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To assess the clinical and radiographic characteristics of hip joint deformities in children with congenital Zika syndrome (CZS), and the evolution of hip joint deformities in affected infants for the first three years of life.This prospective observational study evaluated orthopedic clinical examinations performed every 3 months to assess hip flexion and extension, lateral and medial rotation, abduction and adduction, as well as lower limb muscle length and tone. The biannual radiograph comprised anteroposterior panoramic pelvic radiographs with the lower limbs in extension. Percentage of migration was used as a radiographic study tool to measure and evaluate linear hip displacement.From November 2018 to March 2020, we followed 30 children with CZS, of which 15 (50%) had normal pelvic radiographs on admission; five (33.3%) developed hip displacement by the second radiograph exam. During follow up radiographic examinations, 20/30 (66.7%) children were diagnosed with hip displacement and/or dislocation of at least one side, and 10/30 (33.3%) remained normal. Among 30 affected patients, 13 (43.3%) had hip displacement on the right side and 9 (30%) on the left side. Logistic regression analysis revealed that spasticity (p=0.0033; OR=15.9) and ophthalmologic abnormalities (p=0.0163; OR=16.9) were associated with hip dislocation during follow up.Pelvic radiographic follow up for all children with CZS will complement physical examination, diagnosis, and monitoring for hip joint deformities.

Background In Brazil, some local city government’s adopted several measures, which probably had a positive impact on COVID-19 control. Objective To report the distribution of COVID-19 cases in Brazil, Rio de Janeiro state and Niterói city. In parallel, we aimed to demonstrate the preventive strategies adopted by Niterói city. Method Data provided by the Brazilian Ministry of Health and Municipal Health Foundation of Niterói were used to report COVID-19 cases and deaths. For some analysis, data were grouped by week and normalized for 100,000 inhabitants. Results By July 18th, 2020, Brazil reported 2,074,860 cases and 78,772 deaths and Rio de Janeiro state registered 135,230 cases and 11,919 deaths; both still presenting ascendant curves for COVID-19 deaths. In contrast, the rate of new deaths per 100,000 inhabitants is consistently lower in Niterói city. Importantly, we estimated that 712 deaths were prevented by the measures adopted by Niterói city, in comparison to which was observed in Rio de Janeiro. Conclusion The early preventive measures adopted in Niterói city were effective in reducing both the viral spread and rate of deaths. In this regard, this discussion could be relevant for making future decisions during the COVID-19 outbreak in Brazil.

Zika virus (ZIKV) is a member of the Flavivirus family. ZIKV infection ranges from asymptomatic to a mild disease in adults. However, in 2015, ZIKV infection became a public health emergency in the Americas associated with neurological alterations such as Guillain-Barré syndrome (GBS) in adults and congenital zika syndrome (CZS). By blocking type I IFN interferon signaling pathways, ZIKV evades the immune system and infects cells expressing the T cell immunoglobulin mucin domain-1 (TIM-1) and TAM (Tyro3, AXL, and Mer) receptors, such as neural progenitor cells. Moreover, ZIKV seems to orchestrate a process of astrocytic hypoxia that leads to the production of reactive oxygen species (ROS), mitochondrial DNA (mtDNA) fragmentation, and apoptosis. In recent decades, the active participation of mitochondria in the immuno-inflammatory response has been reported in several pathologies. In this context, mtDNA seems to have an essential role in triggering the innate immune response by activating inflammasomes, activating the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway, and also activating toll-like receptors that lead to IFN production and viral clearance. Here, we present an overview of some mechanisms of inflammatory response present in ZIKV infection, which contributes to mitochondrial dysfunction, mtDNA release, and tissue damage.

