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14 pages, 266 KiB

Open AccessArticle

Neonatal Microcephaly and Central Nervous System Abnormalities During the Zika Outbreak in Rio de Janeiro

by Marlos Melo Martins, Roberto de Andrade Medronho, Carlos Eduardo Raymundo, Arnaldo Prata-Barbosa and Antonio José Ledo Alves da Cunha

Viruses 2025, 17(2), 208; https://doi.org/10.3390/v17020208 - 31 Jan 2025

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Abstract

This retrospective cohort study analyzed 7870 pregnant women, including 2269 with confirmed Zika virus (ZIKV) infection and 5601 without Zika infection, along with their fetuses and newborns. Data were sourced from multiple databases in the state of Rio de Janeiro, Brazil. A propensity [...] Read more.

This retrospective cohort study analyzed 7870 pregnant women, including 2269 with confirmed Zika virus (ZIKV) infection and 5601 without Zika infection, along with their fetuses and newborns. Data were sourced from multiple databases in the state of Rio de Janeiro, Brazil. A propensity score model was employed to control confounding factors and stratify outcomes by pregnancy trimester. Among ZIKV+ pregnant women, 49 cases of congenital microcephaly or congenital nervous system (CNS) abnormalities were identified (2.16%, or 193.9 cases in 10,000 live births), whereas 44 cases were identified among ZIKV− women (0.78%, or 71.4 cases in 10,000 live births). Multivariable analysis yielded an odds ratio of 2.46 (95% CI 1.30–4.64) overall, with 4.29 (95% CI 1.93–9.53) in the first trimester, 5.29 (95% CI 1.08–25.95) in the second trimester, and 0.68 (95% CI 0.21–2.14) in the third trimester. The most frequent findings among ZIKV+ cases included intracranial calcifications, ventriculomegaly, posterior fossa malformations, reduced brain volume, corpus callosum malformations, cortex dysplasia, lissencephaly, and pachygyria. Ophthalmologic abnormalities were detected in 55.5% of cases, and brainstem auditory evoked potential anomalies were reported in 33.3%. ZIKV infection can result in structural or functional anomalies. Given the absence of specific treatment for congenital Zika syndrome (CZS), clinical care should prioritize monitoring and managing neurological, motor, auditory, visual, and orthopedic disorders in all children with in utero ZIKV exposure, especially during the first and second trimesters of pregnancy. Full article

(This article belongs to the Special Issue Zika Virus and Congenital Zika Syndrome)

7 pages, 819 KiB

Open AccessArticle

3D Head Shape Feature Analysis of Zika-Infected Children

by Xiangyang Ju, Peter Mossey and Ashraf Ayoub

Viruses 2024, 16(9), 1406; https://doi.org/10.3390/v16091406 - 3 Sep 2024

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Abstract

Congenital Zika syndrome (CZS) has been identified a constellation of congenital anomalies caused by Zika Virus (ZKV) infection during pregnancy. The infection with ZKV could lead to microcephaly of the fetus due to a severe decrease in brain volume and reduced brain growth. [...] Read more.

Congenital Zika syndrome (CZS) has been identified a constellation of congenital anomalies caused by Zika Virus (ZKV) infection during pregnancy. The infection with ZKV could lead to microcephaly of the fetus due to a severe decrease in brain volume and reduced brain growth. The preliminary screening of CZS is based on measuring head circumference; the diagnosis is made if this measurement is below two standard deviations below the mean. The analyses of the 3D head features of infected infants are limited. This study analyzed 3D head images of 35 ZKV-positive cases with an average age of 16.8 ± 2 months and 35 controls with an average age of 14.4 ± 5 months. This study focused on identifying potential diagnostic characteristics of CZS. The 3D head images were captured using a 3D imaging system. The averaged images of the two groups were aligned to illustrate the size and shape differences. There were significant differences in centroid size, head circumference (HC), head height (HH), and chin height (CH) between the two groups. We also identified significant differences in the indices of chin height/total facial height (CH/TFH) and head height/head circumference ratio (HH/HC) between the CZS and control cases. An HH/HC of 0.49 showed a sensitivity of 0.86 and a specificity of 0.74 in diagnosing CZS, which is more sensitive than the routinely used HC measurement. The index of HH/HC has potential to be used as the gold standard for the early screening for the detection of CZS cases. Full article

(This article belongs to the Special Issue Zika Virus and Congenital Zika Syndrome)

