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1.
Biomedicines ; 9(12)2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34944678

RESUMO

Although dengue virus (DENV) affects almost half of the world's population there are neither preventive treatments nor any long-lasting and protective vaccines available at this time. The complexity of the protective immune response to DENV is still not fully understood. The most advanced vaccine candidates focus specifically on humoral immune responses and the production of virus-neutralizing antibodies. However, results from several recent studies have revealed the protective role of T cells in the immune response to DENV. Hence, in this study, we generated a novel and potent DENV vaccine candidate based on an Orf virus (ORFV, genus Parapoxvirus) vector platform engineered to encode five highly conserved or cross-reactive DENV human leukocyte antigen (HLA)-A*02- or HLA-B*07-restricted epitopes as minigenes (ORFV-DENV). We showed that ORFV-DENV facilitates the in vitro priming of CD8+ T cells from healthy blood donors based on responses to each of the encoded immunogenic peptides. Moreover, we demonstrated that peripheral blood mononuclear cells isolated from clinically confirmed DENV-positive donors stimulated with ORFV-DENV generate cytotoxic T cell responses to at least three of the expressed DENV peptides. Finally, we showed that ORFV-DENV could activate CD8+ T cells isolated from donors who had recovered from Zika virus (ZIKV) infection. ZIKV belongs to the same virus family (Flaviviridae) and has epitope sequences that are homologous to those of DENV. We found that highly conserved HLA-B*07-restricted ZIKV and DENV epitopes induced functional CD8+ T cell responses in PBMCs isolated from confirmed ZIKV-positive donors. In summary, this proof-of-concept study characterizes a promising new ORFV D1701-VrV-based DENV vaccine candidate that induces broad and functional epitope-specific CD8+ T cell responses.

2.
Am J Trop Med Hyg ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34814106

RESUMO

In 2017, a major outbreak of Zika virus (ZIKV) infection took place in Chincha Province, Peru, where arboviral circulation had never been reported before. We conducted a cross-sectional survey (March-May 2019) in two districts of Chincha Province: Pueblo Nuevo and Chincha Baja. We included residents who were 20 to 40 years old and who had lived in these districts for at least 1 year. Serological testing combined screening with a commercial NS1 protein-based Zika IgG ELISA, and confirmation by a cytopathic effect-based virus neutralization test (VNT). Prevalence ratios (PRs) were calculated using Poisson regression with robust error variance. Four hundred participants, divided equally among districts, were enrolled. Anti-ZIKV IgG ELISA was positive for 42 participants (10.5%) and borderline for 12 (3%). Fifty-two of these 54 samples were confirmed positive by ZIKV VNT (13% of the total population). The Pueblo Nuevo district exhibited a greater ZIKV seroprevalence based on VNT results than the Chincha Baja district (23.5% versus 2.5%), with participants from the Pueblo Nuevo district being 9.4 times more likely to have a positive ZIKV VNT result. Average monthly income greater than the minimum wage and adequate water storage were found to be protective factors (PR, 0.29 and 0.24, respectively). In multivariate analysis, living in the Pueblo Nuevo district and a personal history of fever and rash were strong predictors of ZIKV positivity by VNT. The low ZIKV seroprevalence should prompt health authorities to stimulate interventions to prevent potential future outbreaks. In the Pueblo Nuevo district, the seroprevalence was greater but presumably not sufficient to ensure protective herd immunity.

3.
RSC Med Chem ; 12(9): 1525-1539, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34671736

RESUMO

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.

4.
Malar J ; 20(1): 416, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34688294

RESUMO

BACKGROUND: Although the association between malaria and anaemia is widely studied in patient cohorts, the population-representative causal effects of malaria on anaemia remain unknown. This study estimated the malaria-induced decrease in haemoglobin levels among young children in malaria-endemic Burkina Faso. METHODS: The study was based on pooled individual-level nationally representative health survey data (2010-2011, 2014, 2017-2018) from 17 599 children under 5 years of age. This data was used to estimate the effects of malaria on haemoglobin concentration, controlling for household fixed-effects, age, and sex in a series of regression analyses. The fixed-effects controlled for observed and unobserved confounding on the household level and allowed to determine the impact of malaria infection status on haemoglobin levels and anaemia prevalence. Furthermore, the diagnostic results from microscopy and rapid diagnostic tests were leveraged to provide a quasi-longitudinal perspective of acute and prolonged effects after malaria infection. RESULTS: The prevalence of both malaria (survey prevalence ranging from 17.4% to 65.2%) and anaemia (survey prevalence ranging from 74% to 88.2%) was very high in the included surveys. Malaria was estimated to significantly reduce haemoglobin levels, with an overall effect of - 7.5 g/dL (95% CI - 8.5, - 6.5). Acute malaria resulted in a - 7.7 g/dL (95% CI - 8.8, - 6.6) decrease in haemoglobin levels. Recent malaria without current parasitaemia decreased haemoglobin concentration by - 7.1 g/dL (95% CI - 8.3, - 5.9). The in-sample predicted prevalence of severe anaemia was 9.4% among malaria positives, but only 2.2% among children without malaria. CONCLUSION: Malaria infection has a strong detrimental effect on haemoglobin levels among young children in Burkina Faso. This effect seems to carry over even after acute infection, indicating prolonged haemoglobin reductions even after successful parasite-elimination. The quasi-experimental fixed-effect approach adds a population level perspective to existing clinical evidence.


