Zika Virus Infections in Pregnancy and Congenital Zika Syndrome in the Latin American Region

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 59739

Special Issue Editors


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Guest Editor
London School of Hygiene & Tropical Medicine, London, UK
Interests: neglected tropical diseases; vector-borne diseases; congenital infection; health equity; epidemic preparedness; vaccines

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Guest Editor
Aggeu Magalhães Institute, Oswaldo Cruz Foundation (FIOCRUZ), Recife, Pernambuco, Brazil
Interests: epidemiology of infectious diseases; vector-borne diseases; congenital infection; outbreak investigation

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Guest Editor
Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
Interests: emerging infectious diseases; global maternal & child health; tropical medicine; pregnancy complications; maternal and infant mortality; epidemiology; medical anthropology; obstetrical pathology
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Special Issue Information

Dear Colleagues,

At the 3rd International Conference on Zika Virus and Aedes Related Infections held in Washington DC, 13–16 February 2020, it was agreed to prepare a Special Issue of Viruses incorporating the latest information on the public health problems of Zika virus (ZIKV) infection among pregnant women and their infants in the Latin American region. Following recognition of the teratogenic potential of ZIKV in 2015, studies have been conducted to understand the risks of prenatal exposure to ZIKV, describe the spectrum of birth defects and functional disabilities arising from congenital ZIKV infections, define the prognosis for children with congenital Zika syndrome, and address the sociocultural aspects of the infection on affected families.

The editors of this Special Issue, “Zika Virus Infections in Pregnancy and Congenital Zika Syndrome in the Latin American Region”, cordially invite your participation. This topical Issue of Viruses welcomes contributions dealing with all aspects of Zika virus infection in pregnancy and infancy, including original research articles, systematic literature reviews, commentaries, case reports, and perspective pieces. Topics include biomedical, laboratory, epidemiological, diagnostic, virological, and anthropological and social science aspects of the topic. Authors from regions endemic for Zika virus are encouraged to participate in this Issue.

Dr. Elizabeth B. Brickley
Prof. Dr. Celina M.T. Martelli
Prof. Dr. David A. Schwartz
Guest Editors

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Keywords

  • arbovirus
  • Zika virus
  • pregnancy
  • congenital infection
  • congenital Zika syndrome
  • microcephaly
  • birth defects
  • maternal health
  • infant health

Published Papers (22 papers)

