd.0006991 / This is an uncorrected proof.




A significant increase in microcephaly incidence was reported in Northeast Brazil at the end of 2015, which has since been attributed to an epidemic of Zika virus (ZIKV) infections earlier that year. Further incidence of congenital Zika syndrome (CZS) was expected following waves of ZIKV infection throughout Latin America; however, only modest increases in microcephaly and CZS incidence have since been observed. The quantitative relationship between ZIKV infection, gestational age and congenital outcome remains poorly understood.

Methodology/Principle findings

We characterised the gestational-age-varying risk of microcephaly given ZIKV infection using publicly available incidence data from multiple locations in Brazil and Colombia. We found that the relative timings and shapes of ZIKV infection and microcephaly incidence curves suggested different gestational risk profiles for different locations, varying in both the duration and magnitude of gestational risk. Data from Northeast Brazil suggested a narrow window of risk during the first trimester, whereas data from Colombia suggested persistent risk throughout pregnancy. We then used the model to estimate which combination of behavioural and reporting changes would have been sufficient to explain the absence of a second microcephaly incidence wave in Bahia, Brazil; a population for which we had two years of data. We found that a 18.9-fold increase in ZIKV infection reporting rate was consistent with observed patterns.


Our study illustrates how surveillance data may be used in principle to answer key questions in the absence of directed epidemiological studies. However, in this case, we suggest that currently available surveillance data are insufficient to accurately estimate the gestational-age-varying risk of microcephaly from ZIKV infection. The methods used here may be of use in future outbreaks and may help to inform improved surveillance and interpretation in countries yet to experience an outbreak of ZIKV infection.


Author summary

Zika virus (ZIKV) infection is associated with the rise of microcephaly cases observed in Northeast Brazil at the end of 2015. For women in endemic or at-risk areas, understanding how the relationship between time of infection and microcephaly risk varies through pregnancy is important in informing family planning. However, a relatively modest number of congenital Zika syndrome cases have been observed following subsequent waves of ZIKV infection, limiting our understanding of gestational risk. We used a mathematical model to quantify the shape and magnitude of the gestational-age-varying risk to a fetus. Although the risk profile should be conserved regardless of location, we estimated different profiles when using surveillance data from locations in Northeast Brazil and Colombia. Our results suggest that time-dependent reporting changes likely confound the interpretation of currently available surveillance data. Furthermore, we investigated a range of behavioural and reporting rate changes that could explain two waves of ZIKV infection in Bahia, Brazil despite only one wave of microcephaly. Plausible changes in reporting could explain these data whilst remaining consistent with the hypothesis that ZIKV infection carries a significant risk of microcephaly. Further evidence is needed to disentangle the true risk of congenital Zika syndrome from time-varying reporting changes.


Citation: Hay JA, Nouvellet P, Donnelly CA, Riley S (2018) Potential inconsistencies in Zika surveillance data and our understanding of risk during pregnancy. PLoS Negl Trop Dis 12(12): e0006991. https://doi.org/10.1371/journal.pntd.0006991

Editor: Ernesto T. A. Marques, University of Pittsburgh, UNITED STATES

Received: June 29, 2017; Accepted: November 12, 2018; Published: December 10, 2018

Copyright: © 2018 Hay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All files are available and embedded within the accompanying github repository https://github.com/jameshay218/zikaInfer.

Funding: For funding, we thank: The Wellcome Trust www.wellcome.ac.uk (Investigator Award, 200861/Z/16/Z, SR); The Medical Research Council, UK (www.mrc.ac.uk, JAH, SR, PN, CAD); National Institute for Health Research HPRU (SR, CAD, PN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Zika Virus; Zika Congenital infection; Pregnancy.


Sequential #Neuroimaging of the #Fetus and #Newborn With In Utero #Zika Virus Exposure (JAMA Pediatr., abstract)

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

JAMA Pediatr. 2018 Nov 26. doi: 10.1001/jamapediatrics.2018.4138. [Epub ahead of print]

Sequential Neuroimaging of the Fetus and Newborn With In Utero Zika Virus Exposure.

Mulkey SB1,2,3, Bulas DI4, Vezina G4, Fourzali Y5, Morales A5, Arroyave-Wessel M1, Swisher CB1, Cristante C1, Russo SM1, Encinales L6, Pacheco N7, Kousa YA8, Lanciotti RS9, Cure C10, DeBiasi RL2,11,12, du Plessis AJ1,2,3.