Assuntos
Anemia/epidemiologia , Hemoglobinas/metabolismo , Malária/epidemiologia , Parasitemia/epidemiologia , Anemia/parasitologia , Burkina Faso/epidemiologia , Pré-Escolar , Características da Família , Feminino , Humanos , Lactente , Recém-Nascido , Malária/parasitologia , Masculino , Parasitemia/parasitologia , Prevalência , Fatores de Risco
5.
PLoS One ; 16(8): e0256426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34437595

RESUMO

OBJECTIVE: We undertook a systematic review of the literature to explore the prevalence of post-traumatic stress disorder (PTSD) in Palestinian children and adolescents exposed to political violence. This is the first systematic review and meta-analysis of the prevalence of PTSD in this population. METHODS: PubMed, Embase, PsycInfo, Google Scholar and Cochrane library were searched until June 2020. To estimate the prevalence of PTSD, sub-group and meta-analysis were conducted. RESULTS: The search resulted in 2786 studies, of which 28 articles representing 32 samples with a total of 15,121 participants from Gaza Strip and West Bank met either the DSM-4 or DSM-5 criteria and were included. The pooled prevalence of PTSD was 36% (95% CI 30-41%; I2 98.6%) and ranged from 6% to 70%. Sub-group analysis showed that the PTSD prevalence did not differ according to region (West Bank, Gaza Strip) and tended to decrease after including only studies using a representative sample (p<0.001), and among those with low risk of bias (p<0.001). Visual inspection of the included studies revealed significant discrepancies in study design and assessment measures. CONCLUSION: We identified high prevalence of PTSD among Palestinian children and adolescents exposed to political violence. However, the pooled results should be interpreted with caution, due to the high heterogeneity and risk of bias in the included studies. These limitations also reflect the challenge in conceptualizing and measuring PTSD in the Palestinian context with a background of continuous and cumulative trauma. Understanding the contextual factors and developing locally adapted survey measures are of relevance to future research, public health planning, and the provision of mental healthcare in Palestine.

6.
Res Synth Methods ; 12(6): 796-815, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34312994

RESUMO

Ideally, a meta-analysis will summarize data from several unbiased studies. Here we look into the less than ideal situation in which contributing studies may be compromised by non-differential measurement error in the exposure variable. Specifically, we consider a meta-analysis for the association between a continuous outcome variable and one or more continuous exposure variables, where the associations may be quantified as regression coefficients of a linear regression model. A flexible Bayesian framework is developed which allows one to obtain appropriate point and interval estimates with varying degrees of prior knowledge about the magnitude of the measurement error. We also demonstrate how, if individual-participant data (IPD) are available, the Bayesian meta-analysis model can adjust for multiple participant-level covariates, these being measured with or without measurement error.


Assuntos
Teorema de Bayes , Humanos , Modelos Lineares
7.
Elife ; 102021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34154705

RESUMO

Background: Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD). Methods: We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included. Results: On days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults. Conclusions: Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients. Funding: This study was supported by the EU's Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation.