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14 pages, 812 KiB  
Article
High Incidence of Zika or Chikungunya Infection among Pregnant Women Hospitalized Due to Obstetrical Complications in Northeastern Brazil—Implications for Laboratory Screening in Arbovirus Endemic Area
by Iracema J. A. A. Jacques, Leila Katz, Marília A. Sena, Ana B. G. Guimarães, Yasmim L. Silva, Gabriela D. M. Albuquerque, Raisa O. Pereira, Camila A. M. C. de Albuquerque, Maria Almerice L. Silva, Paula A. S. Oliveira, Maria de Fátima P. M. Albuquerque, Marli T. Cordeiro, Ernesto T. A. Marques, Jr., Rafael F. O. França, Celina M. T. Martelli, Priscila M. S. Castanha and Cynthia Braga
Viruses 2021, 13(5), 744; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050744 - 23 Apr 2021
Cited by 6 | Viewed by 2124
Abstract
The diagnostic of arbovirus-related obstetric complications in high-risk pregnancy and childbirth care is challenging, especially in endemic areas. We conducted a prospective study to track active or recent Zika (ZIKV), dengue (DENV), or chikungunya (CHIKV) virus infection among hospitalized pregnant women (PW) with [...] Read more.
The diagnostic of arbovirus-related obstetric complications in high-risk pregnancy and childbirth care is challenging, especially in endemic areas. We conducted a prospective study to track active or recent Zika (ZIKV), dengue (DENV), or chikungunya (CHIKV) virus infection among hospitalized pregnant women (PW) with obstetric complications in a hospital at the epicenter of Zika outbreak and ZIKV-related microcephaly in Brazil. Clinical data and blood samples were collected at enrollment and 10 days after the admission of study participants, between October 2018 and May 2019. Further clinical data were extracted from medical records. Samples were screened by molecular and serological tests. Out of 780 participants, 93.1% (95% CI: 91.1–94.7%) presented previous DENV exposure (IgG). ZIKV, CHIKV, and/or DENV laboratory markers of recent or active infection were detected in 130 PW, yielding a prevalence of 16.6% (95% CI: 14.2–19.5%); 9.4% (95% CI: 7.4–11.7%), 7.4% (95% CI: 5.7–9.7%), and 0.38% (95% CI: 0.1–1.2%) of CHIKV, ZIKV, and DENV infections, respectively. Most ZIKV infections were detected by molecular assays (89.6%), while CHIKV infections were detected by serology (95.9%). Our findings highlight the need for arbovirus infections screening in PW with obstetrical complications, potentially associated to these infections in endemic areas regardless of the signs or symptoms suggestive of arboviral disease. Full article
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12 pages, 749 KiB  
Article
Why Did ZIKV Perinatal Outcomes Differ in Distinct Regions of Brazil? An Exploratory Study of Two Cohorts
by Luana Damasceno, Ana Carolina B. Terzian, Trevon Fuller, Cassia F. Estofolete, Adriana Andrade, Erna G. Kroon, Andrea A. Zin, Zilton Vasconcelos, Jose P. Pereira, Jr., Márcia C. Castilho, Isa Cristina R. Piaulino, Nikos Vasilakis, Maria E. Moreira, Karin Nielsen-Saines, Flor E. Martinez Espinosa, Maurício L. Nogueira and Patricia Brasil
Viruses 2021, 13(5), 736; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050736 - 23 Apr 2021
Cited by 5 | Viewed by 3541
Abstract
The Zika virus (ZIKV) epidemic in Brazil occurred in regions where dengue viruses (DENV) are historically endemic. We investigated the differences in adverse pregnancy/infant outcomes in two cohorts comprising 114 pregnant women with PCR-confirmed ZIKV infection in Rio de Janeiro, Southeastern Brazil ( [...] Read more.
The Zika virus (ZIKV) epidemic in Brazil occurred in regions where dengue viruses (DENV) are historically endemic. We investigated the differences in adverse pregnancy/infant outcomes in two cohorts comprising 114 pregnant women with PCR-confirmed ZIKV infection in Rio de Janeiro, Southeastern Brazil (n = 50) and Manaus, in the north region of the country (n = 64). Prior exposure to DENV was evaluated through plaque reduction neutralizing antibody assays (PRNT 80) and DENV IgG serologies. Potential associations between pregnancy outcomes and Zika attack rates in the two cities were explored. Overall, 31 women (27%) had adverse pregnancy/infant outcomes, 27 in Rio (54%) and 4 in Manaus (6%), p < 0.001. This included 4 pregnancy losses (13%) and 27 infants with abnormalities at birth (24%). A total of 93 women (82%) had evidence of prior DENV exposure, 45 in Rio (90%) and 48 in Manaus (75%). Zika attack rates differed; the rate in Rio was 10.28 cases/10,000 and in Manaus, 0.6 cases/10,000, p < 0.001. Only Zika attack rates (Odds Ratio: 17.6, 95% Confidence Interval 5.6–55.9, p < 0.001) and infection in the first trimester of pregnancy (OR: 4.26, 95% CI 1.4–12.9, p = 0.011) were associated with adverse pregnancy and infant outcomes. Pre-existing immunity to DENV was not associated with outcomes (normal or abnormal) in patients with ZIKV infection during pregnancy. Full article
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10 pages, 3267 KiB  
Article
Persistence of Anti-ZIKV-IgG over Time Is Not a Useful Congenital Infection Marker in Infants Born to ZIKV-Infected Mothers: The NATZIG Cohort
by Conrado Milani Coutinho, Juliana Dias Crivelenti Pereira Fernandes, Aparecida Yulie Yamamoto, Silvia Fabiana Biason de Moura Negrini, Bento Vidal de Moura Negrini, Sara Reis Teixeira, Fabiana Rezende Amaral, Márcia Soares Freitas da Motta, Adriana Aparecida Tiraboschi Bárbaro, Davi Casale Aragon, Magelda Montoya, Eva Harris, Geraldo Duarte, Marisa Márcia Mussi-Pinhata and for the NATZIG Cohort Study Team
Viruses 2021, 13(4), 711; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040711 - 20 Apr 2021
Cited by 3 | Viewed by 2029
Abstract
Confirming ZIKV congenital infection is challenging because viral RNA is infrequently detected. We compared the presence of anti-ZIKV-IgM and the persistence of anti-ZIKV-IgG antibodies over 18 months in two cohorts of infants born to ZIKV-infected mothers: Cohort one: 30 infants with typical microcephaly [...] Read more.
Confirming ZIKV congenital infection is challenging because viral RNA is infrequently detected. We compared the presence of anti-ZIKV-IgM and the persistence of anti-ZIKV-IgG antibodies over 18 months in two cohorts of infants born to ZIKV-infected mothers: Cohort one: 30 infants with typical microcephaly or major brain abnormalities (Congenital Zika Syndrome-CZS); Cohort two: 123 asymptomatic infants. Serum samples obtained within 6 months of age were tested for anti-ZIKV-IgM. Anti-ZIKV-IgG was quantified in sequential samples collected at birth, 3–6 weeks, 3, 6, 12, and 18 months. ZIKV-RNA was never detected postnatally. Anti-ZIKV-IgM antibodies were detected at least once in 15/25 (60.0%; 95%CI: 38.7–78.9) infants with CZS and in 2/115 (1.7%; 95%CI: 0.2–6.1) asymptomatic infants. Although anti-ZIKV-IgG was always positive within 3–6 weeks of age, IgG levels decreased similarly over time in both cohorts. IgG levels decreased similarly in ZIKV-IgM-positive and ZIKV-IgM-negative CZS infants. Differently from other congenital infections, IgM would fail to diagnose 40% of severely symptomatic infants, and the persistence of IgG is not a useful marker for discriminating congenital infection among infants exposed to maternal ZIKV infection. Full article
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11 pages, 471 KiB  
Article
