Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 2.852
Filter
1.
Eur J Pediatr ; 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34596742

ABSTRACT

Congenital Zika Syndrome (CZS) is characterized by many impairments especially in the central nervous system, potentially compromising neurodevelopment and causing significant morbidity in affected children. The aim was to assess gross motor function in children with CZS. This was a cross-sectional investigation nested within a prospective cohort study of children with CZS based in a Brazilian referral hospital in Rio de Janeiro. Between March/2017 and February/2018, we performed gross motor function assessments using the Gross Motor Function Classification (GMFCS) and the Gross Motor Function Measure (GMFM), estimating the mean and standard deviation of GMFM scores among GMFCS groups. The study sample included 72 children, with a median age of 13 months (7-25). Of these, 63 (87.5%) had severe motor impairment, 3 (4%) had moderate impairment, and 6 (8%) had mild impairment. The mean GMFM score for each group was respectively 11.6, 26.1, and 81.6, with statistically significant differences (p-value < 0.001). Severely affected children only achieved head control in the sitting posture when supported. Children with milder forms were able to develop walking skills.Conclusion: Most children with CZS have major motor disabilities and a poor prognosis. Better understanding of limitations and functionality in children with CZS can serve as a prognostic guide in their management. What is Known: • Severe motor impairment was present in 63 (87.5%) children with CZS. • The degree of neurological impairment was inversely associated with motor performance. What is New: • Microcephaly was more frequent among children with severe gross motor function impairment. • Children with CZS have major motor disabilities and a poor prognosis.

2.
Am J Trop Med Hyg ; 2021 Oct 04.
Article in English | MEDLINE | ID: mdl-34610572

ABSTRACT

Zika virus (ZIKV) is transmitted primarily through infected Aedes aegypti or Aedes albopictus mosquitoes. ZIKV infection during pregnancy was linked to adverse fetal/infant outcomes, including microcephaly, brain anomalies, ocular disorders, intrauterine growth restriction, and other congenital malformations. Human anti-Zika virus immunoglobulin (ZIKV-Ig) is being developed for prophylaxis of ZIKV in at-risk populations, including women of childbearing potential and pregnant women. A phase 1 single-center, double-blind, randomized, placebo-controlled study was conducted to assess the safety and pharmacokinetics (PK) of a single 50.0-mL ZIKV-Ig intravenous dose in healthy adult male or non-pregnant female subjects 18 to 55 years of age. Subjects received either ZIKV-Ig (n = 19) or saline placebo (n = 11). Safety was evaluated based on adverse events (AEs), laboratory test results, physical examinations, and vital signs. Overall, there were 11 subjects (36.7%) with treatment-related AEs including eight subjects (42.1%) in the ZIKV-Ig group and three subjects (27.3%) in the placebo group. Of the AEs considered treatment related, three subjects (15.8%) experienced headache (mild). There were no serious AEs, no deaths, and no discontinuations resulting from AEs. Overall, the safety profile of ZIKV-Ig in this study population of healthy adult subjects appeared to be safe and well tolerated. The results of the pharmacokinetic analysis determined that ZIKV-Ig had a maximum observed concentration of 182.3 U/mL (coefficient of variation, 21.3%), the time at which Cmax occurred of 2.3 hours ± 1.0 (SD), an area under the concentration-time curve0-∞ of 77,224 h × U/mL (coefficient of variation, 17.9%), and a half-life of 28.1 days, which is similar to other human-derived commercial Ig intravenous products.

3.
Molecules ; 26(19)2021 Sep 28.
Article in English | MEDLINE | ID: mdl-34641413

ABSTRACT

Zika virus (ZIKV) is a mosquito-borne virus belonging to the Flaviviridae family and is responsible for an exanthematous disease and severe neurological manifestations, such as microcephaly and Guillain-Barré syndrome. ZIKV has a single strand positive-sense RNA genome that is translated into structural and non-structural (NS) proteins. Although it has become endemic in most parts of the tropical world, Zika still does not have a specific treatment. Thus, in this work we evaluate the cytotoxicity and antiviral activities of 14 hybrid compounds formed by 1H-1,2,3-triazole, naphthoquinone and phthalimide groups. Most compounds showed low cytotoxicity to epithelial cells, specially the 3b compound. After screening with all compounds, 4b was the most active against ZIKV in the post-infection test, obtaining a 50% inhibition concentration (IC50) of 146.0 µM and SI of 2.3. There were no significant results for the pre-treatment test. According to the molecular docking compound, 4b was suggested with significant binding affinity for the NS5 RdRp protein target, which was further corroborated by molecular dynamic simulation studies.