Assuntos
Dengue/sangue , Dengue/metabolismo , Inflamação/metabolismo , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Citocinas/sangue , Citocinas/metabolismo , Dengue/patologia , Feminino , Humanos , Masculino , Adulto Jovem
8.
Prenat Diagn ; 41(8): 998-1008, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34101871

RESUMO

OBJECTIVE: Identify the potential for and risk factors of SARS-CoV-2 vertical transmission. METHODS: Symptomatic pregnant women with COVID-19 diagnosis in whom PCR for SARS-CoV-2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS-CoV-2 positivity in AF and/or CB on neonatal outcomes were investigated. RESULTS: Overall 73.4% (80/109) were admitted in hospital due to COVID-19, 22.9% needed intensive care and there were four maternal deaths. Positive RT-PCR for SARS-CoV-2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID-19 symptoms and delivery was inversely associated with SARS-CoV-2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS-CoV-2 in AF and/or CB (p = 0.001). SARS-CoV-2 positivity in the compartments was not associated with neonatal outcomes. CONCLUSION: Vertical transmission is possible in pregnant women with COVID-19 and a shorter interval between maternal symptoms and delivery is an influencing factor.


Assuntos
COVID-19/transmissão , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/isolamento & purificação , Adulto , Líquido Amniótico/virologia , Brasil/epidemiologia , COVID-19/mortalidade , COVID-19/virologia , Colostro/virologia , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/mortalidade , Estudos Prospectivos , Adulto Jovem
9.
J Clin Microbiol ; 59(6)2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33795412

RESUMO

Serological testing of large representative populations for antibodies to SARS-CoV-2 is needed to estimate seroprevalence, transmission dynamics, and the duration of antibody responses from natural infection and vaccination. In this study, a high-throughput SARS-CoV-2 multiplex microsphere immunoassay (MMIA) was developed for the receptor binding domain (RBD) and nucleocapsid (N) that was more sensitive than enzyme-linked immunosorbent assay (ELISA) (98% versus 87%). The MMIA was then applied and validated in 264 first responders in Colorado using serum and dried blood spot (DBS) eluates, compared to ELISA, and evaluated for neutralizing antibodies. Four percent (11/264) of first responders were seropositive in July to August 2020. Serum and DBS were highly correlated for anti-RBD and anti-N antibodies (R = 0.83, P < 0.0001 and R = 0.87, P < 0.0001, respectively) by MMIA. The MMIA accurately predicted SARS-CoV-2 neutralizing antibodies using DBS (R = 0.76, P = 0.037). On repeat antibody testing 3 months later, anti-RBD IgG decreased less rapidly than anti-N IgG measured by MMIA, with a median change in geometric median fluorescence intensity of 62% versus 79% (P < 0.01) for anti-RBD and anti-N IgG, respectively. This novel MMIA using DBS could be scalable for rapid and affordable SARS-CoV-2 serosurveillance in the United States and globally.


Assuntos
COVID-19 , Socorristas , Anticorpos Antivirais , Teste Sorológico para COVID-19 , Colorado , Humanos , Imunoensaio , Microesferas , SARS-CoV-2 , Estudos Soroepidemiológicos
10.
PLoS Negl Trop Dis ; 15(4): e0009336, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33872309

RESUMO

BACKGROUND: Serological diagnosis of Zika virus (ZIKV) infection is challenging because of the antibody cross-reactivity among flaviviruses. At the same time, the role of Nucleic Acid Testing (NAT) is limited by the low proportion of symptomatic infections and the low average viral load. Here, we compared the diagnostic performance of commercially available IgM, IgAM, and IgG ELISAs in sequential samples during the ZIKV and chikungunya (CHIKV) epidemics and co-circulation of dengue virus (DENV) in Brazil and Venezuela. METHODOLOGY/PRINCIPAL FINDINGS: Acute (day of illness 1-5) and follow-up (day of illness ≥ 6) blood samples were collected from nine hundred and seven symptomatic patients enrolled in a prospective multicenter study between June 2012 and August 2016. Acute samples were tested by RT-PCR for ZIKV, DENV, and CHIKV. Acute and follow-up samples were tested for IgM, IgAM, and IgG antibodies to ZIKV using commercially available ELISAs. Among follow-up samples with a RT-PCR confirmed ZIKV infection, anti-ZIKV IgAM sensitivity was 93.5% (43/46), while IgM and IgG exhibited sensitivities of 30.3% (10/33) and 72% (18/25), respectively. An additional 24% (26/109) of ZIKV infections were detected via IgAM seroconversion in ZIKV/DENV/CHIKV RT-PCR negative patients. The specificity of anti-ZIKV IgM was estimated at 93% and that of IgAM at 85%. CONCLUSIONS/SIGNIFICANCE: Our findings exemplify the challenges of the assessment of test performance for ZIKV serological tests in the real-world setting, during co-circulation of DENV, ZIKV, and CHIKV. However, we can also demonstrate that the IgAM immunoassay exhibits superior sensitivity to detect ZIKV RT-PCR confirmed infections compared to IgG and IgM immunoassays. The IgAM assay also proves to be promising for detection of anti-ZIKV seroconversions in sequential samples, both in ZIKV PCR-positive as well as PCR-negative patients, making this a candidate assay for serological monitoring of pregnant women in future ZIKV outbreaks.


