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1.
J Pediatr ; 2022 May 13.
Article in English | MEDLINE | ID: mdl-35577118

ABSTRACT

OBJECTIVE: To describe anthropometric, sensory, and neurodevelopmental outcomes of Zika virus exposed children from birth to 36 months. STUDY DESIGN: The cohort includes 114 children born to mothers with confirmed and probable ZIKV pregnancy infection, from 2016-2017. Children attending study visits from May 2017 through February 2020 underwent physical/neurologic, sensory examinations, and neurodevelopmental assessments with Bayley Scales of Infant and Toddler Development (BSID-III) and Ages and Stages Questionnaires (ASQ-3). RESULTS: Three of 114 (2.6%) children had microcephaly (z score < -2) at birth, 19 of 35 (54.3%) had posterior eye abnormalities in retinal image, and 11 of 109 (10.1%) had nonspecific findings on brain ultrasound. Three of 107 (2.8%) failed hearing screening at birth. Of those with follow up, 17 of 97 (17.5%) failed age-appropriate vision screening; BSID-III identified developmental delay in at least one domain in at least one-third of children, with higher prevalence in the language domain. ASQ-3 screen positive delay peaked around 24 or 36 months, some domains showing decrease at older ages. Correlations were observed among BSID-III and ASQ-3 scores, representing professional and parental perspectives at 24 and 36 months (r = 0.32 to 0.78 p<.05). CONCLUSION: The presence of neurodevelopmental sequelae in early childhood suggests that identification of long-term impairment remains critical to attaining optimal child development. Long-term follow up highlights vulnerability in the language domain, which likely could be influenced by early intervention, promoting cognitive development and school readiness among exposed children.

2.
Cad Saude Publica ; 38(4): e00104221, 2022.
Article in English | MEDLINE | ID: mdl-35508028

ABSTRACT

This article uses a socio-anthropological framework to explore the stigmas around interactions with children born with congenital Zika syndrome caused by the Zika virus epidemic in two Brazilian municipalities. Semi-structured interviews were conducted with parents and other relatives. We reflected on the search for meaning when having a baby with unexpected body marks, the moral suffering, the societal ableism, the burden of care, and the need for support networks. We concluded that public policies, especially social policies (health, education, and social assistance), are essential for compensatory mechanisms, recognition, and social inclusion of these children and their families.


Subject(s)
Epidemics , Microcephaly , Zika Virus Infection , Zika Virus , Brazil/epidemiology , Child , Humans , Infant , Microcephaly/epidemiology , Microcephaly/etiology , Social Stigma , Zika Virus Infection/epidemiology
3.
Disaster Med Public Health Prep ; : 1-8, 2022 Apr 11.
Article in English | MEDLINE | ID: mdl-35400356

ABSTRACT

OBJECTIVE: The aim of this study is to assess knowledge and attitudes toward Zika virus disease (ZVD) as well as mosquito prevention practices in Malaysia at a nationwide level. METHODS: Computer-assisted telephone interviews (CATI) were conducted between June 2019 and February 2020. RESULTS: There are gaps in knowledge about the symptoms, mode of transmission, and risk of microcephaly. The mean for the Zika-related knowledge score was 5.9 (SD ± 4.4) out of a possible score of 14. The majority perceived little or no risk of getting ZVD (75.0%) and 75.5% were a little or not at all worried about ZVD. A high proportion reported the use of insect sprays or mosquito coils to prevent mosquito bites; however, a relatively lower proportion of people reported fixing mosquito netting on doors and windows, and using mosquito bed nets. The mean for the mosquito prevention practices score was 11.9 (SD ± 4.7) out of a possible score of 27. Important factors influencing mosquito prevention practices include household income, environment factors, risk perception, and Zika-related knowledge. CONCLUSION: Zika prevention measures should be targeted in priority toward residents in lower socioeconomic neighborhoods. Campaigns should focus on messages highlighting the high risk of getting dengue.