Author information: 1 Division of Fetal and Transitional Medicine, Children’s National Health System, Washington, DC. 2 Department of Pediatrics, School of Medicine and Health Sciences, The George Washington University, Washington, DC. 3 Department of Neurology, School of Medicine and Health Sciences, The George Washington University, Washington, DC. 4 Division of Radiology, Children’s National Health System, Washington, DC. 5 Sabbag Radiologos, Barranquilla, Colombia. 6 Allied Research Society, Miami, Florida. 7 Bacteriologa, Bio-Nep, Barranquilla, Colombia. 8 Division of Neurology, Children’s National Health System, Washington, DC. 9 Arbovirus Diseases Branch, Centers for Disease Control and Prevention, Fort Collins, Colorado. 10 BIOMELAB, Barranquilla, Colombia. 11 Division of Infectious Diseases, Children’s National Health System, Washington, DC. 12 Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC.




The evolution of fetal brain injury by Zika virus (ZIKV) infection is not well described.


To perform longitudinal neuroimaging of fetuses and infants exposed to in utero maternal ZIKV infection using concomitant magnetic resonance imaging (MRI) and ultrasonography (US), as well as to determine the duration of viremia in pregnant women with ZIKV infection and whether the duration of viremia correlated with fetal and/or infant brain abnormalities.


A cohort of 82 pregnant women with clinical criteria for probable ZIKV infection in Barranquilla, Colombia, and Washington, DC, were enrolled from June 15, 2016, through June 27, 2017, with Colombian women identified by community recruitment and physician referral and travel-related cases of American women recruited from a Congenital Zika Program.


Women received 1 or more MRI and US examinations during the second and/or third trimesters. Postnatally, infants underwent brain MRI and cranial US. Blood samples were tested for ZIKV.


The neuroimaging studies were evaluated for brain injury and cerebral biometry.


Of the 82 women, 80 were from Colombia and 2 were from the United States. In 3 of 82 cases (4%), fetal MRI demonstrated abnormalities consistent with congenital ZIKV infection. Two cases had heterotopias and malformations in cortical development and 1 case had a parietal encephalocele, Chiari II malformation, and microcephaly. In 1 case, US results remained normal despite fetal abnormalities detected on MRI. Prolonged maternal polymerase chain reaction positivity was present in 1 case. Of the remaining 79 cases with normal results of prenatal imaging, postnatal brain MRI was acquired in 53 infants and demonstrated mild abnormalities in 7 (13%). Fifty-seven infants underwent postnatal cranial US, which detected changes of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification in 21 infants (37%).


In a cohort of pregnant women with ZIKV infection, prenatal US examination appeared to detect all but 1 abnormal fetal case. Postnatal neuroimaging in infants who had normal prenatal imaging revealed new mild abnormalities. For most patients, prenatal and postnatal US may identify ZIKV-related brain injury.

PMID: 30476967 DOI: 10.1001/jamapediatrics.2018.4138

Keywords: Zika Virus; Zika Congenital Infection; Neurology.


Descriptive #report of cases of congenital syndrome associated with #Zika virus #infection in the state of São Paulo, #Brazil, from 2015 to 2017 (Epidemiol Serv Saude, abstract)

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

Epidemiol Serv Saude. 2018 Oct 22;27(3):e2017382. doi: 10.5123/S1679-49742018000300012.

Descriptive report of cases of congenital syndrome associated with Zika virus infection in the state of São Paulo, Brazil, from 2015 to 2017.

[Article in English, Portuguese; Abstract available in Portuguese from the publisher]

Martins RS1, Fróes MH1, Saad LDC1, Ignácio Junior SM1, Prado WDA1, Figueiredo EM1, Sato HK1, Ciccone FH1, Guimarães TC1, Katz G1.

Author information: 1 Secretaria de Estado da Saúde, Centro de Vigilância Epidemiológica Professor Alexandre Vranjac, São Paulo, SP, Brasil.


Abstract in English, Portuguese, Spanish


to characterize cases of congenital syndrome associated with Zika virus infection (CZS) and other infectious etiologies, resident in the state of São Paulo, Brazil, from October 30, 2015, to June 30, 2017.


this was a descriptive study of suspected cases of CZS and other infectious etiologies notified on the Public Health Events Registry.


960 cases were investigated up to epidemiological week 26/2017, and 146 were confirmed for congenital infection; of these, 59 (40.4%) were confirmed for congenital infection without etiological identification and 87 (59.6%) with laboratory confirmation, of which 55 were congenital syndrome associated with Zika virus and 32 were congenital syndrome associated with other infectious agents.


this study enabled the detection of 23.9% CZS cases among suspected cases of infectious etiology.

