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Aim: To evaluate the clinical characteristics, diagnostic approach, and treatment outcomes of tuberculosis (TB) in children living in a high-burden metropolitan area. Methods: This was a retrospective study, based on a medical chart review, involving children under 15 years old treated for TB between 2007 and 2016, in four primary health units (PHU) and three reference centers (RC) in five cities of Rio de Janeiro metropolitan area. Factors associated with TB treatment setting, microbiological diagnosis, and treatment outcomes were evaluated. Results: A total of 544 children were enrolled; 71% were treated in PHU, 36% were under 5 years old, and 72% had pulmonary TB (PTB). The HIV prevalence was 10% (31/322). Fifty-three percent had at least one microbiological test for TB, 68% of them (196/287) had TB confirmed. Among 222 children with previous TB contact, information on LTBI was available for 78 (35%), and only 17% (13/78) were treated. Extrapulmonary TB (56% vs 32%), microbiologically confirmed TB (77% vs 60%), and HIV positivity (18.5% vs 4.0%) were significantly more frequent in RC. Treatment in RC (odds ratio (OR) 3.08, 95% confidence interval (CI) 1.74–5.44) and PTB (OR 2.47, 95% CI 1.34–4.56) were independently associated with a microbiological diagnosis of TB. The treatment success rate was 85%. In the logistic regression analysis, HIV-infected children had a 2.5-fold higher risk of an unfavorable outcome (OR 2.53, 95% CI 1.0–6.38; p = 0.05). Conclusions: Opportunities for TB prevention and early TB treatment are missed due to suboptimal close contact screening. Microbiological diagnosis of TB and drug susceptibility testing in children should be made available through more sensitive and accessible tests.

ABSTRACT This study investigated the potential use of the String Test (ST) for the diagnosis of pulmonary tuberculosis (PTB) in children and adolescents. This is a case series of patients aged 4-15 years presenting with clinically presumed PTB and submitted to ST in three pediatric TB referral centers in Brazil, between November 2017 and July 2020. The ST was performed in the morning, after 4-12 h of fasting, followed by ingestion of the capsule by the patient, which was attached to the patient’s malar region. The material was collected for simultaneous smear microscopy (acid-fast bacilli - AFB), culture and the molecular investigation by the GeneXpert MTB/RIF®. Thirty-three patients with presumed PTB were included and ST was performed in 26 (78.8%) of them and 7 (21.2%) patients could not swallow the cord. The diagnosis of PTB was established in 11 (42.3%) of the 26 patients who underwent the ST. The diagnosis of PTB was confirmed (by culture or GeneXpert MTB/RIF®) in 5 patients, 4 of whom were also positive by the ST. Two of them showed positivity by the GeneXpert MTB/RIF® only in the ST sample. Two other patients had a positive ST following the induced sputum test (AFB, GeneXpert MTB/RIF®, and positive culture in both specimens). Thus, ST was positive in 36.4% of the patients in whom PTB was diagnosed. ST could be a useful test for diagnosing PTB in children and adolescents.

Quase 6 milhões de crianças com até 5 anos morreram em 2015 (UNICEF), mais da metade por doenças infecciosas evitáveis pela vacinação. Outras enfermidades ainda não são combatidas por vacinas, como aquelas causadas por arbovírus. A Zika (ZIKV) é em geral uma doença branda, autolimitada, mas, na gravidez, pode levar à um espectro de malformações congênitas aos neonatos. Demonstramos que crianças nascidas de mulheres infectadas por ZIKV na gravidez apresentam baixa detecção de anticorpos neutralizantes (AbNeut) anti-ZIKV. Essas crianças são vacinadas de acordo com o Programa Nacional de Imunização, incluindo as vacinas tríplice viral (TV: Sarampo, Caxumba, Rubéola) e a do vírus Febre amarela (YFV). TV e YFV são vacinas de vírus vivos atenuados, administradas em duas doses até os 4 anos. Neste estudo, propomos avaliar a imunidade dessas crianças aos antígenos vacinais dos vírus sarampo (MeV) e rubéola e, YFV. O estudo consiste na coleta de sangue de 90 crianças de 4-5 anos, dispostas em três grupos: G1, sem alterações clínicas, nascidas de mães com qRT-PCR negativo de ZIKV; G2, assintomáticas nascidas de mães com ZIKV qRT-PCR+ ou com critério clínico-epidemiológico de Zika e; G3, com Síndrome da Zika Congênita nascidas de mães ZIKV qRT-PCR+ ou critério clínico-epidemiológico. A imunogenicidade está sendo avaliada pela dosagem dos anticorpos IgG anti-MeV e anti-rubéola (EuroImmun) e detecção de anticorpos neutralizantes (AbNeut) contra YFV por PRNT50. Até o momento, crianças do G1 (apenas n = 3) tomaram 2,7 ± 1,2 doses da TV há 34±19 meses; G2 (apenas n = 3) tomaram 2,6 ± 0,6 doses da TV há 37 ± 6 meses e, G3 (n = 16) tomaram 2,6 ± 0,8 doses da TV há 32 ± 5 meses. Os títulos de IgG anti-MeV foram de 391±314 UI/mL para G1 (2/3 positivos), 150 ± 106 UI/mL para G2 (todos negativos) e 3428 ± 10463 UI/mL para G3 (10/16 positivos). Os títulos de IgG anti-rubéola foram de 55 ± 38 UI/mL para G1 (todos positivos), 23 ± 18 UI/mL para G2 (2/3 positivos) e 35 ± 43 UI/mL para G3 (13/16 positivos). Para a vacina YFV, as G1 tomaram 1,3 ± 0,6 doses há 34 ± 24 meses; G2 tomaram duas doses há 9 ± 3 meses e G3 tomaram 1,3 ± 0,5 doses há 28 ± 18 meses. Os títulos de PRNT50 foram ≥ 320 para G1, de 160 a ≥ 320 para G2 e de 40 a ≥ 320 para G3. Todas as crianças apresentaram títulos de AbNeut anti-YFV. Parece haver diferença na imunogenicidade à TV em relação aos três grupos e imunogenicidade efetiva a vacina YFV em todas as crianças, que serão confirmados aumentando a disponibilidade das amostras.