4.
Am J Trop Med Hyg ; 2022 Apr 11.
Article in English | MEDLINE | ID: mdl-35405646

ABSTRACT

Co-circulation of arthropod-borne viruses, particularly those with shared mosquito vectors like Zika (ZIKV) and Chikungunya (CHIKV), is increasingly reported. An accurate differential diagnosis between ZIKV and CHIKV is of high clinical importance, especially in the context of pregnancy, but remains challenging due to limitations in the availability of specialized laboratory testing facilities. Using data collected from the prospective pregnancy cohort study of the Microcephaly Epidemic Research Group, which followed up pregnant persons with rash during the peak and decline of the 2015-2017 ZIKV epidemic in Recife, Pernambuco, Brazil, this study aims to describe the geographic and temporal distribution of ZIKV and CHIKV infections and to investigate the extent to which ZIKV and CHIKV infections may be clinically differentiable. Between December 2015 and June 2017, we observed evidence of co-circulation with laboratory confirmation of 213 ZIKV mono-infections, 55 CHIKV mono-infections, and 58 sequential ZIKV/CHIKV infections (i.e., cases with evidence of acute ZIKV infection with concomitant serological evidence of recent CHIKV infection). In logistic regressions with adjustment for maternal age, ZIKV mono-infected cases had lower odds than CHIKV mono-infected cases of presenting with arthralgia (aOR, 99% CI: 0.33, 0.15-0.74), arthritis (0.35, 0.14-0.85), fatigue (0.40, 0.17-0.96), and headache (0.44, 0.19-1.90). However, sequential ZIKV/CHIKV infections complicated discrimination, as they did not significantly differ in clinical presentation from CHIKV mono-infections. These findings suggest clinical symptoms alone may be insufficient for differentiating between ZIKV and CHIKV infections during pregnancy and therefore laboratory diagnostics continue to be a valuable tool for tailoring care in the event of arboviral co-circulation.

5.
Front Immunol ; 13: 773191, 2022.
Article in English | MEDLINE | ID: mdl-35371036

ABSTRACT

Zika virus (ZIKV), despite being discovered six decades earlier, became a major health concern only after an epidemic in French Polynesia and an increase in the number of microcephaly cases in Brazil. Substantial evidence has been found to support the link between ZIKV and neurological complications in infants. The virus targets various cells in the brain, including radial glial cells, neural progenitor cells (NPCs), astrocytes, microglial and glioblastoma stem cells. It affects the brain cells by exploiting different mechanisms, mainly through apoptosis and cell cycle dysregulation. The modulation of host immune response and the inflammatory process has also been demonstrated to play a critical role in ZIKV induced neurological complications. In addition to that, different ZIKV strains have exhibited specific neurotropism and unique molecular mechanisms. This review provides a comprehensive and up-to-date overview of ZIKV-induced neuroimmunopathogenesis by dissecting its main target cells in the brain, and the underlying cellular and molecular mechanisms. We highlighted the roles of the different ZIKV host factors and how they exploit specific host factors through various mechanisms. Overall, it covers key components for understanding the crosstalk between ZIKV and the brain.


Subject(s)
Microcephaly , Nervous System Diseases , Neural Stem Cells , Zika Virus Infection , Zika Virus , Brain/pathology , Humans , Microcephaly/pathology , Nervous System Diseases/pathology , Neural Stem Cells/pathology , Zika Virus/physiology
6.
J Neuroinflammation ; 19(1): 100, 2022 Apr 24.
Article in English | MEDLINE | ID: mdl-35462541

ABSTRACT

BACKGROUND: Zika virus (ZIKV) is an emerging flavivirus of global concern. ZIKV infection of the central nervous system has been linked to a variety of clinical syndromes, including microcephaly in fetuses and rare but serious neurologic disease in adults. However, the potential for ZIKV to influence brain physiology and host behavior following apparently mild or subclinical infection is less well understood. Furthermore, though deficits in cognitive function are well-documented after recovery from neuroinvasive viral infection, the potential impact of ZIKV on other host behavioral domains has not been thoroughly explored. METHODS: We used transcriptomic profiling, including unbiased gene ontology enrichment analysis, to assess the impact of ZIKV infection on gene expression in primary cortical neuron cultures. These studies were extended with molecular biological analysis of gene expression and inflammatory cytokine signaling. In vitro observations were further confirmed using established in vivo models of ZIKV infection in immunocompetent hosts. RESULTS: Transcriptomic profiling of primary neuron cultures following ZIKV infection revealed altered expression of key genes associated with major psychiatric disorders, such as bipolar disorder and schizophrenia. Gene ontology enrichment analysis also revealed significant changes in gene expression associated with fundamental neurobiological processes, including neuronal development, neurotransmission, and others. These alterations to neurologic gene expression were also observed in the brain in vivo using several immunocompetent mouse models of ZIKV infection. Mechanistic studies identified TNF-α signaling via TNFR1 as a major regulatory mechanism controlling ZIKV-induced changes to neurologic gene expression. CONCLUSIONS: Our studies reveal that cell-intrinsic innate immune responses to ZIKV infection profoundly shape neuronal transcriptional profiles, highlighting the need to further explore associations between ZIKV infection and disordered host behavioral states.