Since distinguishing pulmonary (PTB) from latent tuberculosis (LTBI) in pediatric patients remains a challenge, we aimed to investigate the efficacy of immune mediators in diagnosing PTB and LTBI in this population. In this cross-sectional study performed with children and adolescents, serum levels of 20 biomarkers were assessed and data were analyzed according to age groups. We included 65 participants (PTB, n = 28 and LTBI, n = 37). Overall, levels of TNF-α, IL-1Ra, IL-6, IL-17A, VEGF, MMP-1, and procalcitonin were significantly higher (P 0.05) in adolescents and children10 years-old with PTB. Also, principal component analysis (PCA) showed that immune mediators were able to distinguish PTB from LTBI. VEGF and IL-1Ra presented the highest area under the curve (AUC) values, both separately (AUC 0.890 and 0.785) and combined (AUC 0.99). Taken together, we showed that VEGF and IL-1Ra are promising biomarkers to distinguish PTB from LTBI in pediatric patients, especially in children5 years-old.

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.

Objective To better understand the clinical spectrum and course of congenital Zika syndrome (CZS) during the first 18 months of life of children whose mothers had rash during pregnancy. Methods This longitudinal observational study evaluated the clinical progress from birth until 18 months of life of children of mothers who developed rash during or up to 3 months before gestation. Maternal rash occurred from November 2015 to May 2017. The study subjects were divided into three groups: children whose mothers tested positive by RT-qPCR for Zika virus (ZIKV) (Group 1), children whose mothers tested negative by RT-qPCR for ZIKV (Group 2), and children whose mothers did not undergo any testing for ZIKV (Group 3) but tested negative for other congenital infections. Results Between April 2016 and July 2018, we studied 108 children: 43 in Group 1, 26 in Group 2 and 39 in Group 3. The majority of children were admitted into the study within 6 months of life. CZS was diagnosed in 26 children, equally distributed in Groups 1 and 3. Of 18 children with microcephaly, 6 were in Group 1 (1 postnatal) and 12 were in Group 3 (5 postnatal). Maternal rash frequency was 10 times higher during the first trimester than in the other trimesters (OR: 10.35; CI 95%: 3.52–30.41). CZS was diagnosed during the follow-up period in 14 (54%) cases. Developmental delays and motor abnormalities occurred in all children and persisted up to 18 months. Epilepsy occurred in 18 (69%) of the cases. Conclusions Infants born of mothers exposed to ZIKV during pregnancy showed progression of developmental, motor and neurologic abnormalities even if they were born asymptomatic. Continued postnatal monitoring of such newborns is necessary to preclude disability-associated complications.

Severe cases of coronavirus disease 2019 (COVID-19) have increased risk for acute kidney injury (AKI). The exacerbation of the immune response seems to contribute to AKI development, but the immunopathological process is not completely understood.To analyze levels of circulant immune mediators in COVID-19 patients evolving with or without AKI. We have also investigated possible associations of these mediators with viral load and clinical outcomes.This is a longitudinal study performed with hospitalized patients with moderate to severe COVID-19. Serum levels of 27 immune mediators were measured by a multiplex immunoassay. Data were analyzed at two timepoints during the follow-up: within the first 13 days of the disease onset (early sample) and from the 14th day to death or hospital discharge (follow-up sample).We studied 82 COVID-19 patients (59.5 ± 17.5 years, 54.9% male). Of these, 34 (41.5%) developed AKI. These patients presented higher SARS-CoV-2 viral load (P = 0.03), higher frequency of diabetes (P = 0.01) and death (P = 0.0004). Overall, AKI patients presented significantly higher and sustained levels (P 0.05) of CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IFN-γ, IL-2, IL-6, TNF-α, IL-1Ra, IL-10 and VEGF. Importantly, higher levels of CCL-2, CXCL-10, IL-2, TNF-α, IL-10, FGFb, and VEGF were observed in AKI patients independently of death. ROC curves demonstrated that early alterations in CCL-2, CXCL-8, CXCL-10, IFN-γ, IL-6, IL-1Ra and IL-10 show a good predictive value regarding AKI development. Lastly, immune mediators were significantly associated with each other and with SARS-CoV-2 viral load in AKI patients.COVID-19 associated AKI is accompanied by substantial alterations in circulant levels of immune mediators, which could significantly contribute to the establishment of kidney injury.

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.