Introdução/objetivos: Infecções pelo ZIKV ocasionalmente podem desencadear um amplo espectro de malformações congênitas, coletivamente denominados de Síndrome da Zika Congênita. Um número restrito de estudos descreve a imunidade na infecção pelo ZIKV durante a gravidez, tanto em modelos experimentais, como em pacientes. Desta forma, buscamos determinar se a resposta imunológica de memória específica ao ZIKV, 2 a 3 anos após a infecção primária, desenvolvida por mães infectadas durante a gravidez e de seus filhos expostos ao vírus por via transplacentária é efetiva e duradoura. Métodos: A resposta efetora de linfócitos T de vinte e uma mães e dezoito crianças foi avaliada por ELISPOT de IFN- γ e citometria de fluxo após estimulação com megapools de ZIKV. Resultados: Como principais achados, observamos uma alta frequência de linfócitos T CD4+ de perfil Th2 efetora/memória e de linfócitos T CD8+ de perfil Th1 naive, seguida de linfócitos T CD8+ de perfil Tc2 efetora/memória nas mães e crianças, indicando que essas células estariam, de alguma forma, auxiliando a resposta imune humoral de mães e crianças com histórico de infecção pelo ZIKV. Observamos ainda, que a capacidade de degranulação e produção de IFN-γ pelos linfócitos T CD4+ foram detectadas nos três grupos de pacientes mesmo após 2-3 anos de infecção, indicando que os linfócitos T CD4+ mantém um perfil de memória de longa duração. Por outro lado, as habilidades de degranulação e produção de IFN-γ pelos linfócitos T CD8+ foram ausentes ou baixos nos três grupos de pacientes após o mesmo período, indicando que os linfócitos T CD8+ mantém um perfil de memória de curta duração quando comparado aos T CD4+. Por fim, demonstramos que os linfócitos T CD4+ TEMRA são os principais produtores de IFN-γ. Conclusão: É importante relembrar que embora não estejamos estudando a infecção aguda na gestação, nossos dados refletem um imprint do que provavelmente ocorreu na infecção aguda. Desta forma, nosso estudo descreve pontos importantes de relevância imunológica, clínica e epidemiológica, particularmente em relação aos linfócitos T CD8+ de memória específicos ao ZIKV que são gerados, mas mantidos por um curto período. Também evidenciarmos que as respostas de linfócitos T específicas ao ZIKV nas mães parecem não ter sido diferenciadas na fase aguda e que, portanto, não estariam relacionadas ao desfecho clínico dos bebês.