4.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166285, 2021 Oct 06.
Article in English | MEDLINE | ID: mdl-34624499

ABSTRACT

During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants (<12 months of age). However, they might be at higher risk for progression to severe COVID-19 disease compared with older children. The data on clinical presentation and disease severity among neonates are limited and based on case reports and small case series. It is well documented the importance of the Zika virus infection as the main cause of several congenital anomalies and birth defects such as microcephaly, and also adverse pregnancy outcomes. Mycoplasma infections also increase adverse pregnancy outcomes. This review will focus on the molecular, pathophysiological and biophysical characteristics of the mother/placental-fetal/neonatal interactions and the possible mechanisms of these pathogens (SARS-CoV-2, ZIKV, and Mycoplasmas) for promoting disease at this level.

5.
Colloids Surf B Biointerfaces ; 208: 112120, 2021 Sep 16.
Article in English | MEDLINE | ID: mdl-34597940

ABSTRACT

In 2016, the Zika virus (ZIKV) infection became a major public health problem, after the discovery that an alarming increase in the number of Brazilian newborns with microcephaly could be associated with the occurrence of this viral disease during the pregnancy of their mothers. The urgent need for simple diagnostic methods that allow rapid screening of suspected cases has stimulated the search for low-cost devices capable of detecting specific sequences of nucleic acids. The present work describes the development of nanostructured films formed by bilayers of conjugated polymers for rapid detection of the presence of Zika virus DNA, via fluorescence methods. For this, we initially deposited alternating layers of polyaniline (PANI) and polypyrrole (PPY) on the surface of polyethylene terephthalate (PET) sheets. The films obtained were then characterized by SEM, UV-Vis, ATR-FTIR, and contact angle measurements. For their use as quenchers for the diagnosis of Zika, a single DNA strand-specific for ZIKV was labeled with a fluorophore (FAM-ssDNA). We determined the time required for the saturation of the interaction between probe FAM-ssDNA and the film (180 min) and the time for the maximal hybridization between FAM-ssDNA and target DNA to occur (60 min). The detection limits were estimated as 345 pM and 278 pM for the PET/PPY-PANI and PET/PANI-PPY hybrid films, respectively. The simplicity of the procedure, coupled with the fact that a positive/negative response can be obtained in less than 60 min, suggests that the proposal of using these polymeric bilayer films is a promising methodology for the development of rapid molecular diagnostic tests.

6.
J Virol ; : JVI0130121, 2021 Oct 13.
Article in English | MEDLINE | ID: mdl-34643427

ABSTRACT

The ability of viruses to evade the host antiviral immune system determines their level of replication fitness, species specificity, and pathogenic potential. Flaviviruses rely on the subversion of innate immune barriers including the type I and type III IFN antiviral systems. Zika virus infection induces the degradation of STAT2, an essential component of the IFN stimulated gene transcription factor, ISGF3. The mechanisms that lead to STAT2 degradation by Zika virus are poorly understood, but it is known to be mediated by the viral NS5 protein that binds to STAT2 and targets it for proteasome-mediated destruction. To better understand how NS5 engages and degrades STAT2, functional analysis of the protein interactions that lead to Zika virus and NS5-dependent STAT2 proteolysis were investigated. Data implicate the STAT2 coiled-coil domain as necessary and sufficient for NS5 interaction and proteasome degradation after Zika virus infection. Molecular dissection reveals that the first two α-helices of the STAT2 coiled-coil contain a specific targeting region for IFN antagonism. These functional interactions provide a more complete understanding of the essential protein-protein interactions needed for Zika virus evasion of the host antiviral response, and identifies new targets for antiviral therapeutic approaches. Importance Zika virus infection can cause mild fever, rash, and muscle pain, and in rare cases lead to brain or nervous system diseases including Guillain-Barré syndrome. Infections in pregnant women can increase the risk of miscarriage or serious birth defects including brain anomalies and microcephaly. There are no drugs or vaccines for Zika disease. Zika virus is known to break down the host antiviral immune response, and this research project reveals how the virus suppresses interferon signaling, and may reveal therapeutic vulnerabilities.