Subject(s)
Mental Disorders , Zika Virus Infection , Zika Virus , Animals , Humans , Mental Disorders/etiology , Mental Disorders/genetics , Mental Disorders/metabolism , Mental Disorders/virology , Mice , Receptors, Tumor Necrosis Factor, Type I/genetics , Receptors, Tumor Necrosis Factor, Type I/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , Virus Replication/physiology , Zika Virus Infection/complications , Zika Virus Infection/genetics , Zika Virus Infection/metabolism
7.
PLoS One ; 17(4): e0257408, 2022.
Article in English | MEDLINE | ID: mdl-35446851

ABSTRACT

Zika virus (ZIKV) is a positive-sense RNA flavivirus and can cause serious neurological disorders including microcephaly in infected fetuses. As a mosquito-borne arbovirus, it enters the bloodstream and replicates in various organs. During pregnancy, it can be transmitted from the blood of the viremic mother to the fetus by crossing the placental barrier. Monocytes and macrophages are considered the earliest blood cell types to be infected by ZIKV. As a first line defense, these cells are crucial components in innate immunity and host responses and may impact viral pathogenesis in humans. Previous studies have shown that ZIKV infection can activate inflammasomes and induce proinflammatory cytokines in monocytes. In this report, we showed that ZIKV could infect and induce cell death in human and murine macrophages. In addition to the presence of cleaved caspase-3, indicating that apoptosis was involved, we identified the cleaved caspase-1 and gasdermin D (GSDMD) as well as increased secretion of IL-1ß and IL-18. This suggests that the inflammasome was activated and that may lead to pyroptosis in infected macrophages. The pyroptosis was NLRP3-dependent and could be suppressed in the macrophages treated with shRNA to target and knockdown caspase-1. It was also be inhibited by an inhibitor for caspase-1, indicating that the pyroptosis was triggered via a canonical approach. Our findings in this study demonstrate a concomitant occurrence of apoptosis and pyroptosis in ZIKV-infected macrophages, with two mechanisms involved in the cell death, which may have potentially significant impacts on viral pathogenesis in humans.


Subject(s)
Zika Virus Infection , Zika Virus , Animals , Apoptosis , Caspase 1/metabolism , Female , Humans , Inflammasomes/metabolism , Interleukin-1beta/metabolism , Macrophages/metabolism , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Placenta/metabolism , Pregnancy , Pyroptosis , Zika Virus/metabolism , Zika Virus Infection/metabolism
8.
Oral Dis ; 2022 Apr 29.
Article in English | MEDLINE | ID: mdl-35485177

ABSTRACT

OBJECTIVE: to investigate the impact of the severity of microcephaly caused by the Zika virus (MCZ) on tooth eruption and orofacial structures of children. DESIGN: This case series study developed the research at the Mens Sana Rehabilitation Center, Arcoverde, Brazil. The study included 27 children diagnosed with MCZ. We performed the data collection in June 2018 through a questionnaire answered by the legal guardians, followed by a clinical examination of the children. The data were analyzed by the Mann-Whitney and Fisher's exact tests (p = 0.05). RESULTS: The final sample was composed of 20 children. Of these, 13 (35.0%) had severe microcephaly, 5 (30.0%) had altered sequence of tooth eruption, 10 (50.0%) had delayed eruption, and the mean number of decayed teeth was 2.3. The most identified orofacial changes were teeth grinding habit (65.0%), difficult chewing (50.0%), and non-nutritive sucking (50.0%). The Mann-Whitney test showed that the severity of microcephaly did not affect tooth eruption (p = 0.581). The Fisher's exact test showed that the severity of microcephaly was not associated with orofacial changes (p > 0.05). CONCLUSIONS: The severity of MCZ does not seem to influence changes in deciduous tooth eruption and the presence of orofacial anomalies.