A infecção pelo ZIKV durante a gestação pode levar ao desenvolvimento de anormalidade congênitas, conhecidas como Síndrome da Zika Congênita (SZC). Níveis elevados de citocinas relacionadas ao perfil Th17, como IL17, IL1β e IL6 foram demonstrados durante a infecção pelo ZIKV. Além disso, sabe-se que, durante a gestação, são detectados níveis elevados de TGFβ, o que poderia criar um ambiente favorável à diferenciação de células TCD4 naive em Th17. Sendo assim, recrutamos uma coorte composta por mulheres infectadas durante a gravidez e crianças expostas ao ZIKV por transmissão vertical e que desenvolveram ou não a SZC. Avaliamos mães infectadas pelo ZIKV durante a gestação (Mães, n = 21) e crianças nascidas (Crianças, n = 17) de mães que relataram rash cutâneo durante a gravidez. Como grupo controle, mulheres infectadas pelo ZIKV, mas fora do período gestacional, foram recrutadas (Mulheres, n = 6). Todos os doadores foram avaliados 2-3 anos após a infecção aguda por ZIKV. O diagnóstico da infecção por ZIKV nas mulheres adultas foi confirmado por qRT-PCR. Por citometria de fluxo, caracterizamos (1) subpopulações de células Th17, utilizando os marcadores CCR6, CXCR3 e CCR4 e o perfil de memória (CD45RA e CCR7); (2) frequência de células TCD4 IL-17A+ e TCD4 IL-17A+IFN-γ+ após estimulação in vitro com peptídeos do ZIKV (ZIKV MP). Além disso, quantificamos as citocinas IL17A, IL6 e TGFβ nos sobrenadantes de cultura após a estimulação in vitro com ZIKV MP por ELISA. Observamos maior frequência de células Th17 em Mães e Crianças e no grupo de Mulheres, as células CCR6+DN foram as mais frequentes. Detectamos níveis basais elevados de IL17A em Mães e Crianças; de IL6 em crianças; e TGFβ nas Mães. Após estimulação com ZIKV MP, foi observada redução na produção de IL17A e TGFβ no grupo de Mães, assim como uma diminuição na frequência de células T CD4 IL17A+ (Th17), especialmente naquelas que deram à luz bebês com SZC. Porém, um aumento nas células T CD4 IL17A+IFNγ+ (Th1Th17) foi detectado neste mesmo grupo e nos dois grupos de crianças, mas não no grupo Mulheres. Assim, sugerimos que ocorreu um priming de células Th1Th17 em Mães que deram à luz bebês com SZC e em Crianças, independente do desfecho seu clínico. De acordo com a literatura, células Th1Th17 são consideradas patogênicas, com tropismo para o sistema nervoso central. Desta forma, nossos dados encorajam uma profunda investigação sobre o possível envolvimento das células Th1Th17 no desenvolvimento da SZC.

IntroductionA wide variety of viruses can cause rash diseases (RDs) or acute febrile illness (AFIs) in children, adolescents and adults; however, approximately 19% of RD cases and 40% of AFI cases remain without a defined etiology. Parvovirus B19 (B19V) and herpesvirus infection can also cause RD and/or AFI, and in some risk groups, these infections can become persistent (or latent) and may require hospital treatment. Since these infections do not have mandatory reporting, they can be hidden by other diseases, such as those caused by arboviruses (e.g., dengue virus). In this context, the aim of this study was to pursue the differential laboratory diagnoses of B19V and herpesvirus infections in patients with RD and AFI, without a defined etiology, seen in hospitals and/or reference centers for infectious diseases in Rio de Janeiro.MethodsA total of 114 participants were enrolled in the study, including 54 children and 60 adults. B19V infection was assessed by real-time PCR (qPCR) and ELISA (anti-B19V IgM and IgG). EBV was assessed through qPCR, and betaherpesviruses (HCMV, HHV-6 and HHV-7) were assessed through multiplex qPCR. Sociodemographic and clinical data were obtained from the medical record data of these participants.ResultsThe median age of children with RD was 2 years (interquartile range (IQR): 5), and 55.6% were male. Among adults with AFI, the median age was 38 years (IQR: 21), and 56.7% were female. Regarding RD patients, viral prevalence (and load) were 5.5%(104IU/mL), 3.4%(104IU/mL), 5.5%(104IU/mL) and 11.1%(105IU/mL) for B19V, EBV, HCMV and HHV-6 infection, respectively, and in AFI patients they were 6.6%(105IU/mL), 1.6%(103IU/mL), 3.3%(104IU/mL) for B19V, HCMV and HHV-6, respectively. HHV-7 was not detected in RD or AFI patients.ConclusionThese results suggest the importance of including B19V and herpesviruses in the differential laboratory diagnoses for patients with RD and AFI, not only for epidemiological purposes but also for the proper management of the patient.

Abstract Background Staphylococcus aureus and beta-hemolytic streptococci (BHS) diseases disproportionately affect populations in middle/low-income countries. To assess if this disparity is reflected in colonization by these organisms, we compared their colonization frequency among children from different socioeconomic status (SES) communities in a city with high income inequality. Methods Between May–August 2014, we collected nasal and throat swabs to investigate S. aureus and BHS colonization among children who attended private and public pediatric clinics. Patients were classified as high SES, middle/low SES, and slum residents. We investigated the antimicrobial resistance profile, the SCCmec types and the presence of PVL genes among methicillin-resistant S. aureus (MRSA). We also examined the antimicrobial resistance profile and serogroups of BHS. Results Of 598 children, 221 (37%) were colonized with S. aureus, of which 49 (22%) were MRSA. MRSA colonization was higher in middle/low SES (n = 18; 14%) compared with high SES (n = 17; 6%) and slum (n = 14; 8%) residents (p = 0.01). All MRSA strains were susceptible to clindamycin, nitrofurantoin, and rifampin. The highest non-susceptibility frequency (42.9%) was observed to erythromycin. SCCmec type V was only found in isolates from high SES children; types I and II were found only in middle/low SES children. Ten (20%) MRSA isolates carried PVL genes. Twenty-four (4%) children were BHS carriers. All BHS (n = 8) found in high SES children and six (67%) isolates from slum patients belonged to group A. All group B streptococci were from middle/low SES children, corresponding to five (71%) of the seven BHS isolated in this group. BHS isolates were susceptible to all drugs tested. Conclusions Children from different SES communities had distinct bacterial colonization profiles, including MRSA carriage. Public health officials/researchers should consider SES when assessing disease transmission and control measures.