7.
Sci Rep ; 11(1): 19635, 2021 Oct 04.
Article in English | MEDLINE | ID: mdl-34608212

ABSTRACT

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes febrile illness. The recent spread of ZIKV from Asia to the Americas via the Pacific region has revealed unprecedented features of ZIKV, including transplacental congenital infection causing microcephaly. Amino acid changes have been hypothesized to underlie the spread and novel features of American ZIKV strains; however, the relationship between genetic changes and the epidemic remains controversial. A comparison of the characteristics of a Southeast Asian strain (NIID123) and an American strain (PRVABC59) revealed that the latter had a higher replication ability in cultured cells and higher virulence in mice. In this study, we aimed to identify the genetic region of ZIKV responsible for these different characteristics using reverse genetics. A chimeric NIID123 strain in which the E protein was replaced with that of PRVABC59 showed a lower growth ability than the recombinant wild-type strain. Adaptation of the chimeric NIID123 to Vero cells induced a Phe-to-Leu amino acid substitution at position 146 of the prM protein; PRVABC59 also has Leu at this position. Leu at this position was found to be responsible for the viral replication ability and partially, for the pathogenicity in mouse testes.

8.
Antiviral Res ; : 105188, 2021 Oct 11.
Article in English | MEDLINE | ID: mdl-34648875

ABSTRACT

Zika virus (ZIKV) has been the cause of some epidemics since 2007. The correlations of microcephaly and Guillain-Barré syndrome with ZIKV have been noticed. Unfortunately, researchers have yet to develop an effective vaccine or drug approved for ZIKV infection. Anidulafungin is a member of echinocandins that is used to treat candida infections. This study assessed the antiviral capability of anidulafungin against ZIKV. Anidulafungin was shown to significantly decrease viral RNA levels, protein expression levels, viral yields, and the rate of infection. In time of addition assays, anidulafungin exhibited inhibitory activities in the early stages of ZIKV infection. In binding and entry assays, administering anidulafungin did not lead to a corresponding decrease in quantity of viral RNA, but a significant decrease in ZIKV infectivity was observed in virucidal assays. This indicated that anidulafungin interferes directly with virions. T-1105 is a viral RNA replication inhibitor, which functions in the late stage of ZIKV infection. When anidulafungin was administered in combination with T-1105, an obvious synergistic effect was observed, resulting in a combination index (CI) value of 0.85 ±â€¯0.13. Finally, we evaluated the effects of echinocandins in terms of half-maximal inhibitory concentration (IC50), calculation of cytotoxicity concentration 50% (CC50), selectivity index (SI), and Patchdock score. Among the tests, anidulafungin bears the lowest IC50 and highest Patchdock score. Although anidulafungin is classified as a pregnancy category C agent; however, combination therapy of anidulafungin with a viral RNA replication inhibitor could expand treatment options for ZIKV infection.

9.
Front Cell Neurosci ; 15: 695106, 2021.
Article in English | MEDLINE | ID: mdl-34658789

ABSTRACT

Despite being perceived to be a relatively innocuous pathogen during its circulation in Africa in the 20th century, consequent outbreaks in French Polynesia and Latin America revealed the Zika virus (ZIKV) to be capable of causing severe neurological defects. Foetuses infected with the virus during pregnancy developed a range of pathologies including microcephaly, cerebral calcifications and macular scarring. These are now collectively known as Congenital Zika syndrome (CZS). It has been established that the neuropathogenesis of ZIKV results from infection of neural progenitor cells in the developing cerebral cortex. Following this, two main hypotheses have emerged: the virus causes either apoptosis or premature differentiation of neural progenitor cells, reducing the final number of mature neurons in the cerebral cortex. This review describes the cellular processes which could potentially cause virus induced apoptosis or premature differentiation, leading to speculation that a combination of the two may be responsible for the pathologies associated with ZIKV. The review also discusses which specific lineages of the ZIKV can employ these mechanisms. It has been unclear in the past whether the virus evolved its neurotropic capability following circulation in Africa, or if the virus has always caused microcephaly but public health surveillance in Africa had failed to detect it. Understanding the true neuropathogenesis of ZIKV is key to being prepared for further outbreaks in the future, and it will also provide insight into how neurotropic viruses can cause profound and life-long neurological defects.