Introduction: Studies suggest the association between antibody production and the severity of coronavirus disease 2019 (Covid-19). Objectives: To evaluate the concentrations of immunoglobulins class A (IgA) and class G (IgG) during the hospitalization period of Covid-19 patients according to the outcome (survival vs death). Materials and methods: Patients with severe acute respiratory syndrome of coronavirus 2 (Sars-CoV-2) infection confirmed by reverse transcriptase reaction followed by polymerase chain reaction (RT-PCR) were included in this prospective study. Samples were obtained weekly during the follow-up of individuals, considering symptom onset. Titers of anti-Sars-CoV-2 IgA and IgG were measured using a commercial immunoassay. Correlations between IgA/IgG and cycle threshold (Ct) values for N1 and N2 target genes were also assessed. Results: We studied 55 Covid-19 patients (59.7±16.2 years, 63.6% male), of which 28 (50.9%) died. We observed IgA and IgG positivity (IgA+ and IgG+) in 90.9% and 80% of patients, respectively. The highest IgA+ frequency was observed at weeks 2 and 3 and the highest IgG+ at weeks 3 and 4. It is important to note that patients who died presented lower IgA titers in the first two weeks (p < 0.05); however, a significant increase in IgA levels was observed in the subsequent weeks. Lastly, we identified that significant correlations between Ct values and immunoglobulins levels, both IgA and IgG were correlated with Ct N2 in patients who died. Conclusion: Our results suggest that lower IgA titers in early Covid-19, which is associated with lower Ct values, may indicate patients at higher risk for death.

Objective To evaluate auditory manifestations in children born to mothers who had exanthema during pregnancy, suspected to have been exposed to the Zika virus (ZIKV). Study design Prospective observational. Setting Tertiary referral center. Patients Children born in Rio de Janeiro, Brazil, between April 2016 and September 2017, who were referred for newborn hearing screening (NHS). Intervention The NHS was performed by the automated brainstem auditory-evoked potential test at an intensity of 30 dBHL (decibels Hearing Level) with the result presented as "PASS/FAIL." A follow-up test was performed 6 months after the first examination. Main outcome measures Hearing outcomes by audiological assessment. Results Ninety-eight children were recruited and 78 underwent the NHS test. In the first evaluation, the FAIL NHS result was observed in 4 of the 78 children. Three were diagnosed with sensorineural hearing loss and one had conductive loss. Including the first and second evaluation, the frequency of audiological alterations was 5.1%. Of the four children diagnosed with hearing loss, two were carriers of ZIKV, one had suspected ZIKV infection, and one was asymptomatic with confirmed exposure to the virus. There was no progression of hearing loss or other hearing abnormality in the children by the time of the second evaluation. The group of nonexposed children (negative quantitative reverse transcription polymerase chain reaction for ZIKV) showed no hearing loss. Conclusion Uni or bilateral sensorineural hearing loss was diagnosed in asymptomatic children at birth. These observations highlight the importance of periodic follow-up of patients with congenital Zika syndrome to better understand their long-term auditory clinical outcome.