Hematological Profile of Pregnant Women with Suspected Zika Virus Infection Followed Up at a Referral Service in Manaus, Brazil
by Anny Beatriz Costa Antony de Andrade, Maria Jacirema Ferreira Gonçalves, Elijane de Fátima Redivo, Maria das Graças Costa Alecrim and Flor Ernestina Martinez-Espinosa
Viruses 2021, 13(4), 710; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040710 - 20 Apr 2021
Cited by 2 | Viewed by 1883
Abstract
The purpose of this paper is to describe the hematological profile of pregnant women with suspected Zika virus (ZIKV) infection followed up at a reference service for infectious diseases in Manaus, Brazil, through a clinical, epidemiological, cross-sectional study of pregnant women with an [...] Read more.
The purpose of this paper is to describe the hematological profile of pregnant women with suspected Zika virus (ZIKV) infection followed up at a reference service for infectious diseases in Manaus, Brazil, through a clinical, epidemiological, cross-sectional study of pregnant women with an exanthematic manifestation who looked for care between 2015 and 2017. The participants were 499 pregnant women, classified into four subgroups, according to laboratory confirmation of infections: ZIKV-positive; ZIKV-positive and positive for another infection; positive for another infection but not ZIKV-positive; and not positive for any of the infections investigated. Hematological parameters were analyzed descriptively. The association between maternal infection and the hematological profile, along with the association between the maternal hematological profile and the gestational outcome, were tested. Similar hematic and platelet parameters were observed among pregnant women. However, a significant association was observed between low maternal lymphocyte count and a positive diagnosis for ZIKV (p < 0.001). The increase in maternal platelet count and the occurrence of unfavorable gestational outcome were positively associated. A similar hematic and platelet profile was identified among pregnant women, differing only in the low lymphocyte count among ZIKV-positive pregnant women. Regarding gestational outcomes, in addition to the damage caused by ZIKV infection, altered maternal platelets may lead to unfavorable outcomes, with the need for adequate follow-up during prenatal care. Full article
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15 pages, 2938 KiB  
Article
The Microcephaly Epidemic Research Group Paediatric Cohort (MERG–PC): A Cohort Profile
by Demócrito de Barros Miranda-Filho, Elizabeth B. Brickley, Anna Ramond, Celina Maria Turchi Martelli, Nuria Sanchez Clemente, Thália Velho Barreto de Araújo, Laura Cunha Rodrigues, Ulisses Ramos Montarroyos, Wayner Vieira de Souza, Maria de Fátima P. M. de Albuquerque, Liana O. Ventura, Ernesto T. A. Marques, Mariana C. Leal, Sophie H. Eickmann, Maria Angela Wanderley Rocha, Paula Fabiana Sobral da Silva, Maria Durce Costa Gomes Carvalho, Regina Coeli F. Ramos, Danielle Maria da Silva Oliveira, Morgana do Nascimento Xavier, Rômulo A. L. Vasconcelos, Andreia Veras Gonçalves, Alessandra Mertens Brainer, Marli Tenório Cordeiro, Ricardo Arraes de Alencar Ximenes and on behalf of the Microcephaly Epidemic Research Groupadd Show full author list remove Hide full author list
Viruses 2021, 13(4), 602; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040602 - 01 Apr 2021
Cited by 5 | Viewed by 2628
Abstract
This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG–PC). The profile details the context and aims of the study, study population, methodology including assessments, and key results and publications to date. The [...] Read more.
This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG–PC). The profile details the context and aims of the study, study population, methodology including assessments, and key results and publications to date. The children that make up MERG–PC were born in Recife or within 120 km of the city, in Pernambuco/Brazil, the epicentre of the microcephaly epidemic. MERG–PC includes children from four groups recruited at different stages of the ZIKV microcephaly epidemic in Pernambuco, i.e., the Outpatient Group (OG/n = 195), the Microcephaly Case–Control Study (MCCS/n = 80), the MERG Pregnant Women Cohort (MERG-PWC/n = 336), and the Control Group (CG/n = 100). We developed a comprehensive array of clinical, laboratory, and imaging assessments that were undertaken by a ‘task force’ of clinical specialists in a single day at 3, 6, 12, 18 months of age, and annually from 24 months. Children from MCCS and CG had their baseline assessment at birth and children from the other groups, at the first evaluation by the task force. The baseline cohort includes 711 children born between February 2015 and February 2019. Children’s characteristics at baseline, excluding CG, were as follows: 32.6% (184/565) had microcephaly, 47% (263/559) had at least one physical abnormality, 29.5% (160/543) had at least one neurological abnormality, and 46.2% (257/556) had at least one ophthalmological abnormality. This ongoing cohort has contributed to the understanding of the congenital Zika syndrome (CZS) spectrum. The cohort has provided descriptions of paediatric neurodevelopment and early epilepsy, including EEG patterns and treatment response, and information on the frequency and characteristics of oropharyngeal dysphagia; cryptorchidism and its surgical findings; endocrine dysfunction; and adenoid hypertrophy in children with Zika-related microcephaly. The study protocols and questionnaires were shared across Brazilian states to enable harmonization across the different studies investigating microcephaly and CZS, providing the opportunity for the Zika Brazilian Cohorts Consortium to be formed, uniting all the ZIKV clinical cohorts in Brazil. Full article
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15 pages, 840 KiB  
Article
Three-Year Clinical Follow-Up of Children Intrauterine Exposed to Zika Virus
by Rosa Estela Gazeta, Ana Paula Antunes Pascalicchio Bertozzi, Rita de Cássia de Aguirre Bernardes Dezena, Andrea Cristina Botelho Silva, Thamirys Cosmo Gillo Fajardo, Daniel T. Catalan, Maria de Fátima Valente Rizzo, Antonio Fernandes Moron, Antoni Soriano-Arandes, Nuria Sanchez Clemente, Tania Quintella, Dora Fix Ventura, Francisco Max Damico, Valtenice de Cassia Rodrigues de Matos França, Juliana Paula Gomes de Almeida, Ana Laura de Sene Amâncio Zara, Lucas Castro Pires, Cohort Zika vírus Jundiaí and Saulo Duarte Passos
Viruses 2021, 13(3), 523; https://0-doi-org.brum.beds.ac.uk/10.3390/v13030523 - 22 Mar 2021
Cited by 11 | Viewed by 3274
Abstract
Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women [...] Read more.
Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women and/or newborns were considered ZIKV exposed and/or infected. Laboratory diagnosis was made by polymerase chain reaction in the pregnant mothers and their respective newborns, as well as Dengue virus, Chikungunya virus, and ZIKV serology. Serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis infections were also performed in microcephalic newborns. The newborns included in the study were followed up until their third birthday. Developmental delay was observed in nine patients (13.2%): mild cognitive delay in three patients, speech delay in three patients, autism spectrum disorder in two patients, and severe neurological abnormalities in one microcephalic patient; sensorineural hearing loss, three patients and dysphagia, six patients. Microcephaly due to ZIKV occurred in three patients (3.6%). Clinical manifestations can appear after the first year of life in children infected/exposed to ZIKV, emphasizing the need for long-term follow-up. Full article