10.
RSC Med Chem ; 12(9): 1525-1539, 2021 Sep 23.
Article in English | MEDLINE | ID: mdl-34671736

ABSTRACT

The identification of specific biomarkers for Zika infection and its clinical complications is fundamental to mitigate the infection spread, which has been associated with a broad range of neurological sequelae. We present the characterization of antibody responses in serum samples from individuals infected with Zika, presenting non-severe (classical) and severe (neurological disease) phenotypes, with high-density peptide arrays comprising the Zika NS1 and NS2B proteins. The data pinpoints one strongly IgG-targeted NS2B epitope in non-severe infections, which is absent in Zika patients, where infection progressed to the severe phenotype. This differential IgG profile between the studied groups was confirmed by multivariate data analysis. Molecular dynamics simulations and circular dichroism have shown that the peptide in solution presents itself in a sub-optimal conformation for antibody recognition, which led us to computationally engineer an artificial protein able to stabilize the NS2B epitope structure. The engineered protein was used to interrogate paired samples from mothers and their babies presenting Zika-associated microcephaly and confirmed the absence of NS2B IgG response in those samples. These findings suggest that the assessment of antibody responses to the herein identified NS2B epitope is a strong candidate biomarker for the diagnosis and prognosis of Zika-associated neurological disease.

11.
Braz J Infect Dis ; 25(5): 101629, 2021 Oct 08.
Article in English | MEDLINE | ID: mdl-34627783

ABSTRACT

BACKGROUND: The recognition of the causal association between Zika virus (ZIKV) infection during pregnancy and congenital abnormalities including microcephaly underlines the importance of preventing this disease in pregnant women (PW) and women of childbearing age (WCA). Although Brazil and other Latin American countries reported a significant reduction in the number of ZIKV infections in recent years, epidemic waves can recur in settings with previous outbreaks as conditions for transmission remain optimal and susceptible populations are continuously replenished. METHODS: In this cross-sectional study, we enrolled 64 PW and 260 non-pregnant WCA attending routine medical appointments in two primary care units in Sao Paulo, Brazil, and assessed knowledge and attitudes about ZIKV infection and prevention. RESULTS: Most women reported knowing that ZIKV is transmitted through the bite of Aedes mosquitos, and most knew that acute symptoms are similar to those seen in Dengue infection. Furthermore, most participants correctly described that ZIKV infection during pregnancy may cause detrimental outcomes for the newborn. However, most ignored that ZIKV infection can be asymptomatic, and only 15% knew about the risk of ZIKV sexual transmission. We found no statistically significant differences between PW and WCA regarding knowledge about ZIKV sexual transmission. Knowledge about ZIKV sexual transmission was significantly associated with education; among participants with ≤12 schooling years, only 9.0% (95%CI 3.4-18.5%) correctly answered that ZIKV can be sexually transmitted, compared to 12.9% (95%CI 8.2-18.8%) among participants with 12-14 schooling years, and to 24.4% (95%CI 15.9-34.9%) of participants with ≥15 schooling years (p = 0.015). Education remained independently associated with knowledge about sexual transmission of ZIKV in a multivariate logistic regression model adjusted for age, race and pregnancy status (p = 0.022). CONCLUSION: Our findings underscore the urgent need of educational and family planning programs that may help prevent detrimental outcomes of ZIKV infection in an endemic area of Brazil.

12.
Virus Res ; 306: 198593, 2021 Oct 09.
Article in English | MEDLINE | ID: mdl-34637814

ABSTRACT

Zika virus (ZIKV) is a typical mosquito-borne flavivirus known to cause severe fetal microcephaly and adult Guillain-Barré syndrome. Currently, there are no specific drugs or licensed vaccines available for ZIKV infection, and further research is required to identify host cell proteins involved in the virus's life cycle. Viruses are known to use host cell membrane skeletal proteins, such as actin and spectrin, to complete cell entry, transportation, and release. Here, based on immunoprecipitation, the Axl and ZIKV envelope (E) protein were shown to interact with the cell membrane skeleton protein 4.1R. Furthermore, deletion of 4.1R significantly reduced virus titer and viral protein synthesis. Our study showed that 4.1R is an important host cell protein during ZIKV infection and may be involved in the process of viral entry into host cells.