Paralelo à pandemia de COVID-19, Brasil continuou a enfrentar doenças tropicais como a Dengue. Mas, segundo os Boletins Epidemiológicos, os casos de Dengue no Brasil em 2020 foram subnotificados. O objetivo deste estudo é identificar a frequência de coinfecções por SARS-CoV-2 e DENV e avaliar a gravidade das coinfecções em relação às monoinfecções. Amostras de plasma de 143 pacientes COVID-19 de 2020, 15 doadores saudáveis e 15 pacientes com infecção por DENV de 2013 foram avaliados. Ensaios imunoenzimáticos utilizando testes comerciais foram realizados: Anti-SARS-CoV-2 IgA e IgG (Euroimmun), proteína NS1 do DENV (Platelia), anti-DENV IgM e IgG (Euroimmun). Dentre os doadores saudáveis foi detectado 75% de IgG anti-DENV; dentre os COVID-19, 75,9% IgA anti SARS-CoV-2, 66,7% IgG anti SARS-CoV-2, 80% IgG anti-DENV e por fim, IgM anti-DENV em 6 (4%) casos; dentre os casos confirmados de Dengue, IgA anti SARS-CoV-2 foi detectado em 1 caso (8,3%), IgG anti-SARS-CoV-2 em nenhum caso, NS1 de DENV em 41,7% e IgM anti-DENV em 33,3%. De acordo com o desfecho clínico, a presença ou não de sinais/sintomas no momento da coleta da amostras, os pacients COVID-19 foram reagrupados em brandos/moderados, graves, óbitos e aqueles já recuperados dos sinais/sintomas. Os 6 casos de COVID-19/Dengue também foram avaliados separadamente. Observamos que idosos são maioria em COVID-19 graves e óbitos; mulheres são maioria dos COVID-19 recuperados; tosse é mais frequente em COVID-19; cefaléia, mialgia/artralgia e vômito são mais frequentes na Dengue; pacientes COVID-19/Dengue foram aqueles com alterações vasculares. As DO IgA anti-SARS-CoV-2 foram mais elevadas nos COVID-19 graves, óbitos e COVID-19/Dengue comparados aos doadores saudáveis e pacientes Dengue; as DO IgG anti-SARS-CoV-2 foram mais elevadas nos COVID-19 comparados aos doadores saudáveis e pacientes Dengue; as DO IgA e IgG anti SARS-CoV-2 foram maiores nos COVID-19 óbitos comparado aos recuperados; COVID-19 recuperados ainda mantém níveis de detecção de IgA e IgG anti-SARS-CoV-2 detectáveis. Há diferenças clínicas, demográficas e de detecção de anticorpos anti-SARS-CoV-2 entre pacientes COVID-19 de acordo com o desfecho clínico e dias da doença. Até o momento, 6% de casos de COVID-19 com sugestiva infecção recente por DENV foram identificados. Os casos de coinfecção SARS-CoV-2/DENV estão sendo confirmados por RT-PCR DENV e esperamos a partir desses resultados, tirar mais conclusões.

Introduction: Human cytomegalovirus is a major cause of morbidity in kidney transplant patients. Objectives: We aimed to study viral replication and serological response in the first months post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy and correlate the findings with the clinical course of Human cytomegalovirus infection. Patients and methods: Independent from the clinical strategy adopted for managing Human cytomegalovirus infection, prophylaxis versus preemptive therapy, the pp65 antigenemia assay and serological response were assessed on the day of transplantation, and then weekly during the first three months of post-transplant. Results: From the 32 transplant recipients, 16 were positive for pp65 antigenemia, with a similar incidence rate in each group. There were no positive results in the first three weeks of monitoring; the positivity rate peaked at week eight. There was a trend for a higher and earlier frequency of positivity in the universal prophylaxis group in which the course of the Human cytomegalovirus infection was also more severe. Despite the differences in clinical picture and in the initial immunosuppressant schedule, the serological response was similar in both groups. Conclusion: Routine monitoring during the first three post-transplant months has a positive impact on the early detection of Human cytomegalovirus viral replication allowing for timely treatment in order to reduce morbidity of the disease. The strategy of universal therapy employing intravenous ganciclovir was associated to a worse clinical course of the Human cytomegalovirus infection suggesting that the use of >10 cells/2 × 105 leukocytes as a cut-off in this setting may be inappropriate. Keywords: Cytomegalovirus, pp65 antigenemia, Kidney transplant, Universal prophylaxis, Preemptive therapy