Chikungunya virus (CHIKV) vertical transmission occurs due to maternal viremia in the prepartum. Clinical presentation in neonates can be varied; however, the consequences of intrauterine exposure on the immune response are unclear. Thus, we aimed to analyze inflammatory alterations in children exposed to maternal CHIKV infection. This is a cross-sectional study that included children exposed to maternal CHIKV infection (confirmed by RT-qPCR and/or IgM). Circulant immune mediators were analyzed by a multiplex assay. RESULTS: We included 33 children, with a mean age of 3 ± 2.9 months-old, and 19 (57.6%) were male. Only one child presented neurological alterations. CHIKV-exposed infants showed elevated levels of MIP-1α, MIP-1β, and CCL-2 (p < 0.05). Pro-inflammatory cytokines such as TNFα, IL-6, and IL-7 (p < 0.0001) were also increased. In addition, lower levels of PDGF-BB and GM-CSF were observed in the same group (p < 0.0001). Principal component (PC) analysis highlighted a distinction in the inflammatory profile between groups, where PC explained 56.6% of the alterations. Our findings suggest that maternal exposure to CHIKV can affect the circulating levels of pro-inflammatory cytokines during the infants’ first year of life. The long-term clinical consequences of these findings should be investigated.

Background: Zika virus (ZIKV) infection causes for mild and self-limiting disease in healthy adults. In newborns, it can occasionally lead to a spectrum of malformations, the congenital Zika syndrome (CZS). Thus, little is known if mothers and babies with a history of ZIKV infection were able to develop long-lasting T-cell immunity. To these issues, we measure the prevalence of ZIKV T-cell immunity in a cohort of mothers infected to the ZIKV during pregnancy in the 2016–2017 Zika outbreak, who gave birth to infants affected by neurological complications or asymptomatic ones.Results: Twenty-one mothers and 18 children were tested for IFN-γ ELISpot and T-cell responses for flow cytometry assays in response to CD4 ZIKV and CD8 ZIKV megapools (CD4 ZIKV MP and CD8 ZIKV MP). IFN-γ ELISpot responses to ZIKV MPs showed an increased CD4 and CD8 T-cell responses in mothers compared to children. The degranulation activity and IFN-γ-producing CD4 T cells were detected in most mothers, and children, while in CD8 T-cells, low responses were detected in these study groups. The total Temra T cell subset is enriched for IFN-γ+ CD4 T cells after stimulation of CD4 ZIKV MP.Conclusion: Donors with a history of ZIKV infection demonstrated long-term CD4 T cell immunity to ZIKV CD4 MP. However, the same was not observed in CD8 T cells with the ZIKV CD8 MP. One possibility is that the cytotoxic and pro-inflammatory activities of CD8 T cells are markedly demonstrated in the early stages of infection, but less detected in the disease resolution phase, when the virus has already been eliminated. The responses of mothers' T cells to ZIKV MPs do not appear to be related to their children's clinical outcome. There was also no marked difference in the T cell responses to ZIKV MP between children affected or not with CZS. These data still need to be investigated, including the evaluation of the response of CD8 T cells to other ZIKV peptides.

ABSTRACT The aim of this study was to evaluate the concordance between two versions of the scoring system (2011 and 2019), recommended by the Brazilian Ministry of Health, for the diagnosis of pulmonary tuberculosis (PTB) in children and adolescents. A retrospective descriptive study was performed to assess the medical records of children and adolescents with PTB, in TB units from Brazilian cities located in Rio de Janeiro, Minas Gerais, and Parana States, from January 1 st , 2004, to December 1 st , 2018. Patients aged 0 to 18 years old with a diagnosis of PTB were included. The comparison between the two scoring systems showed a moderate concordance according to the κ coefficient value = 0.625. Fourteen patients showed a reduction in the TB score, going from 30 points in the 2011, to 25 points or less in the 2019 one. Seventy one percent of these 14 patients had radiological changes suggestive of PTB and 86% had tuberculin skin tests greater than 10 mm. The study concluded that a moderate agreement was observed between the 2011 and 2019 scoring systems, with an increase in the number of patients scoring 25 points or less in 2019, which can eventually hinder the diagnosis of PTB.

Abstract INTRODUCTION: The diagnostic accuracy of Xpert MTB/RIF (Xpert) in pulmonary tuberculosis (PTB) in children is lower than in adults. In Brazil, the diagnosis of PTB is based on a diagnostic score system (DSS). This study aims to study the role of Xpert in children and adolescents with PTB symptoms. METHODS: A cross-sectional study was conducted in 3 referral centers to TB. Children and adolescents (0-19 years old) whose respiratory samples were submitted to Xpert were included. Statistical analysis (bivariate and logistic regression) to assess the simultaneous influence of TB-related variables on the occurrence of Xpert detectable in TB cases was done. To evaluate the agreement or disagreement between Xpert results with acid-fast bacillus (AFB) and cultures, κ method was used (significancy level of 5%). RESULTS: Eighty-eight patients were included in the study and PTB occurred in 43 patients (49%) and Xpert was detectable in 21 patients (24%). Adolescents and positive culture results were independent predictive variables of Xpert positivity. DSS sensitivity compared with the final diagnosis of TB was 100% (95% CI, 88.1-100%), specificity was 97.2% (95% CI, 85.5-99.9%). The accuracy of the method was 98.5% (95% CI, 91.7-99.9%). CONCLUSIONS: Xpert contributed to diagnosis in 9% of patients with AFB and in culture negative cases. DSS indicated relevance for this diagnostic approach of intrathoracic TB (ITB) in reference centers for presenting data both with high sensitivity and specificity.