13.
Proteomics Clin Appl ; : e2100041, 2021 Oct 21.
Article in English | MEDLINE | ID: mdl-34676661

ABSTRACT

During pregnancy, the vertical transmission of the Zika virus (ZIKV) can cause some disorders in the fetus, called Congenital Zika Syndrome (CZS). Several efforts have been made to understand the molecular mechanism of the CZS. However, the study of CZS pathogenesis through infected human samples is scarce. Therefore, the main goal of this study is to identify and understand the biological processes affected by CZS development. We analyzed by a shotgun proteomic approach the amniotic fluid of pregnant women infected with Zika carrying microcephalic (MC+ ) or non-microcephalic (Z+ ) compared to Zika negative controls (CTR). Several groups of extracellular matrix (ECM) proteins were dysregulated in the Z+ and MC+ patients, triggering an opposite dysregulation. The down-regulation of the ECM proteins in the MC+ groups can be another factor that contributes to CZS. On the contrary, the Z+ group could be developing a neuroprotective response through ECM proteins up-regulation. The neutrophil degranulation process was disrupted in the Z+ and MC+ groups, where the MC+ groups showed a complex dysregulation. These results suggest that the microcephalic phenotypes are modulated by a down-regulation of the ECM and the impairment of the innate immune system processes. This article is protected by copyright. All rights reserved.

14.
Eur J Obstet Gynecol Reprod Biol ; 265: 162-168, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34508989

ABSTRACT

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) transmitted primarily by Aedes mosquitoes. ZIKV can be transmitted to humans by non-vector borne mechanisms such as sexual intercourse, maternal-foetal transmission or blood transfusion. In 2015, ZIKV emerged in the Americas, and spread to 87 countries and territories with autochthonous transmission, distributed across four of the six WHO regions. Most ZIKV infections in pregnancy are asymptomatic, but mother to child transmission of the virus can occur in 20 to 30% of cases and cause severe foetal and child defects. Children exposed to ZIKV while in utero might develop a pattern of structural anomalies and functional disabilities secondary to central nervous system damage, known as congenital Zika syndrome, and whose most common clinical feature is microcephaly. Normocephalic children born to mothers with ZIKV infection in pregnancy, and with no observable Zika-associated birth defects, may also present with later neurodevelopmental delay or post-natal microcephaly. Screening and detection of ZIKV infection in pregnancy is essential, because most women with ZIKV infection are asymptomatic and clinical manifestations are non-specific. However, the diagnosis of ZIKV infection poses multiple challenges due to limited resources and scarce laboratory capabilities in most affected areas, the narrow window of time that the virus persists in the bloodstream, the large proportion of asymptomatic infections, and the cross-reactivity with other flaviviruses such as Dengue virus (DENV). Molecular methods (RT-PCR) are the most reliable tool to confirm ZIKV infection, as serodiagnosis requires confirmation with neutralization tests in case of inconclusive or positive serology results. Prenatal ultrasound assessment is essential for monitoring foetal development and early detection of possible severe anomalies. A mid- and long-term follow-up of children exposed to ZIKV while in utero is necessary to promptly detect clinical manifestations of possible neurological impairment. Tweetable abstract: Zika virus infection during pregnancy is a cause of pregnancy loss and disability in children. Protection against mosquito bites, access to sexual and reproductive health services, prompt screening and detection of ZIKV infection in pregnancy, and prenatal ultrasound monitoring are key control strategies whilst a vaccine is not available.


Subject(s)
Pregnancy Complications, Infectious , Zika Virus Infection , Zika Virus , Animals , Child , Female , Humans , Infectious Disease Transmission, Vertical , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnant Women , Zika Virus Infection/complications , Zika Virus Infection/diagnosis , Zika Virus Infection/epidemiology
15.
Med Hypotheses ; 156: 110685, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34592564