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13 pages, 780 KiB  
Article
Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly
by Julia A. Gomes, Eduarda Sgarioni, Juliano A. Boquett, Ana Cláudia P. Terças-Trettel, Juliana H. da Silva, Bethânia F. R. Ribeiro, Marcial F. Galera, Thalita M. de Oliveira, Maria Denise F. Carvalho de Andrade, Isabella F. Carvalho, Lavínia Schüler-Faccini and Fernanda S. L. Vianna
Viruses 2021, 13(2), 325; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020325 - 20 Feb 2021
Cited by 7 | Viewed by 2218
Abstract
Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to [...] Read more.
Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly. Full article
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9 pages, 637 KiB  
Article
Knowledge of Zika Virus Transmission and Its Prevention among High-Risk Pregnant Women in Brazil
by Lucas C. Pires, Luiza R. Dantas, Steven S. Witkin, Ana Paula A. P. Bertozzi, Rita de Cássia A. B. Dezena, Maria M. D. Rodrigues, Rosa Estela Gazeta and Saulo D. Passos
Viruses 2021, 13(2), 242; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020242 - 04 Feb 2021
Cited by 5 | Viewed by 2991
Abstract
Recent outbreaks of Zika virus (ZIKV) infection highlight the urgent need to evaluate the efficacy of current public health measures to educate susceptible groups about how to prevent infection, modes of viral transmission, and consequences of infection. We performed a cross-sectional study in [...] Read more.
Recent outbreaks of Zika virus (ZIKV) infection highlight the urgent need to evaluate the efficacy of current public health measures to educate susceptible groups about how to prevent infection, modes of viral transmission, and consequences of infection. We performed a cross-sectional study in the city of Jundiaí, São-Paulo, from March 2016 to August 2017. In 315 high-risk pregnant women we evaluated the rate of ZIKV infection, knowledge of pathways of ZIKV transmission, and the use of protective measures. Data were analyzed and correlated with sociodemographic variables. The rate of ZIKV infection was 10.8%. ZIKV transmission by mosquitoes was the best-known means of virus acquisition, while transmission of ZIKV by sexual intercourse as well as mother–fetus transmission was known by less than half of the women. The use of insect repellent, reported by 53% of participants, was correlated with higher education and personal directives from health professionals. Condom use was reported by 19.5% of subjects. Improved strategies to increase awareness of ZIKV infection and its consequences, designed to appeal to specific, targeted populations, are clearly necessary to more accurately prevent the spread of this infection and diminish adverse consequences in the pregnant population. Full article
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18 pages, 1497 KiB  
Article
Evaluation of the Expression of CCR5 and CX3CR1 Receptors and Correlation with the Functionality of T Cells in Women infected with ZIKV during Pregnancy
by Débora Familiar-Macedo, Iury Amancio Paiva, Jessica Badolato-Corrêa da Silva, Fabiana Rabe de Carvalho, Helver Gonçalves Dias, Alex Pauvolid-Corrêa, Caroline Fernandes dos Santos, Mariana Gandini, Andréa Alice Silva, Silvia Maria Baeta Cavalcanti, Solange Artimos de Oliveira, Renata Artimos de Oliveira Vianna, Elzinandes Leal de Azeredo, Alba Grifoni, Alessandro Sette, Daniela Weiskopf, Claudete Aparecida Araújo Cardoso and Luzia Maria de-Oliveira-Pinto
Viruses 2021, 13(2), 191; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020191 - 28 Jan 2021
Cited by 2 | Viewed by 2477
Abstract
There have been reports of neurological abnormalities associated with the Zika virus (ZIKV), such as congenital Zika syndrome (CZS) in children born to mothers infected during pregnancy. We investigated how the immune response to ZIKV during pregnancy is primed and conduct a thorough [...] Read more.
There have been reports of neurological abnormalities associated with the Zika virus (ZIKV), such as congenital Zika syndrome (CZS) in children born to mothers infected during pregnancy. We investigated how the immune response to ZIKV during pregnancy is primed and conduct a thorough evaluation of the inflammatory and cytotoxic profiles as well as the expression of CCR5 and CX3CR1. We compared the reactivity of T cells to ZIKV peptides in convalescent mothers infected during pregnancy. The child’s clinical outcome (i.e., born with or without CZS) was taken to be the variable. The cells were stimulated in vitro with ZIKV peptides and evaluated using the ELISPOT and flow cytometry assays. After in vitro stimulation with ZIKV peptides, we observed a tendency toward a higher Interferon gamma (IFN-γ)-producing T cell responses in mothers who had asymptomatic children and a higher CD107a expression in T cells in mothers who had children with CZS. We found a higher frequency of T cells expressing CD107a+ and co-expressing CX3CR1+CCR5+, which is much clearer in the T cells of mothers who had CZS children. We suggest that this differential profile influenced the clinical outcome of babies. These data need to be further investigated, including the evaluation of other ZIKV peptides and markers and functional assays. Full article
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9 pages, 722 KiB  
Article
The Prevalence of Adenoid Hypertrophy among Children with Zika Related Microcephaly
by Mariana C. Leal, Danielle Seabra Ramos, Thiago Pinto Bezerra, Ana Elizabeth S. C. Vilela, Rebeka Jacques de F. Maciel, Mirella Rodrigues, Mariana Lira, Karen Pena de Souza Cavalcanti, Vanessa Van der Linden, Marli T. Cordeiro, Demócrito Miranda-Filho, Ricardo Ximenes, Elizabeth B. Brickley and Silvio S. Caldas
Viruses 2021, 13(1), 62; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010062 - 05 Jan 2021
Cited by 12 | Viewed by 3339
Abstract
Upper respiratory obstruction is a common sequela in children with Zika-related microcephaly (ZRM). As a cross-sectional analysis nested in a cohort study, this study aims to investigate the prevalence of adenoid hypertrophy (AH) in children with ZRM and symptoms of respiratory obstruction. The [...] Read more.
Upper respiratory obstruction is a common sequela in children with Zika-related microcephaly (ZRM). As a cross-sectional analysis nested in a cohort study, this study aims to investigate the prevalence of adenoid hypertrophy (AH) in children with ZRM and symptoms of respiratory obstruction. The data were collected in the first three years of life from children with ZRM who were followed in two reference centers for otorhinolaryngological care of patients with congenital Zika syndrome. Out of 92 children with confirmed ZRM, 57 were evaluated by nasopharyngoscopy after presenting with upper respiratory obstruction symptoms. In this study, 31 of the 57 (54%) children with ZRM who were evaluated had obstructive AH. Thirteen children with obstructive AH were submitted to surgery, which resulted in the complete resolution of symptoms for 11, partial resolution in 1, and no improvement in 1. No evidence of direct involvement by Zika virus (ZIKV) infection in the adenoid tissues was demonstrated by histology or immunohistochemistry. Our results suggest that there is a high prevalence and early presentation of AH in children with ZRM, with consequent upper airway obstruction causing upper airway obstructive disorder, secretory otitis media, and dysphagia. Full article