Low levels of parvovirus B19 (B19V) DNA can be detected in the circulation and in different tissue of immunocompetent individuals for months or years, which has been linked to inflammatory diseases such as cardiomyopathy, rheumatoid arthritis, hepatitis, and vasculitis. However, the detection of B19V DNA does not necessarily imply that infectious virions are present. This study aimed to evaluate the method based on the Benzonase® treatment for differentiation between the infectious virions from “naked” DNA in serum and bone marrow (BM) samples to be useful for the B19V routine diagnosis. In addition, we estimated the period of viremia and DNAemia in the sera and bone marrow of nonhuman primates experimentally infected with B19V. Serum samples from ten patients and from four cynomolgus monkeys experimentally infected with B19V followed up for 60 days were used. Most of the human serum samples became negative after pretreatment; however, only decreased viral DNA loads were observed in four patients, indicating that these samples still contained the infectious virus. Reduced B19V DNA levels were observed in animals since 7th dpi. At approximately 45th dpi, B19V DNA levels were below 105 IU/mL after Benzonase® pretreatment, which was not a consequence of active B19V replication. The test based on Benzonase® pretreatment enabled the discrimination of “naked DNA” from B19V DNA encapsidated in virions. Therefore, this test can be used to clarify the role of B19V as an etiological agent associated with atypical clinical manifestations.

Over the past 15 years, and despite many difficulties, significant progress has been made to advance child and adolescent tuberculosis (TB) care. Despite increasing availability of safe and effective treatment and prevention options, TB remains a global health priority as a major cause of child and adolescent morbidity and mortality—over one and a half million children and adolescents develop TB each year. A history of the global public health perspective on child and adolescent TB is followed by 12 narratives detailing challenges and progress in 19 TB endemic low and middle-income countries. Overarching challenges include: under-detection and under-reporting of child and adolescent TB; poor implementation and reporting of contact investigation and TB preventive treatment services; the need for health systems strengthening to deliver effective, decentralized services; and lack of integration between TB programs and child health services. The COVID-19 pandemic has had a significant negative impact on case detection and treatment outcomes. Child and adolescent TB working groups can address country-specific challenges to close the policy–practice gaps by developing and supporting decentral ized models of care, strengthening clinical and laboratory diagnosis, including of multidrug-resistant TB, providing recommended options for treatment of disease and infection, and forging strong collaborations across relevant health sectors.

Abstract Background Despite great progress made in methods to prevent mother-to-child transmission of HIV (MTCT), delivery and uptake of these measures remains a challenge in many countries. Although the Brazilian Ministry of Health aimed to eliminate MTCT by 2015, infection still occured in 15–24% of infants born to HIV-infected mothers. We sought to identify remaining factors that constrain MTCT elimination. Methods We conducted a retrospective, matched case-control study by reviewing hospital charts of infants born to HIV-infected mothers between 1997 and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan area. Cases were defined as HIV-exposed children with two positive HIV tests before 18 months of age; controls were defined as HIV-exposed children with two negative HIV tests before 18 months of age. We performed bivariate and MTCT cascade analyses to identify risk factors for MTCT and gaps in prevention services. Results We included 435 infants and their mothers (145 cases, 290 controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that cases were less likely to complete all individual measures in the antenatal, delivery, and postnatal period (p

High levels of T helper 17 cell (Th17)-related cytokines have been shown in acute Zika virus (ZIKV) infection. We hypothesized that the high levels of Th17-related cytokines, associated with a regulatory environment during pregnancy, create a favorable milieu for the differentiation of CD4+Th17 cells. We present data from a cross-sectional study on mothers who confirmed ZIKV infection by qRT-PCR and their children. We also recruited non-pregnant women infected with ZIKV in the same period. ZIKV infection occurred between 2015 and 2017. We collected samples for this study between 2018 and 2019, years after the initial infection. We highlight that, after in vitro stimulation with ZIKV CD4 megapool (ZIKV MP), we found a lower frequency of IL-17-producing CD4+ T cells (Th17), especially in the mothers, confirmed by the decrease in IL-17 production in the supernatant. However, a higher frequency of CD4+ IL-17+ IFN-γ+ T cells (Th1Th17) responding to the ZIKV MP was observed in the cells of the mothers and children but not in those of the non-pregnant women. Our data indicate that the priming of CD4 T cells of the Th1Th17 phenotype occurred preferentially in the mothers who gave birth to children with CZS and in the children.