Assuntos
Febre de Chikungunya/diagnóstico , Dengue/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Testes Sorológicos/métodos , Infecção por Zika virus/diagnóstico , Adolescente , Adulto , Anticorpos Antivirais/sangue , Sangue/virologia , Brasil , Criança , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Estudos Prospectivos , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , Venezuela , Adulto Jovem
11.
PLoS One ; 16(4): e0250778, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33914795

RESUMO

INTRODUCTION: Pooling (or combining) and analysing observational, longitudinal data at the individual level facilitates inference through increased sample sizes, allowing for joint estimation of study- and individual-level exposure variables, and better enabling the assessment of rare exposures and diseases. Empirical studies leveraging such methods when randomization is unethical or impractical have grown in the health sciences in recent years. The adoption of so-called "causal" methods to account for both/either measured and/or unmeasured confounders is an important addition to the methodological toolkit for understanding the distribution, progression, and consequences of infectious diseases (IDs) and interventions on IDs. In the face of the Covid-19 pandemic and in the absence of systematic randomization of exposures or interventions, the value of these methods is even more apparent. Yet to our knowledge, no studies have assessed how causal methods involving pooling individual-level, observational, longitudinal data are being applied in ID-related research. In this systematic review, we assess how these methods are used and reported in ID-related research over the last 10 years. Findings will facilitate evaluation of trends of causal methods for ID research and lead to concrete recommendations for how to apply these methods where gaps in methodological rigor are identified. METHODS AND ANALYSIS: We will apply MeSH and text terms to identify relevant studies from EBSCO (Academic Search Complete, Business Source Premier, CINAHL, EconLit with Full Text, PsychINFO), EMBASE, PubMed, and Web of Science. Eligible studies are those that apply causal methods to account for confounding when assessing the effects of an intervention or exposure on an ID-related outcome using pooled, individual-level data from 2 or more longitudinal, observational studies. Titles, abstracts, and full-text articles, will be independently screened by two reviewers using Covidence software. Discrepancies will be resolved by a third reviewer. This systematic review protocol has been registered with PROSPERO (CRD42020204104).


Assuntos
Doenças Transmissíveis/epidemiologia , COVID-19/epidemiologia , Causalidade , Humanos , Estudos Longitudinais , Metanálise como Assunto , Revisões Sistemáticas como Assunto
13.
J Infect Dis ; 224(6): 1060-1068, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-33528564

RESUMO

BACKGROUND: Zika virus (ZIKV) is associated with severe congenital abnormalities and laboratory diagnosis of antenatal infection is difficult. Here we evaluated ZIKV neutralizing antibody (nAb) kinetics in infants born to mothers with PCR-confirmed ZIKV infection during pregnancy. METHODS: Neonates (n = 98) had serum specimens tested repeatedly for ZIKV nAb over the first 2 years of life using virus neutralization test (VNT). ZIKV neonatal infection was confirmed by RT-PCR in blood or urine and/or presence of ZIKV IgM antibodies, and results were correlated with infant clinical features. RESULTS: Postnatal laboratory evidence of ZIKV vertical transmission was obtained for 60.2% of children, while 32.7% exhibited clinical abnormalities. Congenital abnormalities were found in 37.3% of children with confirmed ZIKV infection and 31.0% of children without confirmed infection (P = .734). All but 1 child displayed a physiologic decline in ZIKV nAb, reflecting maternal antibody decay, despite an early ZIKV-IgM response in one-third of infants. CONCLUSIONS: Infants with antenatal ZIKV exposure do not develop ZIKV nAb despite an early IgM response. Therefore, ZIKV VNT in children is not useful for diagnosis of congenital infection. In light of these findings, it remains to be determined if children infected in utero are potentially susceptible to reinfection.