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11 pages, 6189 KiB  
Article
New Insights on the Zika Virus Arrival in the Americas and Spatiotemporal Reconstruction of the Epidemic Dynamics in Brazil
by Larissa Catharina Costa, Rafael Valente Veiga, Juliane Fonseca Oliveira, Moreno S. Rodrigues, Roberto F. S. Andrade, Enny S. Paixão, Maria Glória Teixeira, Maria da Conceição N. Costa, Luciana L. Cardim, Eduardo H. Carmo, Wanderson K. Oliveira, José Í. K. Gonçalves, Qeren H. R. F. Fernandes, Maurício L. Barreto, Artur T. L. Queiroz and Tiago Gräf
Viruses 2021, 13(1), 12; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010012 - 23 Dec 2020
Cited by 8 | Viewed by 3220
Abstract
Zika virus (ZIKV) became a worldwide public health emergency after its introduction in the Americas. Brazil was implicated as central in the ZIKV dispersion, however, a better understanding of the pathways the virus took to arrive in Brazil and the dispersion within the [...] Read more.
Zika virus (ZIKV) became a worldwide public health emergency after its introduction in the Americas. Brazil was implicated as central in the ZIKV dispersion, however, a better understanding of the pathways the virus took to arrive in Brazil and the dispersion within the country is needed. An updated genome dataset was assembled with publicly available data. Bayesian phylogeography methods were applied to reconstruct the spatiotemporal history of ZIKV in the Americas and with more detail inside Brazil. Our analyses reconstructed the Brazilian state of Pernambuco as the likely point of introduction of ZIKV in Brazil, possibly during the 2013 Confederations Cup. Pernambuco played an important role in spreading the virus to other Brazilian states. Our results also underscore the long cryptic circulation of ZIKV in all analyzed locations in Brazil. Conclusions: This study brings new insights about the early moments of ZIKV in the Americas, especially regarding the Brazil-Haiti cluster at the base of the American clade and describing for the first time migration patterns within Brazil. Full article
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13 pages, 302 KiB  
Article
Endocrine Dysfunction in Children with Zika-Related Microcephaly Who Were Born during the 2015 Epidemic in the State of Pernambuco, Brazil
by Andréia Veras Gonçalves, Demócrito de B. Miranda-Filho, Líbia Cristina Rocha Vilela, Regina Coeli Ferreira Ramos, Thalia V. B. de Araújo, Rômulo A. L. de Vasconcelos, Maria Angela Wanderley Rocha, Sophie Helena Eickmann, Marli Tenório Cordeiro, Liana O. Ventura, Ulisses Ramos Montarroyos, Alessandra Mertens Brainer, Maria Durce Costa Gomes, Paula Fabiana Sobral da Silva, Celina M. T. Martelli, Elizabeth B. Brickley and Ricardo A. A. Ximenes
Viruses 2021, 13(1), 1; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010001 - 22 Dec 2020
Cited by 10 | Viewed by 2719
Abstract
Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case [...] Read more.
Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common—and clinically important—endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary. Full article
16 pages, 317 KiB  
Article
“Life Is Taking Me Where I Need to Go”: Biographical Disruption and New Arrangements in the Lives of Female Family Carers of Children with Congenital Zika Syndrome in Pernambuco, Brazil
by Ana Paula Lopes de Melo, Tereza Lyra, Thália Velho Barreto de Araújo, Maria do Socorro Veloso de Albuquerque, Sandra Valongueiro, Hannah Kuper and Loveday Penn-Kekana
Viruses 2020, 12(12), 1410; https://0-doi-org.brum.beds.ac.uk/10.3390/v12121410 - 08 Dec 2020
Cited by 7 | Viewed by 2208
Abstract
The congenital Zika syndrome (CZS) epidemic in Brazil turned the spotlight on many other factors beyond illness, such as poverty, gender, and inequalities in health care. Women were the emblematic subjects in this study, not only because Zika virus is a vertical transmission [...] Read more.
The congenital Zika syndrome (CZS) epidemic in Brazil turned the spotlight on many other factors beyond illness, such as poverty, gender, and inequalities in health care. Women were the emblematic subjects in this study, not only because Zika virus is a vertical transmission disease, but also because women—in Brazil and elsewhere—typically represent the primary carers of children. This is a qualitative analytic study using semi-structured interviews with 23 female family carers of children with CZS in Brazil. Through the concept of biographical disruption, we analysed some of the social impacts experienced by women involved in caring for affected children. We identified that the arrival of a child with disabilities resulted in biographical disruption similar to that experienced by people with chronic illnesses. Social support networks were configured through an alliance between women from different generations, revealing solidarity networks, but also highlighting the absence of the state in tackling these social vulnerabilities. Tracing the pathways of these biographical narratives enables us to understand how women have acted to defend the value of their disabled children in a society structured on the model of body normativity and inequality. These results may provide clues to a more inclusive society, which confronts systems of gender oppression and the sexual division of labour focused on women. Full article
16 pages, 955 KiB  
Article
Zika Virus Infection in a Cohort of Pregnant Women with Exanthematic Disease in Manaus, Brazilian Amazon
by Elijane de Fátima Redivo, Camila Bôtto Menezes, Márcia da Costa Castilho, Marianna Brock, Evela da Silva Magno, Maria das Graças Gomes Saraiva, Salete Sara Alvarez Fernandes, Anny Beatriz Costa Antony de Andrade, Maria das Graças Costa Alecrim and Flor Ernestina Martinez-Espinosa
Viruses 2020, 12(12), 1362; https://0-doi-org.brum.beds.ac.uk/10.3390/v12121362 - 28 Nov 2020
Cited by 10 | Viewed by 1965
Abstract
The epidemic transmission of Zika virus (ZIKV) in Brazil has been identified as a cause of microcephaly and other neurological malformations in the babies of ZIKV-infected women. The frequency of adverse outcomes of Zika virus infection (ZIKVi) in pregnancy differs depending on the [...] Read more.
The epidemic transmission of Zika virus (ZIKV) in Brazil has been identified as a cause of microcephaly and other neurological malformations in the babies of ZIKV-infected women. The frequency of adverse outcomes of Zika virus infection (ZIKVi) in pregnancy differs depending on the characteristics of exposure to infection, the time of recruitment of research participants, and the outcomes to be observed. This study provides a descriptive analysis—from the onset of symptoms to delivery—of a cohort registered as having maternal ZIKVi in pregnancy, from November 2015 to December 2016. Suspected cases were registered at a referral center for infectious and tropical diseases in Manaus, in the Amazonian region of Brazil. Of 834 women notified, 762 women with confirmed pregnancies were enrolled. Reverse-transcriptase polymerase chain reaction (RT-PCR) confirmed ZIKVi in 42.3% of the cohort. In 35.2% of the cohort, ZIKV was the sole infection identified. Severe adverse pregnancy outcomes (miscarriage, stillbirth, or microcephaly) were observed in both RT-PCR ZIKV-positive (5.0%) and ZIKV-negative (1.8%) cases (RR 3.1; 95% IC 1.4–7.3; p < 0.05), especially during the first trimester of pregnancy (RR 6.2, 95% IC 2.3–16.5; p < 0.001). Although other infectious rash diseases were observed in the pregnant women in the study, having confirmed maternal ZIKVi was the most important risk factor for serious adverse pregnancy events. Full article