9.
Int J Infect Dis ; 120: 201-204, 2022 Apr 22.
Article in English | MEDLINE | ID: mdl-35470025

ABSTRACT

OBJECTIVES: To describe the differences in clinical presentation and relative disease burden of congenital Zika syndrome (CZS)-associated microcephaly at 2 large hospitals in Salvador, Brazil that serve patients of different socioeconomic status (SES). METHODS: Clinical and serologic data were collected prospectively from pregnant women and their infants, who delivered at 2 study centers during the 2015-2016 Zika virus (ZIKV) epidemic in Salvador, Brazil. RESULTS: Pregnant women from Salvador, Brazil delivering in a low SES hospital had 3 times higher ZIKV exposure rate than women at a high SES hospital. However, different SES hospitals had similar prevalence of infants with CZS-associated microcephaly (10% vs 6%, p = 0.16) after controlling for ZIKV exposure in their mothers. CONCLUSIONS: Our study supports the positive association between low SES, high maternal ZIKV exposure, and high rates of CZS-associated microcephaly.

10.
Antiviral Res ; 202: 105313, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35367280

ABSTRACT

After decades of being considered non-pathogenic, Zika virus (ZIKV) emerged as an important threat to human health during the epidemic of 2015-2016. ZIKV infections are usually asymptomatic, but can cause Guillain-Barré syndrome in adults and microcephaly in newborns. As there are currently no approved antiviral drugs against ZIKV, we tested anti-ZIKV activity of compounds from the NIH Clinical Collection for which we previously showed antiviral activity against the related dengue virus. One of the top hits from the screen was lacidipine, a 1,4-dihydropyridine calcium antagonist that is approved as an antihypertensive drug. Our data show that lacidipine is antiviral against ZIKV (strain H/PF/2013) in both Vero cells and induced pluripotent stem cell (iPSC)-derived human neural progenitor cells with IC50 values of 3.0 µM and <50 nM, respectively. The antiviral effect was also observed against four other ZIKV strains from the African and Asian lineages. Time-of-addition and replicon assays indicated that lacidipine acts at the post-entry stage of the viral replication cycle, inhibiting viral genome replication. Lacidipine altered the subcellular distribution of free cholesterol and neutral lipids, suggesting that the antiviral effect of lacidipine is mediated by altered trafficking of lipids. Together, these results identify lacidipine as a novel inhibitor of ZIKV replication that likely disturbs trafficking of lipids needed for replication organelle formation.

11.
J Virol ; 96(9): e0033322, 2022 May 11.
Article in English | MEDLINE | ID: mdl-35412344

ABSTRACT

Vertical transmission of Zika virus (ZIKV) leads with high frequency to congenital ZIKV syndrome (CZS), whose worst outcome is microcephaly. However, the mechanisms of congenital ZIKV neurodevelopmental pathologies, including direct cytotoxicity to neural progenitor cells (NPC), placental insufficiency, and immune responses, remain incompletely understood. At the cellular level, microcephaly typically results from death or insufficient proliferation of NPC or cortical neurons. NPC replicate fast, requiring efficient DNA damage responses to ensure genome stability. Like congenital ZIKV infection, mutations in the polynucleotide 5'-kinase 3'-phosphatase (PNKP) gene, which encodes a critical DNA damage repair enzyme, result in recessive syndromes often characterized by congenital microcephaly with seizures (MCSZ). We thus tested whether there were any links between ZIKV and PNKP. Here, we show that two PNKP phosphatase inhibitors or PNKP knockout inhibited ZIKV replication. PNKP relocalized from the nucleus to the cytoplasm in infected cells, colocalizing with the marker of ZIKV replication factories (RF) NS1 and resulting in functional nuclear PNKP depletion. Although infected NPC accumulated DNA damage, they failed to activate the DNA damage checkpoint kinases Chk1 and Chk2. ZIKV also induced activation of cytoplasmic CycA/CDK1 complexes, which trigger unscheduled mitotic entry. Inhibition of CDK1 activity inhibited ZIKV replication and the formation of RF, supporting a role of cytoplasmic CycA/CDK1 in RF morphogenesis. In brief, ZIKV infection induces mitotic catastrophe resulting from unscheduled mitotic entry in the presence of DNA damage. PNKP and CycA/CDK1 are thus host factors participating in ZIKV replication in NPC, and pathogenesis to neural progenitor cells. IMPORTANCE The 2015-2017 Zika virus (ZIKV) outbreak in Brazil and subsequent international epidemic revealed the strong association between ZIKV infection and congenital malformations, mostly neurodevelopmental defects up to microcephaly. The scale and global expansion of the epidemic, the new ZIKV outbreaks (Kerala state, India, 2021), and the potential burden of future ones pose a serious ongoing risk. However, the cellular and molecular mechanisms resulting in microcephaly remain incompletely understood. Here, we show that ZIKV infection of neuronal progenitor cells results in cytoplasmic sequestration of an essential DNA repair protein itself associated with microcephaly, with the consequent accumulation of DNA damage, together with an unscheduled activation of cytoplasmic CDK1/Cyclin A complexes in the presence of DNA damage. These alterations result in mitotic catastrophe of neuronal progenitors, which would lead to a depletion of cortical neurons during development.

