Epidemiological and genomic investigation of chikungunya virus in Rio de Janeiro state, Brazil, between 2015 and 2018

Since 2014, Brazil has experienced an unprecedented epidemic caused by chikungunya virus (CHIKV), with several waves of East-Central-South-African (ECSA) lineage transmission reported across the country. In 2018, Rio de Janeiro state, the third most populous state in Brazil, reported 41% of all chikungunya cases in the country. Here we use evolutionary and epidemiological analysis to estimate the timescale of CHIKV-ECSA-American lineage and its epidemiological patterns in Rio de Janeiro. We show that the CHIKV-ECSA outbreak in Rio de Janeiro derived from two distinct clades introduced from the Northeast region in mid-2015 (clade RJ1, n = 63/67 genomes from Rio de Janeiro) and mid-2017 (clade RJ2, n = 4/67). We detected evidence for positive selection in non-structural proteins linked with viral replication in the RJ1 clade (clade-defining: nsP4-A481D) and the RJ2 clade (nsP1-D531G). Finally, we estimate the CHIKV-ECSA's basic reproduction number (R0) to be between 1.2 to 1.6 and show that its instantaneous reproduction number (Rt) displays a strong seasonal pattern with peaks in transmission coinciding with periods of high Aedes aegypti transmission potential. Our results highlight the need for continued genomic and epidemiological surveillance of CHIKV in Brazil, particularly during periods of high ecological suitability, and show that selective pressures underline the emergence and evolution of the large urban CHIKV-ECSA outbreak in Rio de Janeiro

Kinetics and 28-day test-retest repeatability and reproducibility of [C-11]UCB-J PET brain imaging

[C-11]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test-retest repeatability (TRT) of quantitative [C-11]UCB-J brain positron emission tomography (PET) imaging in Alzheimer's disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [C-11]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K-1) and volume of distribution (V-T) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_V-B and 2T4k_V-B described the [C-11]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for V-T, DVR and SRTM BPND were -2.2% +/- 8.5, 0.4% +/- 12.0 and -8.0% +/- 10.2, averaged over all subjects. [C-11]UCB-J kinetics can be well described by a 1T2k_V-B model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for V-T, DVR and BPND wa

Inhibition of IL-10 Production by Maternal Antibodies against Group B Streptococcus GAPDH Confers Immunity to Offspring by Favoring Neutrophil Recruitment

Group B Streptococcus (GBS) is the leading cause of neonatal pneumonia, septicemia, and meningitis. We have previously shown that in adult mice GBS glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extracellular virulence factor that induces production of the immunosuppressive cytokine interleukin-10 (IL-10) by the host early upon bacterial infection. Here, we investigate whether immunity to neonatal GBS infection could be achieved through maternal vaccination against bacterial GAPDH. Female BALB/c mice were immunized with rGAPDH and the progeny was infected with a lethal inoculum of GBS strains. Neonatal mice born from mothers immunized with rGAPDH were protected against infection with GBS strains, including the ST-17 highly virulent clone. A similar protective effect was observed in newborns passively immunized with anti-rGAPDH IgG antibodies, or F(ab')2 fragments, indicating that protection achieved with rGAPDH vaccination is independent of opsonophagocytic killing of bacteria. Protection against lethal GBS infection through rGAPDH maternal vaccination was due to neutralization of IL-10 production soon after infection. Consequently, IL-10 deficient (IL-10−/−) mice pups were as resistant to GBS infection as pups born from vaccinated mothers. We observed that protection was correlated with increased neutrophil trafficking to infected organs. Thus, anti-rGAPDH or anti-IL-10R treatment of mice pups before GBS infection resulted in increased neutrophil numbers and lower bacterial load in infected organs, as compared to newborn mice treated with the respective control antibodies. We showed that mothers immunized with rGAPDH produce neutralizing antibodies that are sufficient to decrease IL-10 production and induce neutrophil recruitment into infected tissues in newborn mice. These results uncover a novel mechanism for GBS virulence in a neonatal host that could be neutralized by vaccination or immunotherapy. As GBS GAPDH is a structurally conserved enzyme that is metabolically essential for bacterial growth in media containing glucose as the sole carbon source (i.e., the blood), this protein constitutes a powerful candidate for the development of a human vaccine against this pathogen

Comportamentos agressivos em crianças e adolescentes com risco para esquizofrenia: diferenças entre gêneros

OBJECTIVE: This study aimed to investigate whether differences in aggression-related behavioral problems occur between boys and girls at high risk for schizophrenia living in the city of São Paulo, Brazil. METHOD: Using the Child Behavior Checklist, we compared the prevalence of behavioral problems between genders for the offspring (6-18 years) of mothers with diagnosis of schizophrenia and a comparison group of children born to women with no severe mental disorders recruited at the gynecology outpatient clinic of the same hospital. The Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition was applied for the evaluation of diagnostic status of mothers. RESULTS: Male children of women with schizophrenia had a lower prevalence of aggressive behavior compared to females (4% vs. 36%; p = 0.005), whereas no gender differences regarding aggression were detected in the comparison group (24% vs. 32%; p = 0.53). Logistic regression analyses showed that male gender and being a child of women with schizophrenia interacted so as to favor lower prevalence of aggressive behavior (p = 0.03). CONCLUSION: These findings reinforce the notion that behavioral gender differences related to schizophrenia are already detectable in childhood.OBJETIVO: Investigar diferenças da ocorrência de comportamentos agressivos entre crianças e adolescentes do sexo masculino e feminino com risco genético para desenvolver esquizofrenia. MÉTODO: A prevalência de comportamentos agressivos foi medida utilizando o inventário de comportamentos para crianças e adolescentes, Child Behavior Checklist, e comparada entre os gêneros para o grupo de crianças filhas de mulheres com esquizofrenia e para um grupo de crianças filhas de mulheres atendidas no serviço de ginecologia do mesmo hospital. A entrevista clínica estruturada para DSM-IV (The Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition) foi utilizada para confirmar o diagnóstico materno. RESULTADOS: Os filhos de mulheres com esquizofrenia do sexo masculino apresentaram prevalência menor de comportamentos agressivos quando comparados às meninas (4% x 36%; p = 0,005), o que não ocorreu para o grupo comparativo (24% x 32%; p = 0,53). A análise de regressão logística mostrou que pertencer ao sexo masculino e ser filho de mulher com esquizofrenia interagiram de forma a favorecer menor prevalência de comportamentos agressivos (p = 0,03). CONCLUSÃO: Esses achados corroboram para a noção que as diferenças comportamentais entre os gêneros na esquizofrenia podem ser detectadas precocemente durante a infância