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21 pages, 1548 KiB  
Article
Examining the Association of Socioeconomic Position with Microcephaly and Delayed Childhood Neurodevelopment among Children with Prenatal Zika Virus Exposure
by Grace M. Power, Suzanna C. Francis, Nuria Sanchez Clemente, Zilton Vasconcelos, Patricia Brasil, Karin Nielsen-Saines, Elizabeth B. Brickley and Maria E. Moreira
Viruses 2020, 12(11), 1342; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111342 - 23 Nov 2020
Cited by 10 | Viewed by 2613
Abstract
Increased rates of Zika virus have been identified in economically deprived areas in Brazil at the population level; yet, the implications of the interaction between socioeconomic position and prenatal Zika virus exposure on adverse neurodevelopmental outcomes remains insufficiently evaluated at the individual level. [...] Read more.
Increased rates of Zika virus have been identified in economically deprived areas in Brazil at the population level; yet, the implications of the interaction between socioeconomic position and prenatal Zika virus exposure on adverse neurodevelopmental outcomes remains insufficiently evaluated at the individual level. Using data collected between September 2015 and September 2019 from 163 children with qRT-PCR and/or IgM-confirmed prenatal exposure to Zika virus participating in a prospective cohort study in Rio de Janeiro, Brazil (NCT03255369), this study evaluated the relationships of socioeconomic indicators with microcephaly at birth and Bayley-III neurodevelopmental scores during the early life course. Adjusted logistic regression models indicated increased odds of microcephaly in children born to families with lower household income (OR, 95% CI: 3.85, 1.43 to 10.37) and higher household crowding (OR, 95% CI: 1.83, 1.16 to 2.91), while maternal secondary and higher education appeared to have a protective effect for microcephaly compared to primary education (OR, 95% CI: 0.33, 0.11 to 0.98 and 0.10, 0.03 to 0.36, respectively). Consistent with these findings, adjusted linear regression models indicated lower composite language (−10.78, 95% CI: −19.87 to −1.69), motor (−10.45, 95% CI: −19.22 to −1.69), and cognitive (−17.20, 95% CI: −26.13 to −8.28) scores in children whose families participated in the Bolsa Família social protection programme. As such, the results from this investigation further emphasise the detrimental effects of childhood disadvantage on human health and development by providing novel evidence on the link between individual level socioeconomic indicators and microcephaly and delayed early life neurodevelopment following prenatal Zika virus exposure. Full article
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14 pages, 646 KiB  
Article
Neurological Findings in Children without Congenital Microcephaly Exposed to Zika Virus in Utero: A Case Series Study
by Marília Rosa Abtibol-Bernardino, Lucíola de Fátima Albuquerque de Almeida Peixoto, Geruza Alfaia de Oliveira, Tatiane Freitas de Almeida, Gabriela Ribeiro Ivo Rodrigues, Rodrigo Haruo Otani, Beatriz Caroline Soares Chaves, Cristina de Souza Rodrigues, Anny Beatriz Costa Antony de Andrade, Elijane de Fatima Redivo, Salete Sara Fernandes, Marcia da Costa Castilho, Silvana Gomes Benzecry, Camila Bôtto-Menezes, Flor Ernestina Martinez-Espinosa and Maria das Graças Costa Alecrim
Viruses 2020, 12(11), 1335; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111335 - 20 Nov 2020
Cited by 17 | Viewed by 2814
Abstract
The Zika virus can induce a disruptive sequence in the fetal brain and is manifested mainly by microcephaly. Knowledge gaps still exist as to whether the virus can cause minor disorders that are perceived later on during the first years of life in [...] Read more.
The Zika virus can induce a disruptive sequence in the fetal brain and is manifested mainly by microcephaly. Knowledge gaps still exist as to whether the virus can cause minor disorders that are perceived later on during the first years of life in children who are exposed but are asymptomatic at birth. In this case series, we describe the outcomes related to neurodevelopment through the neurological assessment of 26 non-microcephalic children who had intrauterine exposure to Zika virus. Children were submitted for neurological examinations and Bayley Scales-III (cognition, language, and motor performance). The majority (65.4%) obtained satisfactory performance in neurodevelopment. The most impaired domain was language, with 30.7% impairment. Severe neurological disorders occurred in five children (19.2%) and these were spastic hemiparesis, epilepsy associated with congenital macrocephaly (Zika and human immunodeficiency virus), two cases of autism (one exposed to Zika and Toxoplasma gondii) and progressive sensorineural hearing loss (GJB2 mutation). We concluded that non-microcephalic children with intrauterine exposure to Zika virus, in their majority, had achieved satisfactory performance in all neurodevelopmental domains. One third of the cases had some impairment, but the predominant group had mild alterations, with low occurrence of moderate to severe disorders, similar to other studies in Brazil. Full article
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11 pages, 558 KiB  
Article
Can Zika Virus Infection in High Risk Pregnant Women Be Differentiated on the Basis of Symptoms?
by Nuria Sanchez Clemente, Elizabeth B. Brickley, Marcia Furquim de Almeida, Steven S. Witkin, Saulo Duarte Passos and the Jundiai Zika Cohort Group
Viruses 2020, 12(11), 1263; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111263 - 05 Nov 2020
Cited by 4 | Viewed by 1648
Abstract
Zika virus (ZIKV) infection in pregnancy is associated with congenital neurological abnormalities. Our understanding of the full clinical spectrum of ZIKV infection is incomplete. Using data from this prospective cohort study consisting of 650 women attending a high-risk pregnancy clinic during the Zika [...] Read more.
Zika virus (ZIKV) infection in pregnancy is associated with congenital neurological abnormalities. Our understanding of the full clinical spectrum of ZIKV infection is incomplete. Using data from this prospective cohort study consisting of 650 women attending a high-risk pregnancy clinic during the Zika virus outbreak in Brazil, we investigated the extent to which specific symptoms can be utilized to differentiate ZIKV-infected pregnant women from those with other pregnancy-related problems. All were tested for ZIKV in urine by RT–qPCR. Demographic and clinical data including physical symptoms during follow-up were recorded and analyzed with respect to Zika virus exposure status. Forty-eight (7.4%) women were positive for ZIKV by RT–qPCR. The majority (70.8%) were asymptomatic, and only four ZIKV-positive women (8.3%) reported symptoms during pregnancy that met the WHO case definition. Zika-positive and -negative women reported similar frequencies of ZIKV-like symptoms (as per the WHO definition): fever (16.7% vs. 13.6%), arthralgia/arthritis (10.4% vs. 11.3%), rash (4.2% vs. 5.3%), and conjunctivitis (2.1% vs. 3.2%). Most pregnant women positive for ZIKV in urine are asymptomatic and do not deliver a baby with microcephaly. Physical symptoms alone did not differentiate between high-risk pregnant women positive or negative for ZIKV. Full article