ABSTRACT

Zika virus was declared a national emergency by WHO (World Health Organization) in 2016 when its widespread outbreaks and life-threatening complications were reported, especially in newborns and adults. Numerous studies reported that neuroinflammation is one of the significant root-causes behind its major neurological complications like microcephaly and Guillain-Barré syndrome (GBS). In this hypothesis, we propose Transient Receptor Potential Vanilloid 1 channel (TRPV1) as a major culprit in triggering positive inflammatory loop, ultimately leading to sustained neuroinflammation, one of the key clinical findings in Zika induced microcephalic and GBS patients. Opening of TRPV1 channel also leads to calcium influx and oxidative stress that ultimately results in cellular apoptosis (like Schwann cell in GBS and developing fetal nerve cells in microcephaly), ultimately leading to these complications. Currently, no specific cure exists for these complications. Most of the antiviral candidates are under clinical trials. Though there is no direct research on TRPV1 as a cause of Zika virus's neurological complications, but similarity in mechanisms is undeniable. Thus, exploring pathobiological involvement of TRPV1 channels and various TRPV1 modulators in these complications can possibly prove to be an effective futuristic therapeutic strategy for treatment and management of these life-threatening complications.


Subject(s)
Microcephaly , Nervous System Diseases , Zika Virus Infection , Zika Virus , Calcium/metabolism , Capsaicin , Humans , Infant, Newborn , Nervous System Diseases/drug therapy , Neurons/metabolism , TRPV Cation Channels , Zika Virus/metabolism , Zika Virus Infection/complications , Zika Virus Infection/drug therapy
16.
Int J Biol Macromol ; 190: 713-721, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34474053

ABSTRACT

Zika virus (ZIKV) induces neurological and autoimmune complications such as microcephaly and Guillain-Barre syndrome. Effective vaccines are necessary to prevent the ZIKV infection. E protein of ZIKV is responsible for virus attachment, entry, and fusion. The domain III of E protein (EDIII) contains the neutralizing epitopes and is ideal to act as an antigen for ZIKV vaccine. However, EDIII is poorly immunogenic. CRM197 is a carrier protein and can activate T helper cells for EDIII. Mannan is a ligand of TLR-4 or TLR-2. Eight-arm PEG can link multiple EDIII molecules in one entity. In the present study, EDIII was covalently conjugated with CRM197, 8-arm PEG and mannan to improve the immunogenicity of EDIII. The conjugate (CRM-EDIII-PM) elicited high EDIII-specific antibody titers in the BALB/c mice. Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-5 and IL-10) were secreted at a marked level. Thus, CRM-EDIII-PM could stimulate potent humoral and cellular immune response to EDIII. The serum exposure of CRM-EDIII-PM to the immune system was prolonged. Moreover, CRM-EDIII-PM did not lead to apparent toxicity to the organs. Therefore, CRM-EDIII-PM was expected as a promising vaccine candidate for its ability to induce strong immune responses.

17.
Sci Rep ; 11(1): 19270, 2021 Sep 29.
Article in English | MEDLINE | ID: mdl-34588470

ABSTRACT

Congenital Zika Syndrome (CZS) is characterized by changes in cranial morphology associated with heterogeneous neurological manifestations and cognitive and behavioral impairments. In this syndrome, longitudinal neuroimaging could help clinicians to predict developmental trajectories of children and tailor treatment plans accordingly. However, regularly acquiring magnetic resonance imaging (MRI) has several shortcomings besides cost, particularly those associated with childrens' clinical presentation as sensitivity to environmental stimuli. The indirect monitoring of local neural activity by non-invasive functional near-infrared spectroscopy (fNIRS) technique can be a useful alternative for longitudinally accessing the brain function in children with CZS. In order to provide a common framework for advancing longitudinal neuroimaging assessment, we propose a principled guideline for fNIRS acquisition and analyses in children with neurodevelopmental disorders. Based on our experience on collecting fNIRS data in children with CZS we emphasize the methodological challenges, such as clinical characteristics of the sample, desensitization, movement artifacts and environment control, as well as suggestions for tackling such challenges. Finally, metrics based on fNIRS can be associated with established clinical metrics, thereby opening possibilities for exploring this tool as a long-term predictor when assessing the effectiveness of treatments aimed at children with severe neurodevelopmental disorders.