14.
PLoS Negl Trop Dis ; 15(1): e0008984, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395432

RESUMO

Zika virus (ZIKV) emerged in Brazil during 2013-2014 causing an epidemic of previously unknown congenital abnormalities. The frequency of severe congenital abnormalities after maternal ZIKV infection revealed an unexplained geographic variability, especially between the Northeast and the rest of Brazil. Several reasons for this variability have been discussed. Prior immunity against Dengue virus (DENV) affecting ZIKV seems to be the most likely explanation. Here we summarise the current evidence regarding this prominent co-factor to potentially explain the geographic variability. This systematic review followed the PRISMA guidelines. The search was conducted up to May 15th, 2020, focussing on immunological interactions from Zika virus with previous Dengue virus infections as potential teratogenic effect for the foetus. Eight out of 339 screened studies reported on the association between ZIKV, prior DENV infection and microcephaly, mostly focusing on antibody-dependent enhancement (ADE) as potential pathomechanism. Prior DENV infection was associated with enhancement for ZIKV infection and increased neurovirulence in one included in vitro study only. Interestingly, the seven in vivo studies exhibited a heterogeneous picture with three studies showing a protective effect of prior DENV infections and others no effect at all. According to several studies, socio-economic factors are associated with increased risk for microcephaly. Very few studies addressed the question of unexplained variability of infection-related microcephaly. Many studies focussed on ADE as mechanism without measuring microcephaly as endpoint. Interestingly, three of the included studies reported a protective effect of prior DENV infection against microcephaly. This systematic review strengthens the hypothesis that immune priming after recent DENV infection is the crucial factor for determining protection or enhancement activity. It is of high importance that the currently ongoing prospective studies include a harmonised assessment of the potential candidate co-factors.


Assuntos
Anormalidades Congênitas/etiologia , Dengue/complicações , Complicações Infecciosas na Gravidez , Infecção por Zika virus/complicações , Dengue/imunologia , Feminino , Humanos , Microcefalia/etiologia , Gravidez , Infecção por Zika virus/imunologia
15.
Viruses ; 13(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430059

RESUMO

BACKGROUND: Zika virus (ZIKV) infection during pregnancy usually shows only mild symptoms and is frequently subclinical. However, it can be vertically transmitted to the fetus, causing microcephaly and other congenital defects. During pregnancy, the immune environment modifications can alter the response to viruses in general and ZIKV in particular. OBJECTIVE: To describe the role of pregnancy in the systemic pro- and anti-inflammatory response during symptomatic ZIKV infection. MATERIALS AND METHODS: A multiplex assay was used to measure 25 cytokines, chemokines, and receptors in 110 serum samples from pregnant and nonpregnant women with and without ZIKV infection with and without symptoms. Samples were collected through an epidemiological surveillance system. RESULTS: Samples from pregnant women with ZIKV infection showed a higher viral load but had similar profiles of inflammatory markers as compared with nonpregnant infected women, except for CXCL10 that was higher in infected pregnant women. Notably, the presence of ZIKV in pregnancy favored a regulatory profile by significantly increasing anti-inflammatory cytokines such as interleukin (IL)-10, receptors IL-1RA, and IL-2R, but only those pro-inflammatory cytokines such as IL-6, interferon (IFN)-α, IFN-γ and IL-17 that are essential for the antiviral response. Interestingly, there were no differences between symptomatic and weakly symptomatic ZIKV-infected groups. CONCLUSION: Our results revealed a systemic anti-inflammatory cytokine and chemokine profile that could participate in the control of the virus. The anti-inflammatory response in pregnant women infected with ZIKA was characterized by high CXCL10, a cytokine that has been correlated with congenital malformations.


Assuntos
Quimiocina CXCL10/metabolismo , Citocinas/metabolismo , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/virologia , Carga Viral , Infecção por Zika virus/metabolismo , Infecção por Zika virus/virologia , Zika virus/fisiologia , Adulto , Biomarcadores , Feminino , Humanos , Imunomodulação , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Trimestres da Gravidez , Adulto Jovem , Infecção por Zika virus/imunologia
17.
J Occup Environ Med ; 63(3): 191-198, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33298759

RESUMO

OBJECTIVES: Define the seroprevalence and risk factors for SARS-CoV-2 antibodies in Arapahoe County, Colorado first responders (eg, law enforcement, human services, fire departments). METHODS: Two hundred sixty four first responders were enrolled June to July 2020. SARS-CoV-2 seropositivity was defined as detection of immunoglobulin G (IgG) antibodies to both spike receptor binding domain and nucleocapsid in venous blood by validated enzyme-linked immunosorbent assay. We compared risk factors for being seropositive versus seronegative. RESULTS: 4% (11/264) were SARS-CoV-2 seropositive. Seropositive participants were significantly more likely to have lung disease (% seropositive, % seronegative; P-value) (36%, 8%; P = 0.01), prior SARS-CoV-2/COVID-19 testing (36%, 8%; P ≤ 0.01), a prior positive result (18%, less than 1%), and to believe they previously had COVID-19 (64%, 15%; P < 0.01). Only 15% of those believing they had COVID-19 had anti-SARS-CoV-2 antibodies. CONCLUSIONS: Human services employees and individuals with lung disease are at SARS-CoV-2 exposure risk. Few individuals believed they had COVID-19 had prior exposure.