12.
Sex Reprod Healthc ; 32: 100722, 2022 Mar 31.
Article in English | MEDLINE | ID: mdl-35381437

ABSTRACT

BACKGROUND: In 2016, a Public Health Emergency of International Concern (PHEIC) was declared in response to the rise of microcephaly cases among newborns in Northeastern Brazil. A common reactionary measure by public health authorities was to recommend women postpone pregnancy to avoid the possible perinatal transmission of Zika virus (ZIKV). METHODS: The purpose of this study was to assess how women in Fortaleza, Brazil conceptualize pregnancy; experience facilitators and barriers to pregnancy avoidance; perceive the authorities' recommendation to postpone pregnancy due to the ZIKV outbreak; and recall their experiences during the ZIKV epidemic. Qualitative methods, specifically a Rapid Anthropological Assessment (RAA), were utilized in this study. Data collection included semi-structured interviews, triangulated with observations and informal interviews with community members. RESULTS: The sample included 35 women (18-39 years old) who exclusively utilized the national public health care system. Findings indicated that all participants perceived the ZIKV pregnancy-postponement recommendation to be counter-cultural to Brazilian social norms. Overall women's self-perceived agency to prevent pregnancy was low due to social expectations and lack of trust for contraceptives. ZIKV prevention was not seen as a reason to utilize contraceptives. Interestingly, only women who self-perceived as more affluent were willing to attempt pregnancy prevention for educational, occupational, or financial opportunity. CONCLUSION: Pregnancy postponement as a response to a ZIKV epidemic ignores gaps in reproductive agency and defies social norms, making it unrealistic and counter-cultural. Future ZIKV health recommendations must be culturally aligned with the population, and address barriers and motivators for family planning.

13.
Trop Med Int Health ; 2022 Apr 19.
Article in English | MEDLINE | ID: mdl-35441418

ABSTRACT

OBJECTIVE: To describe the urological outcomes in children with congenital Zika syndrome (CZS) and investigate the relationship between clinical and urological findings in this population. METHODS: This cross-sectional study involved children with CZS followed up by a referral center for children with microcephaly in the state of Paraiba in northeast Brazil. Urological evaluation included clinical history, urine culture results, ultrasonography of the urinary tract, and urodynamic evaluation, following the protocol proposed by Costa Monteiro et al. (2017). Descriptive statistical analysis was performed in addition to association and correlation tests, considering clinical and urodynamic variables. RESULTS: Among the 88 children with CZS (35.5±5.5 months), 97.7% had microcephaly and 51% presented urinary tract infection (UTI) confirmed with clinical history and lab tests. The number of confirmed UTI episodes varied from one to 14 per child. Urodynamic evaluation confirmed the presence of an overactive bladder in 78 children and incomplete voiding in 50. Urodynamic findings were associated with the number of confirmed UTI episodes, child's sex, and actual weight, in addition to the use of anticonvulsant and myorelaxant drugs. CONCLUSIONS: UTIs were confirmed in most children. Other urological outcomes observed were overactive bladder and low bladder capacity, which were associated with the number of confirmed UTI episodes, use of anticonvulsants and myorelaxants, and the child's sex and weight. These are treatable conditions, and it is paramount that pediatricians, neonatologists, and infection disease specialists are aware of them to make clinical decisions and help reduce the risk of renal damage and other morbidities.