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13 pages, 495 KiB

Open AccessArticle

Comparative Evaluation of Select Serological Assays for Zika Virus Using Blinded Reference Panels

by Devy M. Emperador, Mars Stone, Eduard Grebe, Camille Escadafal, Honey Dave, Eve Lackritz, Cassandra Kelly-Cirino, Ingrid Rabe, Diana P. Rojas, Michael P. Busch and Graham Simmons

Viruses 2024, 16(7), 1075; https://doi.org/10.3390/v16071075 - 3 Jul 2024

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Abstract

In response to the 2015 Zika virus (ZIKV) epidemic that occurred in Brazil, numerous commercial serological assays have been developed for clinical and research applications. Diagnosis of recent infection in pregnant women remains challenging. Having standardized, comparative studies of ZIKV tests is important [...] Read more.

In response to the 2015 Zika virus (ZIKV) epidemic that occurred in Brazil, numerous commercial serological assays have been developed for clinical and research applications. Diagnosis of recent infection in pregnant women remains challenging. Having standardized, comparative studies of ZIKV tests is important for implementing optimal diagnostic testing and disease surveillance. This is especially important for serology tests used to detect ZIKV infection given that antibodies against ZIKV can cross-react with other arboviruses in the same virus family, such as dengue virus (DENV), yellow fever virus (YFV) and West Nile virus (WNV). We looked at the sensitivity and specificity of tests detecting ZIKV antibodies (IgM, IgG) from multiple manufacturers using panels of samples previously collected with known exposure to ZIKV and other arboviruses. We found that performance of the IgM tests was highly variable, with only one test (Inbios 2.0 IgM capture ELISA) having both high sensitivity and specificity. All IgG tests showed good sensitivity; however, specificity was highly variable, with some assays giving false-positive results on samples infected by another flavivirus. Overall, the results confirmed that accurate ZIKV antibody testing is challenging, especially in specimens from regions endemic for multiple other flaviviruses, and highlight the importance of available and suitable reference samples to evaluate ZIKV diagnostics. Full article

(This article belongs to the Special Issue Zika Virus and Congenital Zika Syndrome)

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9 pages, 2078 KiB

Open AccessArticle

Serological Evidence of Zika Virus Infections in Sudan

by Awadalkareem Adam, Robert Wenzel, Elisabeth Unger, Sven Reiche and Christian Jassoy

Viruses 2024, 16(7), 1045; https://doi.org/10.3390/v16071045 - 28 Jun 2024

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Abstract

Little is known about the frequency of Zika virus (ZIKV) infections in Sudan. The aim of this study was to obtain data on the prevalence of ZIKV infections and the immunity of the population in the country. To this end, 198 sera obtained [...] Read more.

Little is known about the frequency of Zika virus (ZIKV) infections in Sudan. The aim of this study was to obtain data on the prevalence of ZIKV infections and the immunity of the population in the country. To this end, 198 sera obtained between December 2012 and January 2013 in different regions in Sudan were examined for neutralizing antibodies against ZIKV, dengue virus (DENV), and yellow fever virus (YFV). The sera were non-randomly selected. The neutralization titers were compared with each other and with the WHO 1st International Standard for anti-Asian lineage Zika virus antibody. Twenty-six sera neutralized ZIKV. One-third of these sera had higher neutralization titers against ZIKV than against DENV-2 and -3. Two sera showed higher neutralization titers than the WHO standard for ZIKV antibodies. These data suggest occasional ZIKV infections in Sudan. The low percentage of sera in this cohort that neutralized ZIKV indicates that, in the study period, the population was susceptible to ZIKV infection. Full article

(This article belongs to the Special Issue Zika Virus and Congenital Zika Syndrome)

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12 pages, 2762 KiB

Open AccessArticle

Association between Sleep and Language Development in Children with Congenital Zika Syndrome

by Nathani C. da Silva, Celia M. Giacheti, Maria C. H. do Couto, Stefany S. de Jesus, Erlane M. Ribeiro, Islane M. C. Verçosa and Luciana Pinato

Viruses 2024, 16(7), 1003; https://doi.org/10.3390/v16071003 - 22 Jun 2024

Cited by 1 | Viewed by 866

Abstract

AIM: Congenital Zika Virus Syndrome (CZS) presents notable hurdles to neurodevelopment, with language development emerging as a crucial aspect. This study investigates sleep patterns and language skills in children with CZS, aiming to explore the potential synchronization of sleep development with their neurodevelopment. [...] Read more.