18.
Cad Saude Publica ; 37(8): e00271020, 2021.
Article in Portuguese | MEDLINE | ID: mdl-34495097

ABSTRACT

This study aimed to assess the degree of implementation of the response to the emergency of microcephaly associated with Zika virus in Pernambuco State, Brazil. This was a normative evaluative study conducted in the initial epicenter of the public health emergency of international concern, from October 2015 to July 2017. A logical model was produced for the intervention under analysis, with the components of Management, Surveillance, and Care in the dimensions of structure, process, and result, based on technical publications and institutional guidelines, in addition to a corresponding log frame of indicators for assessment. Data were collected through a questionnaire, direct observation, and consultation of official documents. The results showed partial implementation (74.9%) of the response to the microcephaly emergency by the Pernambuco State Health Department, with the process dimension reaching 75% of the expected level and the structure dimension, 74.5%. Surveillance was the only component that was assessed as implemented (81%), although with a shortage of regional and laboratory investments, while Management (74.2%) and Care (68.8%) were partially implemented, with insufficiencies in items related to human resources and physical structure, planning, and evaluation. In conclusion, the response to the public health emergency of international concern involving microcephaly associated with the Zika virus was assessed as partially implemented, with different levels between the intervention´s components, especially surveillance when compared to management and care. The shortcomings signal the need for investments to deal with future public health emergencies, with a view towards more timely and adequate interventions.


Subject(s)
Microcephaly , Zika Virus Infection , Zika Virus , Brazil/epidemiology , Emergencies , Humans , Microcephaly/epidemiology , Public Health , Zika Virus Infection/diagnosis , Zika Virus Infection/epidemiology
19.
Viruses ; 13(9)2021 Sep 05.
Article in English | MEDLINE | ID: mdl-34578352

ABSTRACT

Infection with Zika virus (ZIKV), a member of the Flavivirus genus of the Flaviviridae family, typically results in mild self-limited illness, but severe neurological disease occurs in a limited subset of patients. In contrast, serious outcomes commonly occur in pregnancy that affect the developing fetus, including microcephaly and other major birth defects. The genetic similarity of ZIKV to other widespread flaviviruses, such as dengue virus (DENV), presents a challenge to the development of specific ZIKV diagnostic assays. Nonstructural protein 1 (NS1) is established for use in immunodiagnostic assays for flaviviruses. To address the cross-reactivity of ZIKV NS1 with proteins from other flaviviruses we used site-directed mutagenesis to modify putative epitopes. Goat polyclonal antibodies to variant ZIKV NS1 were affinity-purified to remove antibodies binding to the closely related NS1 protein of DENV. An antigen-capture ELISA configured with the affinity-purified polyclonal antibody showed a linear dynamic range between approximately 500 and 30 ng/mL, with a limit of detection of between 1.95 and 7.8 ng/mL. NS1 proteins from DENV, yellow fever virus, St. Louis encephalitis virus and West Nile virus showed significantly reduced reactivity in the ZIKV antigen-capture ELISA. Refinement of approaches similar to those employed here could lead to development of ZIKV-specific immunoassays suitable for use in areas where infections with related flaviviruses are common.

20.
Viruses ; 13(9)2021 Sep 10.
Article in English | MEDLINE | ID: mdl-34578383

ABSTRACT

Zika virus (ZIKV) is the mosquito-transmitted virus that the WHO declared a Public Health Emergency of International Concern in 2016 due to the consequence of microcephaly from infected pregnancies. The incidence of Zika infection has been unclear in many countries because most infected people have nonspecific febrile illnesses. This study's aim is to investigate the incidence of symptomatic Zika virus infections from the archived samples of a dengue cohort study of children in central Thailand from 2006 to 2009. We performed Zika NS1 immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) screening to identify symptomatic Zika infections in paired acute/convalescent serum samples. Symptomatic Zika infections were confirmed by reverse transcription polymerase chain reactions (RT-PCR) of acute serum samples. The comparison of the Zika NS1 IgG ELISA results between acute and convalescent samples showed 290/955 (30.4%) seropositive cases. Zika RT-PCR results were positive in 28 febrile cases (15 females, 13 males). Zika RT-PCR showed that symptomatic Zika infection occurred in children aged 4-11 years in Ratchaburi province, Thailand (2007-2009, first case in April 2007), and the symptomatic Zika:dengue infection ratio was 28 Zika:394 dengue (1:14). Phylogenetic analysis showed that all Zika viruses were of Asian lineage. Zika NS1 IgG ELISA identified Zika-infected patients and showed a low Zika:dengue ratio.

SELECTION OF CITATIONS
SEARCH DETAIL
...