ImportanceNon-invasive techniques for retrieving ocular surface cells from babies infected by zika virus (ZIKV) during the gestational period remain to be determined.ObjectivesThe aim of this study was to describe an optimized impression cytology method for the isolation of viable cells from Zika infected babies with and without Congenital Zika Syndrome (CZS) in satisfactory amount and quality to enable easy adoption in the field and application in the context of genomic and molecular approaches.Design, Settings, and ParticipantsOcular surface samples were obtained with a hydrophilic nitrocellulose membrane (through optimized impression cytology method) from twelve babies referred to the Pediatric Service of the Antonio Pedro Hospital, Universidade Federal Fluminense (UFF), Niteroi, Rio de Janeiro, Brazil. After an authorized written informed consent from the parents, samples were collected from both eyes of 12 babies (4 babies with maternal ZIKV exposure during gestation and presence of clinical signs which included ocular abnormalities and microcephaly; 4 babies with maternal ZIKV exposure during gestation but no clinical signs; and 4 unaffected control babies with negative PCR for Zika virus and without clinical signs). Cells were used for microscopy analyses and evaluated for their suitability for downstream molecular applications in transcriptomic and proteomic experiments.ResultsOur optimized impression cytology protocol enabled the capture of a considerable number of viable cells. The microscopic features of the conjunctival epithelial cells were described by both direct analysis of the membrane-attached cells and analysis of cytospinned captured cells using several staining procedures. Epithelial basal, polyhedral and goblet cells were clearly identified in all groups. All cases of ZIKV infected babies showed potential morphological alterations (cell keratinization, pyknosis, karyolysis, anucleation, and vacuolization). Molecular approaches were also performed in parallel. Genomic DNA and RNA were successfully isolated from all samples to enable the establishment of transcriptomic and proteomic studies.Conclusions and RelevanceOur method proved to be a suitable, fast, and non-invasive tool to obtain ocular cell preparations from babies with and without Zika infection. The method yielded sufficient cells for detailed morphological and molecular analyses of samples. We discuss perspectives for the application of impression cytology in the context of ZIKV studies in basic and clinical research.

There have been reports of neurological abnormalities associated with the Zika virus (ZIKV), such as congenital Zika syndrome (CZS) in children born to mothers infected during pregnancy. We investigated how the immune response to ZIKV during pregnancy is primed and conduct a thorough evaluation of the inflammatory and cytotoxic profiles as well as the expression of CCR5 and CX3CR1. We compared the reactivity of T cells to ZIKV peptides in convalescent mothers infected during pregnancy. The child’s clinical outcome (i.e., born with or without CZS) was taken to be the variable. The cells were stimulated in vitro with ZIKV peptides and evaluated using the ELISPOT and flow cytometry assays. After in vitro stimulation with ZIKV peptides, we observed a tendency toward a higher Interferon gamma (IFN-γ)-producing T cell responses in mothers who had asymptomatic children and a higher CD107a expression in T cells in mothers who had children with CZS. We found a higher frequency of T cells expressing CD107a+ and co-expressing CX3CR1+CCR5+, which is much clearer in the T cells of mothers who had CZS children. We suggest that this differential profile influenced the clinical outcome of babies. These data need to be further investigated, including the evaluation of other ZIKV peptides and markers and functional assays.

Este estudo tem como objetivo avaliar o uso da terapia antirretroviral combinada em crianças e adolescentes com AIDS. Foram captados 247 resumos nos portais PubMed e LILACS, publicados entre 1983 e 2013, sendo utilizados 69 artigos para as referências bibliográficas. A atenção atribuída às pesquisas na faixa etária pediátrica durante os trinta anos de epidemia de AIDS se justifica por características imunológicas próprias, sendo a progressão da AIDS mais rápida em crianças que em adultos. Pesquisas recentes abordam estratégias de intervenção medicamentosa de alta potência antes do aparecimento dos sintomas iniciais. A introdução precoce da terapia antirretroviral combinada foi implantada com eficácia e segurança em populações com poucos recursos fixos, com melhora significativa da sobrevida desses pacientes. O desafio atual é lidar com uma doença crônica com intercorrências agudas. Novas pesquisas serão necessárias, atentando para as especificidades populacionais e particularizando as necessidades individuais dos pacientes pediátricos.

The use of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected patients has reduced the number of acquired immune deficiency syndrome-related deaths worldwide. This study assessed the impact of HAART on the survival and death rates of vertically HIV-infected children and adolescents in Belo Horizonte, Brazil. Data were obtained from a historic cohort of vertically HIV-infected children and adolescents aged zero-19 years old who were admitted from March 1989-December 2004 and were followed until June 2006. Patients who used HAART were included if they were treated for at least 12 weeks. Of 359 patients, 320 patients met the inclusion criteria. The overall mortality rate was 9.7% [31/320; 95% confidence interval (CI): 6.0-13%]. The median survival for the non-HAART and HAART groups was 31.5 and 55.9 months, respectively (log rank = 22.11, p < 0.0001). In the multivariate analysis, the statistically significant variables were HAART and the weight-for-age Z score < -2, with HAART constituting a protective factor [relative risk (RR): 0.13; CI 95%: 0.05-0.33] and malnutrition constituting a risk factor (RR: 3.44; CI 95%: 1.60-7.40) for death. The incidence of death was 5.1/100 person-years in the non-HAART group and 0.8/100 person-years in the HAART group (p < 0.0001).