14.
PLoS Negl Trop Dis ; 16(4): e0010328, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35436298

ABSTRACT

BACKGROUND: The epidemic of Zika virus (ZIKV) was associated with a sudden and unprecedented increase in infants born with microcephaly. Colombia was the second most affected country by the epidemic in the Americas. Primary caregivers of children with ZIKV-associated microcephaly, their mothers mainly, were at higher risk of suffering anxiety and depression. Often, these women were stigmatized and abandoned by their partners, relatives, and communities. METHODOLOGY/PRINCIPAL FINDINGS: This study aimed to understand the perceptions about ZIKV infection among mothers of children born with microcephaly during the ZIKV epidemic in Caribbean Colombia, and the barriers and facilitators affecting child health follow-up. An exploratory qualitative study, based on Phenomenology and Grounded Theory, was conducted in Caribbean Colombia. Data were collected through In-Depth Interviews (IDI) from women who delivered a baby with microcephaly during the ZIKV epidemic at Clínica Salud Social, Sincelejo, Sucre District (N = 11). The themes that emerged during the interviews included experiences from their lives before pregnancy; knowledge about ZIKV; experiences and perceptions when diagnosed; considering a possible termination of pregnancy, and children's clinical follow-up. In some cases, women reported having been told they were having a baby with microcephaly but decided not to terminate the pregnancy; while in other cases, women found out about their newborn's microcephaly condition only at birth. The main barriers encountered by participants during children's follow-up included the lack of psychosocial and economic support, the stigmatization and abandonment by some partners and relatives, and the frustration of seeing the impaired development of their children. CONCLUSIONS: This study contributed to identifying the social, medical, psychological, and economic needs of families with children affected by the ZIKV epidemic. Commitment and action by local and national governments, and international bodies, is required to ensure sustained and quality health services by affected children and their families.


Subject(s)
Microcephaly , Pregnancy Complications, Infectious , Zika Virus Infection , Zika Virus , Anger , Brazil , Child , Colombia/epidemiology , Female , Humans , Infant , Infant, Newborn , Microcephaly/epidemiology , Mothers , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Zika Virus Infection/complications , Zika Virus Infection/diagnosis , Zika Virus Infection/epidemiology
15.
Pharmaceutics ; 14(4)2022 Mar 29.
Article in English | MEDLINE | ID: mdl-35456572

ABSTRACT

Viral disease outbreaks affect hundreds of millions of people worldwide and remain a serious threat to global health. The current SARS-CoV-2 pandemic and other recent geographically- confined viral outbreaks (severe acute respiratory syndrome (SARS), Ebola, dengue, zika and ever-recurring seasonal influenza), also with devastating tolls at sanitary and socio-economic levels, are sobering reminders in this respect. Among the respective pathogenic agents, Zika virus (ZIKV), transmitted by Aedes mosquito vectors and causing the eponymous fever, is particularly insidious in that infection during pregnancy results in complications such as foetal loss, preterm birth or irreversible brain abnormalities, including microcephaly. So far, there is no effective remedy for ZIKV infection, mainly due to the limited ability of antiviral drugs to cross blood-placental and/or blood-brain barriers (BPB and BBB, respectively). Despite its restricted permeability, the BBB is penetrable by a variety of molecules, mainly peptide-based, and named BBB peptide shuttles (BBBpS), able to ferry various payloads (e.g., drugs, antibodies, etc.) into the brain. Recently, we have described peptide-porphyrin conjugates (PPCs) as successful BBBpS-associated drug leads for HIV, an enveloped virus in which group ZIKV also belongs. Herein, we report on several brain-directed, low-toxicity PPCs capable of targeting ZIKV. One of the conjugates, PP-P1, crossing both BPB and BBB, has shown to be effective against ZIKV (IC50 1.08 µM) and has high serum stability (t1/2 ca. 22 h) without altering cell viability at all tested concentrations. Peptide-porphyrin conjugation stands out as a promising strategy to fill the ZIKV treatment gap.

16.
PLoS Negl Trop Dis ; 16(4): e0010359, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35442976

ABSTRACT

A Zika virus (ZIKV) infection during pregnancy can result in severe birth defects such as microcephaly. To date, it is incompletely understood how ZIKV can cross the human placenta. Furthermore, results from studies in pregnant mice and non-human primates are conflicting regarding the role of cross-reactive dengue virus (DENV) antibodies on transplacental ZIKV transmission. Elucidating how ZIKV can cross the placenta and which risk factors contribute to this is important for risk assessment and for potential intervention strategies for transplacental ZIKV transmission. In this study we use an ex vivo human placental perfusion model to study transplacental ZIKV transmission and the effect that cross-reactive DENV antibodies have on this transmission. By using this model, we demonstrate that DENV antibodies significantly increase ZIKV uptake in perfused human placentas and that this increased uptake is neonatal Fc-receptor-dependent. Furthermore, we show that cross-reactive DENV antibodies enhance ZIKV infection in term human placental explants and in primary fetal macrophages but not in primary trophoblasts. Our data supports the hypothesis that presence of cross-reactive DENV antibodies could be an important risk factor for transplacental ZIKV transmission. Furthermore, we demonstrate that the ex vivo placental perfusion model is a relevant and animal friendly model to study transplacental pathogen transmission.