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13 pages, 285 KiB  
Article
Plaque Reduction Neutralization Test (PRNT) in the Congenital Zika Syndrome: Positivity and Associations with Laboratory, Clinical, and Imaging Characteristics
by Marizélia R. C. Ribeiro, Ricardo Khouri, Patrícia S. Sousa, Maria R. F. C. Branco, Rosângela F. L. Batista, Elaine P. F. Costa, Maria T. S. S. B. Alves, Gláucio A. Amaral, Marcella C. R. Borges, Eliana H. M. Takahasi, Líllian N. Gomes, Ana K. T. Mendes, Tamires B. Cavalcante, Luciana C. Costa, Alvina C. Félix, Nathalia C. S. Souza and Antônio A. M. Silva
Viruses 2020, 12(11), 1244; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111244 - 31 Oct 2020
Cited by 14 | Viewed by 2538
Abstract
The short duration of viremia, low blood viral load, inaccessibility to timely specific diagnostic tests, and cross-reactions with other flaviviruses have hindered laboratory confirmation of Congenital Zika Syndrome (CZS). This study analyzes the positivity of the plaque reduction neutralization test (PRNT) in children [...] Read more.
The short duration of viremia, low blood viral load, inaccessibility to timely specific diagnostic tests, and cross-reactions with other flaviviruses have hindered laboratory confirmation of Congenital Zika Syndrome (CZS). This study analyzes the positivity of the plaque reduction neutralization test (PRNT) in children with clinical or imaging characteristics of CZS and its association with laboratory, clinical, and imaging characteristics. The 94 clinical cases of CZS submitted to the ZIKV PRNT90 test were followed from 2016 to 2018. The mean age of children at PRNT90 collection was 22 ± 6 months Standard Deviation. The ZIKV PRNT90 was positive (titer ≥ 10) in 40 (42.5%) children. ZIKV PRNT90 positivity was associated with severe microcephaly in newborns (p = 0.016), lower head circumference z-score at birth (p = 0.043) and 24 months of age (p = 0.031), and severe reduction of the cerebral parenchyma volume (p = 0.021), expressing greater disease severity. Negative PRNT90 in children with characteristic signs of CZS may be due to false-negative results, indicating that the diagnosis of CZS should be primarily syndromic. Full article
12 pages, 921 KiB  
Article
Case Fatality Rate Related to Microcephaly Congenital Zika Syndrome and Associated Factors: A Nationwide Retrospective Study in Brazil †
by Maria Conceição N. Costa, Luciana Lobato Cardim, Maria Gloria Teixeira, Mauricio L. Barreto, Rita de Cassia Oliveira de Carvalho-Sauer, Florisneide R. Barreto, Martha Suely Itaparica Carvalho, Wanderson K. Oliveira, Giovanny V. A. França, Eduardo Hage Carmo, Roberto F. S Andrade, Moreno S. Rodrigues, Rafael V. Veiga, Juliane F. Oliveira, Qeren H. R. F. Fernandes, Larissa C. Costa, Giovanini E. Coelho and Enny S. Paixao
Viruses 2020, 12(11), 1228; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111228 - 29 Oct 2020
Cited by 14 | Viewed by 2423
Abstract
Background: The clinical manifestations of microcephaly/congenital Zika syndrome (microcephaly/CZS) have harmful consequences on the child’s health, increasing vulnerability to childhood morbidity and mortality. This study analyzes the case fatality rate and child–maternal characteristics of cases and deaths related to microcephaly/CZS in Brazil, 2015–2017. [...] Read more.
Background: The clinical manifestations of microcephaly/congenital Zika syndrome (microcephaly/CZS) have harmful consequences on the child’s health, increasing vulnerability to childhood morbidity and mortality. This study analyzes the case fatality rate and child–maternal characteristics of cases and deaths related to microcephaly/CZS in Brazil, 2015–2017. Methods: Population-based study developed by linkage of three information systems. We estimate frequencies of cases, deaths, case fatality rate related to microcephaly/CZS according to child and maternal characteristics and causes of death. Multivariate logistic regression models were applied. Results: The microcephaly/CZS case fatality rate was 10% (95% CI 9.2–10.7). Death related to microcephaly/CZS was associated to moderate (OR = 2.15; 95% CI 1.63–2.83), and very low birth weight (OR = 3.77; 95% CI 2.20–6.46); late preterm births (OR = 1.65; 95% CI 1.21–2.23), Apgar < 7 at 1st (OR = 5.98; 95% CI 4.46–8.02) and 5th minutes (OR = 4.13; 95% CI 2.78–6.13), among others. Conclusions: A high microcephaly/CZS case fatality rate and important factors associated with deaths related to this syndrome were observed. These results can alert health teams to these problems and increase awareness about the factors that may be associated with worse outcomes. Full article
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13 pages, 321 KiB  
Article
Neurological Development, Epilepsy, and the Pharmacotherapy Approach in Children with Congenital Zika Syndrome: Results from a Two-Year Follow-up Study
by Maria Eulina Quilião, Fabio Antonio Venancio, Lisany Krug Mareto, Sahra de Almeida Metzker, Ana Isabel do Nascimento, Daniele Cristina Vitorelli-Venancio, Cláudia Du Bocage Santos-Pinto and Everton Falcão de Oliveira
Viruses 2020, 12(10), 1083; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101083 - 25 Sep 2020
Cited by 11 | Viewed by 2490
Abstract
Clinical outcomes related to congenital Zika syndrome (CZS) include microcephaly accompanied by specific brain injuries. Among several CZS outcomes that have been described, epilepsy and motor impairments are present in most cases. Pharmacological treatment for seizures resulting from epilepsy is performed with anticonvulsant [...] Read more.
Clinical outcomes related to congenital Zika syndrome (CZS) include microcephaly accompanied by specific brain injuries. Among several CZS outcomes that have been described, epilepsy and motor impairments are present in most cases. Pharmacological treatment for seizures resulting from epilepsy is performed with anticonvulsant drugs, which in the long term are related to impairments in the child’s neuropsychomotor development. Here, we describe the results from a two-year follow-up of a cohort of children diagnosed with CZS related to the growth of the head circumference and some neurological and motor outcomes, including the pharmacological approach, and its results in the treatment of epileptic seizures. This paper is part of a prospective cohort study carried out in the state of Mato Grosso Sul, Brazil, based on a Zika virus (ZIKV)-exposed child population. Our data were focused on the assessment of head circumference growth and some neurological and motor findings, including the description of seizure conditions and pharmacological management in two periods. Among the 11 children evaluated, 8 had severe microcephaly associated with motor impairment and/or epilepsy. Seven children were diagnosed with epilepsy. Of these, 3 had West syndrome. In four children with other forms of epilepsy, there was no pharmacological control. Full article