PMID: 30365699 DOI: 10.5123/S1679-49742018000300012

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


Review: #Evidence of #Neurological #Sequelae in #Children With Acquired #Zika Virus #Infection (Pediatr Neurol., abstract)

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

Pediatr Neurol. 2018 Aug;85:16-20. doi: 10.1016/j.pediatrneurol.2018.03.001. Epub 2018 Apr 3.

Review: Evidence of Neurological Sequelae in Children With Acquired Zika Virus Infection.

Lebov JF1, Brown LM2, MacDonald PDM3, Robertson K4, Bowman NM5, Hooper SR6, Becker-Dreps S7.

Author information: 1 RTI International, Center for Applied Public Health Research, Durham, North Carolina. Electronic address: jlebov@rti.org. 2 RTI International, Center for Applied Public Health Research, Rockville, Maryland. 3 RTI International, Center for Applied Public Health Research, Berkeley, California. 4 Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina. 5 Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina. 6 Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina. 7 Department of Family Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.



Limited information is available on health outcomes related to Zika virus infection acquired during childhood. Zika virus can cause severe central nervous system malformations in congenitally exposed fetuses and neonates. In vitro studies show the capacity of Zika virus to infect neural progenitor cells, induce central and peripheral neuronal cell deaths, and target different brain cells over the course of brain development. Studies of postnatally infected mice and nonhuman primates have detected degradation of neural cells and morphologic brain cell changes consistent with a broad neuroinflammatory response. In addition, case reports of central nervous system disease in adults and in adolescents secondary to Zika virus infection suggest that Zika virus may have a broader impact on neurological health beyond that observed in congenitally exposed newborns. Long-term neurological complications have been observed with other acquired flaviviral infections, with clinical symptoms manifesting for years after primary infection. The extent to which postnatal Zika virus infection in humans negatively affects the central and peripheral nervous systems and causes long-term neurological damage or cognitive effects is currently unknown. To better understand the potential for neurological sequelae associated with acquired Zika virus infection in children, we reviewed the biological, clinical, and epidemiologic literature and summarized the evidence for this link. First, we review biological mechanisms for neurological manifestations of Zika virus infection in experimental studies. Second, we review observational studies of congenital Zika virus infection and case studies and surveillance reports of neurological sequelae of Zika virus infection in adults and in children. Lastly, we discuss the challenges of conducting Zika virus-neurological sequela studies and future directions for pediatric Zika virus research.

KEYWORDS: Child development; Flavivirus infections; Malformations of cortical development; Neurological sequelae; Zika virus infection

PMID: 30343688 DOI: 10.1016/j.pediatrneurol.2018.03.001

Keywords: Zika Virus; Zika Congenital Syndrome; Neurology.


Association and #birth #prevalence of #microcephaly attributable to #Zika virus infection among #infants in Paraíba, #Brazil, in 2015-16: a case-control study (Lancet Child Adolesc Health, abstract)

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

Lancet Child Adolesc Health. 2018 Mar;2(3):205-213. doi: 10.1016/S2352-4642(18)30020-8. Epub 2018 Jan 12.

Association and birth prevalence of microcephaly attributable to Zika virus infection among infants in Paraíba, Brazil, in 2015-16: a case-control study.

Krow-Lucal ER1, de Andrade MR2, Cananéa JNA3, Moore CA4, Leite PL5, Biggerstaff BJ6, Cabral CM2, Itoh M7, Percio J8, Wada MY8, Powers AM6, Barbosa A9, Abath RB3, Staples JE6, Coelho GE5; Paraíba Microcephaly Work Group.

Collaborators (38): Araújo E, Medeiros ELA, Brant J, Cerroni M, de Barros Moreira Beltrão H, Fantinato FFST, Lise MLZ, Ohara PM, Resende E, Saad E, de St Maurice A, Dieke A, Harrist A, Kwit N, Marlow M, Soke G, de Arruda Pessoa R, da Silva RC, Diniz RC, de Araújo Ariette MC, Lira CF, Matos S, Wanderley TMM, Silva VOC, da Silva HS, Carmo EH, Carvalho M, Lentini N, Miranda R, Boland E, Burns P, Fischer M, Ledermann J, Coronado F, Dicent-Taillepierre J, Flannery B, Macedo de Oliveira A, Arena JF.