Subject(s)
Dengue Virus , Dengue , Zika Virus Infection , Zika Virus , Animals , Antibodies, Viral , Cross Reactions , Disease Models, Animal , Female , Humans , Mice , Placenta , Pregnancy
17.
Cien Saude Colet ; 27(3): 861-870, 2022 Mar.
Article in Portuguese | MEDLINE | ID: mdl-35293464

ABSTRACT

The Zika epidemic brought to the fore the birth of children with unknown and unexpected needs that demand longitudinal follow-up, strengthening the bond, comprehensiveness and coordination of care in health, which are essential attributes of primary health care (PHC). This article aims to evaluate the orientation of PHC care, using the PCATool-Brasil. The data were collected between 2016 and 2019, by means of interviews with parents of children who were born in a public maternity hospital in Recife (state of Pernambuco) between October 2015 and February 2016, a critical period of the microcephaly outbreak, especially in the Northeast of Brazil. The parents of 109 children participated in the survey, 15.6% of which had a confirmed microcephaly diagnosis. The degree of affiliation and access was sufficient, but the aspects of coordination of care, longitudinality, comprehensiveness, family and community orientation were insufficient. In the context of congenital Zika syndrome, these attributes are essential for the care of children and families. The fostering of health from these domains depends on the orientation of the models of care and their management with state and federal investments. The defense of life depends on the ability to place life above all other rationalities.


A epidemia zika trouxe ao cenário o nascimento de crianças com necessidades desconhecidas e inesperadas que exigem acompanhamento longitudinal, fortalecimento do vínculo, integralidade e coordenação do cuidado, atributos essenciais da atenção primária em saúde (APS). Este artigo tem o objetivo de avaliar a orientação da APS utilizando o instrumento PCATool-Brasil. Os dados foram coletados entre 2016 e 2019 por meio de entrevistas com responsáveis de crianças que nasceram em uma maternidade pública do Recife-PE no período crítico do surto de microcefalia, sobretudo no Nordeste do Brasil. Participaram do inquérito 109 responsáveis, dos quais 15,6% tiveram diagnóstico confirmado de microcefalia para suas crianças. Evidenciou-se a suficiência do grau de afiliação e acesso, mas a insuficiência da coordenação de cuidado, longitudinalidade, integralidade, orientação familiar e comunitária. No contexto da síndrome congênita da zika, esses atributos são imprescindíveis para o cuidado integral de crianças e famílias. A produção de saúde a partir desses domínios depende da orientação dos modelos de atenção e gestão com fortes investimentos estaduais e federal. A defesa da vida depende da capacidade de colocar a vida acima de todas as outras racionalidades.


Subject(s)
Microcephaly , Zika Virus Infection , Zika Virus , Brazil/epidemiology , Child , Female , Humans , Microcephaly/epidemiology , Microcephaly/therapy , Pregnancy , Primary Health Care , Zika Virus Infection/congenital , Zika Virus Infection/epidemiology , Zika Virus Infection/therapy
18.
Cien Saude Colet ; 27(3): 881-894, 2022 Mar.
Article in Portuguese, English | MEDLINE | ID: mdl-35293466

ABSTRACT

In 2015 the correlation between increasing numbers of cases of microcephaly and a zika virus outbreak led to recognition of an epidemic of congenital zika virus syndrome (CZVS), highlighting well-known weaknesses in health care measures. This article examines the network of virtual information available on health service provision for children suffering from CZVS in Rio de Janeiro. Using social media analysis, data on information about services and care institutions were collected from virtual sources using the Google search engine, so as to assess relations among these actors in 2018. The results revealed a fragmented network centred on virtual sources and secondary and tertiary public care services, with striking proximity of press sources to public services. Also salient was the isolation of private services and the lack of dialogue between philanthropic and public services. Moreover, the information offered was found to be insufficient and superficial, despite the gaps in the formal rehabilitation network. The evidence thus suggested the importance of a well-established health care service network and the necessity of fostering communication through virtual media.