Objective: Compare the anti-T. gondii IgG titer between HIV-1 infected and non HIV-1 infected pregnant women and report three cases of congenital toxoplasmosis resulting from reactivation of infection during pregnancy of HIV-1 infected women. Methods: This study was conducted among 2,270 pregnant women with chronic Toxoplasma gondii infection (absence of IgM and presence of IgG), including 82 HIV-1 infected and 2,188 non-infected women. Results: The average anti-T. gondii IgG titer was 127 for the 2,188 non-HIV-1 infected women, and 227 for the 82 HIV-1-infected women (p = 0,007). These results suggested that higher anti-T. gondii IgG titers in HIV-1-infected pregnant women may not be indicative of an elevated risk for fetal infection. In this study three cases of congenital toxoplasmosis that resulted from infection reactivation during pregnancy of HIV-1-infected women were manifested by fetal death, symptomatic infection, and infant without symptoms, respectively. In two of these women, a ten-fold increase in IgG levels above used cutoff was observed (2,320 UI/mL and 3,613 UI/mL, respectively). In the third pregnant women anti-T. gondii IgG titers during pregnancy did not rise despite the occurrence of congenital toxoplasmosis (204; 198; 172 UI/mL). Conclusions: Congenital toxoplasmosis resulting reactivation of infection during pregnancy in the studied group leads us to believe that it is a public health problem, especially in our population, in which seroprevalence of T. gondii infections is high. These findings also suggest that special attention is necessary during pregnancy, because the serologic diagnosis may not be indicative of toxoplasmosis reactivation. Keywords: Toxoplasma, Toxoplasmosis, congenital, HIV infections

ABSTRACT Tuberculosis continues to be a public health priority in many countries. In 2015, tuberculosis killed 1.4 million people, including 210,000 children. Despite the recent progress made in the control of tuberculosis in Brazil, it is still one of the countries with the highest tuberculosis burdens. In 2015, there were 69,000 reported cases of tuberculosis in Brazil and tuberculosis was the cause of 4,500 deaths in the country. In 2014, the World Health Organization approved the End TB Strategy, which set a target date of 2035 for meeting its goals of reducing the tuberculosis incidence by 90% and reducing the number of tuberculosis deaths by 95%. However, to achieve those goals in Brazil, there is a need for collaboration among the various sectors involved in tuberculosis control and for the prioritization of activities, including control measures targeting the most vulnerable populations. Children are highly vulnerable to tuberculosis, and there are particularities specific to pediatric patients regarding tuberculosis development (rapid progression from infection to active disease), prevention (low effectiveness of vaccination against the pulmonary forms and limited availability of preventive treatment of latent tuberculosis infection), diagnosis (a low rate of bacteriologically confirmed diagnosis), and treatment (poor availability of child-friendly anti-tuberculosis drugs). In this review, we discuss the epidemiology, clinical manifestations, and prevention of tuberculosis in childhood and adolescence, highlighting the peculiarities of active and latent tuberculosis in those age groups, in order to prompt reflection on new approaches to the management of pediatric tuberculosis within the framework of the End TB Strategy.

OBJECTIVE: Compare the anti-T. gondii IgG titer between HIV-1 infected and non HIV-1 infected pregnant women and report three cases of congenital toxoplasmosis resulting from reactivation of infection during pregnancy of HIV-1 infected women. METHODS: This study was conducted among 2,270 pregnant women with chronic Toxoplasma gondii infection (absence of IgM and presence of IgG), including 82 HIV-1 infected and 2,188 non-infected women. RESULTS: The average anti-T. gondii IgG titer was 127 for the 2,188 non-HIV-1 infected women, and 227 for the 82 HIV-1-infected women (p = 0,007). These results suggested that higher anti-T. gondii IgG titers in HIV-1-infected pregnant women may not be indicative of an elevated risk for fetal infection. In this study three cases of congenital toxoplasmosis that resulted from infection reactivation during pregnancy of HIV-1-infected women were manifested by fetal death, symptomatic infection, and infant without symptoms, respectively. In two of these women, a ten-fold increase in IgG levels above used cutoff was observed (2,320 UI/mL and 3,613 UI/mL, respectively). In the third pregnant women anti-T. gondii IgG titers during pregnancy did not rise despite the occurrence of congenital toxoplasmosis (204; 198; 172 UI/mL). CONCLUSIONS: Congenital toxoplasmosis resulting reactivation of infection during pregnancy in the studied group leads us to believe that it is a public health problem, especially in our population, in which seroprevalence of T. gondii infections is high. These findings also suggest that special attention is necessary during pregnancy, because the serologic diagnosis may not be indicative of toxoplasmosis reactivation.