AIM: Congenital Zika Virus Syndrome (CZS) presents notable hurdles to neurodevelopment, with language development emerging as a crucial aspect. This study investigates sleep patterns and language skills in children with CZS, aiming to explore the potential synchronization of sleep development with their neurodevelopment. METHOD: We studied cross-sectionally 135 children with CZS aged 0 to 48 months, investigating sleep using the BISQ Questionnaire. Language development was assessed using the Early Language Milestone Scale, while motor development and cognitive and social ability were assessed using the Bayley Scales of Infant and Young Child Development 3rd edition. We also studied longitudinally a cohort of 16 children (initially aged 0 to 12 months) whom we followed for four years, assessing at one-year intervals. RESULTS: Sleep disturbances and language deficits were highly frequent in this population. In the 0–12 months group, a late bedtime and frequent nighttime awakenings were associated with poorer auditory expressive skills. At 13–24 months, nighttime awakenings were associated with poorer auditory expressive skills, while among 25–36-month-olds decreased auditory receptive skills were associated with longer sleep onset latency and reduced nighttime sleep duration. CONCLUSION: The brain alterations caused by Zika virus infection affect both sleep disturbances and delays in language development. It is possible that sleep disturbance may be a mediating factor in the pathway between CZS and delayed language development, as the three analyzed language skills showed a correlation with sleep parameters. Full article

(This article belongs to the Special Issue Zika Virus and Congenital Zika Syndrome)

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13 pages, 318 KiB

Open AccessArticle

Clinical and Acoustic Alterations of Swallowing in Children Exposed to Zika Virus during Pregnancy in a Cohort in Amazonas, Brazil: A Case Series Study

by Cristina de Souza Rodrigues, Raillon Keven Santos Souza, Cosmo Vieira Rocha Neto, Rodrigo Haruo Otani, Daniel de Medeiros Batista, Ana Karla Nelson de Oliveira Maia, Kleber Pinheiro de Oliveira Filho, Thais Dourado de Andrade, Emmilyn de Andrade Almeida, Luiz Henrique Gonçalves Maciel, Lucíola de Fátima Albuquerque Almeida Peixoto Castro, Marília Rosa Abtibol-Bernardino, Djane Clarys Baia-da-Silva, Silvana Gomes Benzecry, Marcia da Costa Castilho, Flor Ernestina Martínez-Espinosa, Maria das Graças Costa Alecrim, Rosane Sampaio Santos and Camila Botto-Menezes

Viruses 2023, 15(12), 2363; https://doi.org/10.3390/v15122363 - 30 Nov 2023

Cited by 1 | Viewed by 1768

Abstract

Oropharyngeal dysphagia (OD) is a swallowing disorder that involves difficulty in safely passing the food bolus from the oral cavity to the stomach. OD is a common problem in children with congenital Zika virus syndrome (CZS). In this case series, we describe the [...] Read more.

Oropharyngeal dysphagia (OD) is a swallowing disorder that involves difficulty in safely passing the food bolus from the oral cavity to the stomach. OD is a common problem in children with congenital Zika virus syndrome (CZS). In this case series, we describe the clinical and acoustic alterations of swallowing in children exposed to the Zika virus during pregnancy in a cohort from Amazonas, Brazil. From July 2019 to January 2020, 22 children were evaluated, 6 with microcephaly and 16 without microcephaly. The mean age among the participants was 35 months (±4.6 months). All children with microcephaly had alterations in oral motricity, mainly in the lips and cheeks. Other alterations were in vocal quality, hard palate, and soft palate. Half of the children with microcephaly showed changes in cervical auscultation during breast milk swallowing. In children without microcephaly, the most frequently observed alteration was in lip motricity, but alterations in auscultation during the swallowing of breast milk were not observed. Regarding swallowing food of a liquid and pasty consistency, the most frequent alterations were incomplete verbal closure, increased oral transit time, inadequacy in capturing the spoon, anterior labial leakage, and increased oral transit time. Although these events are more frequent in microcephalic children, they can also be seen in non-microcephalic children, which points to the need for an indistinct evaluation of children exposed in utero to ZIKV. Full article

(This article belongs to the Special Issue Zika Virus and Congenital Zika Syndrome)