Introduction Typical symptoms of primary Zika virus infection are not specific and share similarities with other arbovirus infections such as dengue fever and chikungunya. As acute infection can be asymptomatic in up to 73% of cases, infants with microcephaly represent a diagnostic challenge for pediatricians. We describe the frequency of congenital Zika syndrome (CZS) in Brazilian children born to asymptomatic pregnant mothers and its differential diagnosis. Methods This longitudinal, observational study was conducted on children with suspected CZS whose mothers did not report rash during pregnancy, referred to the reference hospital in a metropolitan area of ​ Rio de Janeiro, Brazil. The diagnosis of suspected CZS was based on Brazilian Ministry of Health protocol. Results Forty-three (17%) of 246 referred children were born to mothers without rash history during pregnancy. Thirteen (30%) of 43 children met the Brazilian Ministry of Health criteria for CZS, all with microcephaly (two post-natal). The other children included 11 cases with post-natal microcephaly due to hypoxic-ischemic encephalopathy (6), non-progressive encephalopathy of unknown etiology (2), microcephaly under investigation (2) and congenital toxoplasmosis (1); 17 children were misdiagnosed with microcephaly and progressed with normal head circumference during the follow-up period; one child was included because of epidemiological link and one was loss to follow-up. All children who underwent laboratory investigation for ZIKV infection during neonatal period had negative RT-qPCR tests. Conclusion We emphasize the increasing importance of CZS in differential diagnosis of microcephaly at birth or post-natal period. Detailed clinical investigation assisted by neuroimaging tests may clarify the diagnosis of CZS when laboratory tests are not available during the acute phase of the disease.

Background Arboviruses (Zika, dengue and chikungunya) represent a major risk for pregnant women, especially because their vertical transmission can lead to neurological damage in newborns. Early diagnosis can be difficult due to similar clinical presentation with other congenital infections that are associated with congenital abnormalities. Objectives To investigate the circulation of arboviruses and other pathogens responsible for congenital infections, reporting clinical aspects and geographic distribution of maternal rash in a metropolitan region of Rio de Janeiro (Brazil). Methods Cross-sectional study with pregnant women presenting rash attended at the Exanthematic Diseases Unit (Niteroi, Rio de Janeiro) from 2015 to 2018. Diagnosis of arboviruses was performed by real-time PCR (RT-qPCR) and laboratorial screening for syphilis, toxoplasmosis, rubella, cytomegalovirus and HIV was assessed. Demographic data was used for georeferencing analysis. Findings We included 121 pregnant women, of whom Zika virus was detected in 45 cases (37.2%), chikungunya in 33 (27.3%) and dengue in one (0.8%). Five patients presented syphilis, and we observed one case each of listeria, cytomegalovirus, and a syphilis-toxoplasmosis case. Similarity of clinical symptoms was observed in all groups; however, 84.8% of patients with chikungunya presented arthralgia. Following the decline of Zika cases, chikungunya infection was mostly observed during 2017–2018. Considering pregnant women infected with arboviruses and other infections, 41% resided in urban slums, mostly in Niteroi. Main conclusions Simultaneous circulation of arboviruses and other agents responsible for congenital infections were observed; however, we did not identify co-infections between arboviruses. In this scenario, we emphasize the importance of adequate prenatal care to provide an accurate diagnosis of maternal rash.

Urine monitoring programs represent an important strategy for early diagnosis of reactivation of BK polyomavirus (BKV) in kidney transplant recipients. This study analyzes a BKV urine screening model in kidney transplant patients.Urinary screening for BKV reactivation was performed by urinary decoy cell and polymerase chain reaction (PCR) tests in samples from 32 consecutive kidney transplant patients, collected in a 6-month follow-up period. PCR in plasma samples and BKV immunohistochemical studies to assess BKV renal disease, if a kidney biopsy was indicated, were performed.The urinary screening for BKV among 32 renal receptors was positive in 18 patients (56%) by the concomitant use of the decoy cells and/or qualitative PCR at some time during the study period. Transfusion before transplantation was significantly associated with urinary decoy cell positive screening (odds ratio = 11; 95% confidence interval = 1.47 to 82.4; P .05); and so was male sex (odds ratio = 2.02; 95% confidence interval = 1.07 to 3.83; P .05). The clinical management of screening positive cases consisted of decreasing or changing the immunosuppression regimen. Sixteen renal biopsies were performed. Immunohistochemistry for SV40 T antigen was negative in all biopsies. After 1 year of follow-up, no patient developed BKV-associated nephropathy, and there was no difference in renal function between patients positive and negative for BKV urinary screening.Early urinary monitoring is effective in detection of BKV replication and represents a good strategy to minimize the deleterious effects caused by the presence of the virus on preservation of graft function.