Author information: 1 Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, USA; EIS Program Office, Centers for Disease Control and Prevention, Atlanta, GA, USA. 2 Epidemiologia Aplicada aos Serviços do Sistema Único de Saúde (Episus), Brasilia, Brazil. 3 Secretariat of Health, Paraíba, Brazil. 4 Division of Congenital and Developmental Disorders, Centers for Disease Control and Prevention, Atlanta, GA, USA. 5 National Dengue Control Program, Brazil Ministry of Health, Brasilia, Brazil. 6 Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, USA. 7 EIS Program Office, Centers for Disease Control and Prevention, Atlanta, GA, USA. 8 Epidemiologia Aplicada aos Serviços do Sistema Único de Saúde (Episus), Brasilia, Brazil; National Dengue Control Program, Brazil Ministry of Health, Brasilia, Brazil. 9 Brazil Country Office, Centers for Disease Control and Prevention, Brasilia, Brazil.




In 2015, the number of infants born with microcephaly increased in Paraíba, Brazil, after a suspected Zika virus outbreak. We did a retrospective case-control investigation to assess the association of microcephaly and Zika virus.


We enrolled cases reported to the national database for microcephaly and born between Aug 1, 2015, and Feb 1, 2016, on the basis of their birth head circumference and total body length. We identified controls from the national birth registry and matched them to cases by location, aiming to enrol a minimum of two controls per case. Mothers of both cases and controls were asked about demographics, exposures, and illnesses and infants were measured at a follow-up visit 1-7 months after birth. We took blood samples from mothers and infants and classified those containing Zika virus IgM and neutralising antibodies as evidence of recent infection. We calculated prevalence of microcephaly and odds ratios (ORs) using a conditional logistic regression model with maximum penalised conditional likelihood, and combined these ORs with exposure probability estimates to determine the attributable risk.


We enrolled 164 of 706 infants with complete information reported with microcephaly at birth, of whom we classified 91 (55%) as having microcephaly on the basis of their birth measurements, 36 (22%) as small, 21 (13%) as disproportionate, and 16 (10%) as not having microcephaly. 43 (26%) of the 164 infants had microcephaly at follow-up for an estimated prevalence of 5·9 per 1000 livebirths. We enrolled 114 control infants matched to the 43 infants classified as having microcephaly at follow-up. Infants with microcephaly at follow-up were more likely than control infants to be younger (OR 0·5, 95% CI 0·4-0·7), have recent Zika virus infection (21·9, 7·0-109·3), or a mother with Zika-like symptoms in the first trimester (6·2, 2·8-15·4). Once Zika virus infection and infant age were controlled for, we found no significant association between microcephaly and maternal demographics, medications, toxins, or other infections. Based on the presence of Zika virus antibodies in infants, we concluded that 35-87% of microcephaly occurring during the time of our investigation in northeast Brazil was attributable to Zika virus. We estimate 2-5 infants per 1000 livebirths in Paraíba had microcephaly attributable to Zika virus.


Time of exposure to Zika virus and evidence of infection in the infants were the only risk factors associated with microcephaly. This investigation has improved understanding of the outbreak of microcephaly in northeast Brazil and highlights the need to obtain multiple measurements after birth to establish if an infant has microcephaly and the need for further research to optimise testing criteria for congenital Zika virus infection.


Centers for Disease Control and Prevention.

Copyright © 2018 Elsevier Ltd. All rights reserved.

PMID: 30169255 DOI: 10.1016/S2352-4642(18)30020-8

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


The emergence of #Zika virus and its new #clinical #syndromes (Nature, abstract)

[Source: Nature, full page: (LINK). Abstract, edited.]

The emergence of Zika virus and its new clinical syndromes

Theodore C. Pierson &  Michael S. Diamond

Nature, volume 560, pages573–581 (2018)



Zika virus (ZIKV) is a mosquito-transmitted flavivirus that has emerged as a global health threat because of its potential to generate explosive epidemics and ability to cause congenital disease in the context of infection during pregnancy. Whereas much is known about the biology of related flaviviruses, the unique features of ZIKV pathogenesis, including infection of the fetus, persistence in immune-privileged sites and sexual transmission, have presented new challenges. The rapid development of cell culture and animal models has facilitated a new appreciation of ZIKV biology. This knowledge has created opportunities for the development of countermeasures, including multiple ZIKV vaccine candidates, which are advancing through clinical trials. Here we describe the recent advances that have led to a new understanding of the causes and consequences of the ZIKV epidemic.

Keywords: Zika Virus; Zika Congenital Syndrome.