14 pages, 2212 KiB

Open AccessArticle

Low CCL2 and CXCL8 Production and High Prevalence of Allergies in Children with Microcephaly Due to Congenital Zika Syndrome

by Wallace Pitanga Bezerra, Amanda Costa Ayres Salmeron, Anna Cláudia Calvielli Castelo Branco, Ingryd Camara Morais, Valéria Soraya de Farias Sales, Paula Renata Lima Machado, Janeusa Trindade Souto, Josélio Maria Galvão de Araújo, Paulo Marcos da Matta Guedes, Maria Notomi Sato and Manuela Sales Lima Nascimento

Viruses 2023, 15(9), 1832; https://doi.org/10.3390/v15091832 - 29 Aug 2023

Cited by 1 | Viewed by 1496

Abstract

Congenital Zika Syndrome (CZS) is associated with an increased risk of microcephaly in affected children. This study investigated the peripheral dysregulation of immune mediators in children with microcephaly due to CZS. Gene expression quantified by qPCR in whole blood samples showed an increase [...] Read more.

Congenital Zika Syndrome (CZS) is associated with an increased risk of microcephaly in affected children. This study investigated the peripheral dysregulation of immune mediators in children with microcephaly due to CZS. Gene expression quantified by qPCR in whole blood samples showed an increase in IFNγ and IL-13 transcripts in children affected with microcephaly compared to the control group. The microcephaly group exhibited significantly decreased CCL2 and CXCL8 levels in serum, quantified by CBA assay. An allergic profile questionnaire revealed a high prevalence of allergies in the microcephaly group. In accordance, elevated serum IgE level measured by the Proquantum Immunoassay was observed in children affected with microcephaly compared to the control group. Altogether, these findings show a persistent systemic inflammation in children with microcephaly due to CZS and suggest a possible impairment in leukocyte migration caused by low production of CCL2 and CXCL8, in addition to high levels of IgE associated with high prevalence of allergies. The dysregulation of inflammatory genes and chemokines underscores the importance of understanding the immunological characteristics of CZS. Further investigation into the long-term consequences of systemic inflammation in these children is crucial for developing appropriate therapeutic strategies and tailored vaccination protocols. Full article

(This article belongs to the Special Issue Zika Virus and Congenital Zika Syndrome)

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7 pages, 282 KiB

Open AccessBrief Report

Does the Presence or a High Titer of Yellow Fever Virus Antibodies Interfere with Pregnancy Outcomes in Women with Zika Virus Infection?

by Isa Cristina Ribeiro Piauilino, Raillon Keven dos Santos Souza, Maurício Teixeira Lima, Yanka Karolinna Batista Rodrigues, Luís Felipe Alho da Silva, Ayrton Sena Gouveia, Alexandre Vilhena da Silva Neto, Bárbara Aparecida Chaves, Maria das Graças Costa Alecrim, Camila Helena Aguiar Bôtto de Menezes, Márcia da Costa Castilho, Djane Clarys Baia-da-Silva and Flor Ernestina Martinez Espinosa

Viruses 2023, 15(11), 2244; https://doi.org/10.3390/v15112244 - 11 Nov 2023

Cited by 1 | Viewed by 1438

Abstract

Zika virus (ZIKV) and yellow fever virus (YFV) originated in Africa and expanded to the Americas, where both are co-circulated. It is hypothesized that in areas of high circulation and vaccination coverage against YFV, children of pregnant women have a lower risk of [...] Read more.

Zika virus (ZIKV) and yellow fever virus (YFV) originated in Africa and expanded to the Americas, where both are co-circulated. It is hypothesized that in areas of high circulation and vaccination coverage against YFV, children of pregnant women have a lower risk of microcephaly. We evaluated the presence and titers of antibodies and outcomes in women who had ZIKV infection during pregnancy. Pregnancy outcomes were classified as severe, moderate, and without any important outcome. An outcome was defined as severe if miscarriage, stillbirth, or microcephaly occurred, and moderate if low birth weight and/or preterm delivery occurred. If none of these events were identified, the pregnancy was defined as having no adverse effects. A sample of 172 pregnant women with an acute ZIKV infection confirmed during pregnancy were collected throughout 2016. About 89% (150 of 169) of them presented immunity against YFV, including 100% (09 of 09) of those who had severe outcomes, 84% (16 of 19) of those who had moderate outcomes, and 89% (125 of 141) of those who had non-outcomes. There was no difference between groups regarding the presence of anti-YFV antibodies (p = 0.65) and YFV titers (p = 0.6). We were unable to demonstrate a protective association between the presence or titers of YFV antibodies and protection against serious adverse outcomes from exposure to ZIKV in utero. Full article

(This article belongs to the Special Issue Zika Virus and Congenital Zika Syndrome)

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