A correlação do aumento na incidência de casos de microcefalia em 2015, simultaneamente ao surto do zika vírus, levou ao reconhecimento de uma epidemia pela síndrome congênita pelo vírus zika (SCVZ), que ressaltou as já conhecidas fragilidades nas ações do cuidado em saúde. O objetivo do artigo é analisar a rede virtual de informações sobre a oferta de serviços de saúde para crianças com SCVZ no Rio de Janeiro. A partir da análise de redes sociais, foram coletados dados de fontes virtuais sobre informações de serviços e instituições de atendimento, utilizando o buscador Google, a fim de avaliar as relações entre esses atores em 2018. Os resultados apresentaram uma rede fragmentada, com centralização em fontes virtuais e serviços públicos da atenção secundária e terciária, destacando-se a proximidade das fontes de imprensa com os serviços públicos. Destacou-se também o isolamento dos serviços privados e a não interlocução entre os serviços filantrópicos e os serviços públicos. Além disso, as informações oferecidas mostraram-se insuficientes e superficiais, apesar da lacuna da rede formal de reabilitação. Consequentemente, as evidências apontam para a importância de uma rede bem estabelecida de serviços, bem como a necessidade de fomentar a comunicação por meio de mídias virtuais.


Subject(s)
Microcephaly , Zika Virus Infection , Zika Virus , Brazil/epidemiology , Child , Humans , Microcephaly/epidemiology , Social Network Analysis , Zika Virus Infection/complications , Zika Virus Infection/epidemiology , Zika Virus Infection/therapy
19.
Pathogens ; 11(3)2022 Feb 25.
Article in English | MEDLINE | ID: mdl-35335618

ABSTRACT

The Zika virus (ZIKV) was first isolated from a rhesus macaque in the Zika forest of Uganda in 1947. Isolated cases were reported until 2007, when the first major outbreaks of Zika infection were reported from the Island of Yap in Micronesia and from French Polynesia in 2013. In 2015, ZIKV started to circulate in Latin America, and in 2016, ZIKV was considered by WHO to be a Public Health Emergency of International Concern due to cases of Congenital Zika Syndrome (CZS), a ZIKV-associated complication never observed before. After a peak of cases in 2016, the infection incidence dropped dramatically but still causes concern because of the associated microcephaly cases, especially in regions where the dengue virus (DENV) is endemic and co-circulates with ZIKV. A vaccine could be an important tool to mitigate CZS in endemic countries. However, the immunological relationship between ZIKV and other flaviviruses, especially DENV, and the low numbers of ZIKV infections are potential challenges for developing and testing a vaccine against ZIKV. Here, we discuss ZIKV vaccine development with the perspective of the immunological concerns implicated by DENV-ZIKV cross-reactivity and the use of a controlled human infection model (CHIM) as a tool to accelerate vaccine development.

20.
Front Microbiol ; 13: 743147, 2022.
Article in English | MEDLINE | ID: mdl-35308394

ABSTRACT

Zika virus (ZIKV) is a mosquito-borne, single-stranded RNA virus belonging to the genus Flavivirus. Although ZIKV infection is usually known to exhibit mild clinical symptoms, intrauterine ZIKV infections have been associated with severe neurological manifestations, including microcephaly and Guillain Barre syndrome (GBS). Therefore, it is imperative to understand the mechanisms of ZIKV entry into the central nervous system (CNS) and its effect on brain cells. Several routes of neuro-invasion have been identified, among which blood-brain barrier (BBB) disruption is the commonest mode of access. The molecular receptors involved in viral entry remain unknown; with various proposed molecular ZIKV-host interactions including potential non-receptor mediated cellular entry. As ZIKV invade neuronal cells, they trigger neurotoxic mechanisms via cell-autonomous and non-cell autonomous pathways, resulting in neurogenesis dysfunction, viral replication, and cell death, all of which eventually lead to microcephaly. Together, our understanding of the biological mechanisms of ZIKV exposure would aid in the development of anti-ZIKV therapies targeting host cellular and/or viral components to combat ZIKV infection and its neurological manifestations. In this present work, we review the current understanding of ZIKV entry mechanisms into the CNS and its implications on the brain. We also highlight the status of the drug repurposing approach for the development of potential antiviral drugs against ZIKV.

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