Assuntos
COVID-19/epidemiologia , Socorristas/estatística & dados numéricos , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/sangue , COVID-19/diagnóstico , COVID-19/patologia , COVID-19/transmissão , Teste Sorológico para COVID-19 , Colorado/epidemiologia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Estudos Soroepidemiológicos
18.
Clin Infect Dis ; 72(12): e1074-e1083, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33340040

RESUMO

BACKGROUND: One of the generally accepted constructs of dengue pathogenesis is that clinical disease severity is at least partially dependent upon plasma viremia, yet data on plasma viremia in primary versus secondary infections and in relation to clinically relevant endpoints remain limited and contradictory. METHODS: Using a large database comprising detailed clinical and laboratory characterization of Vietnamese participants enrolled in a series of research studies executed over a 15-year period, we explored relationships between plasma viremia measured by reverse transcription-polymerase chain reaction and 3 clinically relevant endpoints-severe dengue, plasma leakage, and hospitalization-in the dengue-confirmed cases. All 4 dengue serotypes and both primary and secondary infections were well represented. In our logistic regression models we allowed for a nonlinear effect of viremia and for associations between viremia and outcome to differ by age, serotype, host immune status, and illness day at study enrollment. RESULTS: Among 5642 dengue-confirmed cases we identified 259 (4.6%) severe dengue cases, 701 (12.4%) patients with plasma leakage, and 1441 of 4008 (40.0%) patients recruited in outpatient settings who were subsequently hospitalized. From the early febrile phase onwards, higher viremia increased the risk of developing all 3 endpoints, but effect sizes were modest (ORs ranging from 1.12-1.27 per 1-log increase) compared with the effects of a secondary immune response (ORs, 1.67-7.76). The associations were consistent across age, serotype, and immune status groups, and in the various sensitivity and subgroup analyses we undertook. CONCLUSIONS: Higher plasma viremia is associated with increased dengue severity, regardless of serotype or immune status.


Assuntos
Vírus da Dengue , Dengue , Dengue/epidemiologia , Humanos , Sorogrupo , Viremia
19.
J Infect Dis ; 223(4): 673-685, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32888023

RESUMO

BACKGROUND: Zika virus (ZIKV) is a mosquito-borne virus that is also transmitted sexually; however, the epidemiological relevance of ZIKV sexual transmission in endemic regions is unclear. METHODS: We performed a household-based serosurvey in Northeast Brazil to evaluate the differential exposure to ZIKV and chikungunya virus (CHIKV) among households. Individuals who participated in our previous arboviral disease cohort (indexes) were recontacted and enrolled, and their household members were newly enrolled. RESULTS: The relative risk of sexual partners being ZIKV-seropositive when living with a ZIKV-seropositive index participant was significantly higher, whereas this was not observed among nonsexual partners of the index. For CHIKV, both sexual and nonsexual partner household members living with a CHIKV-seropositive index had a significantly higher risk of being seropositive. In the nonindex-based dyadic and generalized linear mixed model analyses, the odds of sexual dyads having a concordant ZIKV plaque reduction neutralization test result was significantly higher. We have also analyzed retrospective clinical data according to the participants' exposure to ZIKV and CHIKV. CONCLUSIONS: Our data suggest that ZIKV sexual transmission may be a key factor for the high ZIKV seroprevalence among households in endemic areas and raises important questions about differential disease from the 2 modes of transmission.


Assuntos
Parceiros Sexuais , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/transmissão , Vírus Chikungunya/imunologia , Criança , Pré-Escolar , Características da Família , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Estudos Soroepidemiológicos , Comportamento Sexual , Doenças Virais Sexualmente Transmissíveis/transmissão , Adulto Jovem , Zika virus/imunologia
20.
BMJ Open ; 10(12): e035307, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33323426

RESUMO

INTRODUCTION: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean. METHODS AND ANALYSIS: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach. ETHICS AND DISSEMINATION: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities.


Assuntos
Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Região do Caribe/epidemiologia , Estudos de Coortes , Feminino , Humanos , América Latina/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Prospectivos , Risco , Infecção por Zika virus/epidemiologia
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