Review

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17 pages, 738 KiB  
Review
A Glimmer of Hope: Recent Updates and Future Challenges in Zika Vaccine Development
by Priscila M. S. Castanha and Ernesto T. A. Marques
Viruses 2020, 12(12), 1371; https://0-doi-org.brum.beds.ac.uk/10.3390/v12121371 - 30 Nov 2020
Cited by 17 | Viewed by 3458
Abstract
The emergence and rapid spread of Zika virus (ZIKV) on a global scale as well as the establishment of a causal link between Zika infection and congenital syndrome and neurological disorders triggered unprecedented efforts towards the development of a safe and effective Zika [...] Read more.
The emergence and rapid spread of Zika virus (ZIKV) on a global scale as well as the establishment of a causal link between Zika infection and congenital syndrome and neurological disorders triggered unprecedented efforts towards the development of a safe and effective Zika vaccine. Multiple vaccine platforms, including purified inactivated virus, nucleic acid vaccines, live-attenuated vaccines, and viral-vectored vaccines, have advanced to human clinical trials. In this review, we discuss the recent advances in the field of Zika vaccine development and the challenges for future clinical efficacy trials. We provide a brief overview on Zika vaccine platforms in the pipeline before summarizing the vaccine candidates in clinical trials, with a focus on recent, promising results from vaccine candidates that completed phase I trials. Despite low levels of transmission during recent years, ZIKV has become endemic in the Americas and the potential of large Zika outbreaks remains real. It is important for vaccine developers to continue developing their Zika vaccines, so that a potential vaccine is ready for deployment and clinical efficacy trials when the next ZIKV outbreak occurs. Full article
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Other

Jump to: Research, Review

13 pages, 494 KiB  
Study Protocol
Zika Brazilian Cohorts (ZBC) Consortium: Protocol for an Individual Participant Data Meta-Analysis of Congenital Zika Syndrome after Maternal Exposure during Pregnancy
by Maria das Graças Costa Alecrim, Melania Maria Ramos de Amorim, Thalia Velho Barreto de Araújo, Patrícia Brasil, Elizabeth B. Brickley, Marcia da Costa Castilho, Bernadete Perez Coelho, Antônio José Ledo Alves da Cunha, Geraldo Duarte, Cássia Fernanda Estofolete, Ricardo Queiroz Gurgel, Juliana Herrero-Silva, Cristina Barroso Hofer, Aline Siqueira Alves Lopes, Celina Maria Turchi Martelli, Adriana Suely de Oliveira Melo, Demócrito de Barros Miranda-Filho, Ulisses Ramos Montarroyos, Maria Elisabeth Moreira, Marisa Marcia Mussi-Pinhata, Consuelo Silva de Oliveira, Saulo Duarte Passos, Arnaldo Prata-Barbosa, Darci Neves dos Santos, Lavínia Schuler-Faccini, Antônio Augusto Moura da Silva, Isadora Cristina de Siqueira, Patrícia da Silva Sousa, Marília Dalva Turchi, Ricardo Arraes de Alencar Ximenes, Ana Laura de Sene Amâncio Zara and Zika Brazilian Cohorts Consortium (ZBC-Consortium)add Show full author list remove Hide full author list
Viruses 2021, 13(4), 687; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040687 - 16 Apr 2021
Cited by 8 | Viewed by 3123
Abstract
Despite great advances in our knowledge of the consequences of Zika virus to human health, many questions remain unanswered, and results are often inconsistent. The small sample size of individual studies has limited inference about the spectrum of congenital Zika manifestations and the [...] Read more.
Despite great advances in our knowledge of the consequences of Zika virus to human health, many questions remain unanswered, and results are often inconsistent. The small sample size of individual studies has limited inference about the spectrum of congenital Zika manifestations and the prognosis of affected children. The Brazilian Zika Cohorts Consortium addresses these limitations by bringing together and harmonizing epidemiological data from a series of prospective cohort studies of pregnant women with rash and of children with microcephaly and/or other manifestations of congenital Zika. The objective is to estimate the absolute risk of congenital Zika manifestations and to characterize the full spectrum and natural history of the manifestations of congenital Zika in children with and without microcephaly. This protocol describes the assembly of the Consortium and protocol for the Individual Participant Data Meta-analyses (IPD Meta-analyses). The findings will address knowledge gaps and inform public policies related to Zika virus. The large harmonized dataset and joint analyses will facilitate more precise estimates of the absolute risk of congenital Zika manifestations among Zika virus-infected pregnancies and more complete descriptions of its full spectrum, including rare manifestations. It will enable sensitivity analyses using different definitions of exposure and outcomes, and the investigation of the sources of heterogeneity between studies and regions. Full article
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