Resumo Este artigo analisa o desenvolvimento de uma pesquisa no campo da Epidemiologia, na interface com a psicologia histórico- cultural, que teve como cenário uma comunidade urbana. A pesquisa pretendia comparar a carga das doenças relacionadas ao diabetes mellitus, a fim de, posteriormente, promover uma prática em saúde, o que significa uma divisão entre diagnóstico e intervenção. Entretanto, durante o processo, uma pesquisa, alternativa a este modelo diagnóstico, foi sendo produzida no processo dialógico entre os envolvidos. Esta prática - nomeada de pesquisa-intervenção - trouxe à cena o caráter construtivo do conhecimento e produziu “zonas de sentido”, que engendraram formas novas para a pesquisa e para a prática em saúde. Estas transformações exigiram também novos percursos epistemológicos, o que nos aproximou da psicologia histórico-cultural de Vigotski, da pedagogia de Freire e da filosofia da linguagem de Bakhtin

CC398 is a livestock-associated Staphylococcus aureus. However, it has also been isolated from humans with no previous contact with livestock. A surveillance of methicillin-resistant S. aureus colonisation among children attending public day care centres and hospitals in Niterói and Rio de Janeiro, Brazil, between 2011 and 2013, resulted in the isolation of six cases of CC398 from individuals with no previous exposure to livestock. These isolates showed a high frequency of the erm(C) gene (4/6, 66.7%) with induced resistance to clindamycin, and a relatively high frequency of SEs and lukS/lukF genes. These results suggest the emergence of a non-LA-CC398 in Brazil.

OBJECTIVE: The present literature review aims to highlight gaps in the treatment of preventative mother-to-child HIV transmission and the risk factors in Brazil. METHODS: Among the 425 articles identified in SciELO and PubMed searches, 59 articles published between 1994 and 2016 were selected for reading and data extraction, and 33 articles were included in the present review. RESULTS: The rates of vertical HIV transmission described in the studies varied widely, from 1.8% to 27.8%, with a significant reduction over the years. However, recent rates were also found to be variable in different regions of Brazil, and despite the significant reduction in mother-to-child transmission, many gaps remain in prevention services. A failure to attend prenatal care is the main factor associated with the increased risk of vertical transmission of HIV, hindering early maternal diagnosis and the completion of preventative measures during the prenatal period and, often, the peripartum and postnatal periods. A small number of studies discussed the sociodemographic factors, including a low level of education for pregnant women and the inadequacies of health services, such as difficulties scheduling appointments and undertrained staff, associated with vertical transmission. As such, the current challenge is to better define the sociodemographic and infrastructural factors that increase the risk of mother-to-child transmission of HIV to provide the necessary investments to promote an earlier inclusion of these populations in prevention services. CONCLUSIONS: This review may serve as a guide for future programs to focus efforts on the prevention of vertical HIV transmission.

Abstract Listeria is an unusual pathogen that causes neonatal infection with high morbidity and mortality. We present the case of a premature newborn whose mother had a rash during pregnancy; the newborn had severe early sepsis because of Listeria monocytogenes and histopathologically suggestive findings of the placenta. Obstetricians and neonatologists should suspect listeriosis in cases with compatible epidemiological history, clinical features, and examination findings of the placenta.

BackgroundVaccination schedules, as well as their effectiveness and contraindications, need to be evaluated regularly, especially in specific situations. Congenital Zika Syndrome (CZS) is a severe condition that results in extensive functional and neurological impairment of fetuses and newborns due to Zika virus tropism for fetal neural progenitor cells. Down Syndrome (DS) is the leading genetic cause of intellectual disability. The immune impairment in DS has already been described, but little is known about the immune response of CZS children. Thus, CZS and DS are specific conditions that can be considered for a reassessment of the available immunizations. Here, we carried out serological analyses of attenuated vaccines-induced antibodies for measles, rubella, and yellow fever viruses in children aged 2–7, grouped into asymptomatic controls, DS children, and CZS children.MethodsPlasma samples were taken, and vaccination records were compiled during clinical follow-up. Enzymatic immunoassays for quantifying anti-measles and anti-rubella IgG were performed to assess the response to the Measles, Mumps, and Rubella (MMR) vaccine. Plaque Reduction Neutralization Test (PRNT) was performed to investigate neutralizing antibodies in response to the Brazilian vaccine strain of yellow fever (YF-17DD).ResultsWe highlight similar levels of anti-measles IgG and neutralizing antibodies for YF-17DD among CZS, DS, and asymptomatic children, although low positivity of measles data was seen in the three groups. In DS children, the 2–4-year-old group had an increased level of anti-measles IgG compared to the older group of children aged five to seven years. Lower anti-rubella IgG levels were observed in CZS and DS children compared to asymptomatic children. For anti-rubella IgG, the good performance of vaccination in asymptomatic children is due to younger ones rather than older ones.ConclusionsThere were no reports of adverse events after the use of the MMR and YF-17DD indicating that CZS and DS could continue to receive these vaccines, but our data draws attention to the necessity of monitoring the vaccination response in CZS and DS children over time and the possible need to adhere to national measles vaccination campaigns. Scientific research needs to continue to help develop appropriate CZS and DS health guidelines.