The early evolution of COVID-19 incidence and mortality among people aged under 80 years or 80 years and above after COVID-19 vaccine implementation in the state of Bahia, Brazil.

This study evaluates the early effects of COVID-19 vaccine implementation in the number of cases and deaths due to COVID-19 among those aged < 80 years or ≥ 80 years in the state of Bahia, Brazil. For that, we used data from the Bahia state Secretary of Health platform of cases and deaths due to COVID-19 in all age groups, between March 2020 and May 2021, when 82% of COVID-19 vaccines were CoronaVac. Overall, there were 1,012,200 cases and 21,241 deaths due to COVID-19, of which, respectively, 2.3% and 25.3% occurred in patients aged ≥ 80 years. The median proportion of deaths in those ≥ 80 years decreased from 29.8% (27.8%-30.4%) in the pre- to 18.8% (15.6%-18.8%) in the post-vaccine periods (p = 0.04). Significant reduction in the median proportion of deaths from COVID-19 among those aged ≥ 80 years after COVID-19 vaccine implementation was found, which suggests CoronaVac effectiveness against death from COVID-19 in the elderly.

Cell adhesion proteins in the cerebrospinal fluid of neonates prenatally exposed to Zika virus: A case-control study.

To compare cell adhesion molecules levels in cerebrospinal fluid (CSF) between Zika virus (ZIKV)-exposed neonates with/without microcephaly (cases) and controls, 16 neonates (cases), 8 (50%) with and 8 (50%) without microcephaly, who underwent lumbar puncture (LP) during the ZIKV epidemic (2015-2016) were included. All mothers reported ZIKV clinical symptoms during gestation, all neonates presented with congenital infection findings, and other congenital infections were ruled out. Fourteen control neonates underwent LP in the same laboratory (2017-2018). Five cell adhesion proteins were measured in the CSF using mass spectrometry. Neurexin-1 (3.50 [2.00-4.00] vs. 7.5 [5.00-10.25], P = 0.001), neurexin-3 (0.00 [0.00-0.00] vs. 3.00 [1.50-4.00], P = 0.001) and neural cell adhesion molecule 2 (NCAM2) (0.00 [0.00-0.75] vs. 1.00 [1.00-2.00], P = 0.001) were significantly lower in microcephalic and non-microcephalic cases than in controls. When these two sub-groups of prenatally ZIKA-exposed children were compared to controls separately, the same results were found. When cases with and without microcephaly were compared, no difference was found. Neurexin-3 (18.8% vs. 78.6%, P = 0.001) and NCAM2 (25.0% vs. 85.7%, P = 0.001) were less frequently found among the cases. A positive correlation was found between cephalic perimeter and levels of these two proteins. Neurexin-2 and neurexin-2b presented no significant differences. Levels of three cell adhesion proteins were significantly lower in CSF of neonates exposed to ZIKV before birth than in controls, irrespective of presence of congenital microcephaly. Moreover, the smaller the cephalic perimeter, the lower CSF cell adhesion protein levels. These findings suggest that low CSF levels of neurexin-1, neurexin-3 and NCAM2 may reflect the effects of ZIKV on foetal brain development.

Impact of meningococcal C conjugate vaccine on incidence of invasive meningococcal disease in an 18-year time series in Brazil and in distinct Brazilian regions.

OBJECTIVE: To evaluate the impact of meningococcal C conjugate (MCC) vaccine in Brazil. METHODS: Ecological study assessing all invasive meningococcal disease (IMD) and meningococcal C disease (MenC) cases reported in all age groups, from 2001 to 2019. MCC was implemented in 2010. Data were collected on the DATASUS platform. Joinpoint regression was performed to assess the annual percent change (APC) of the incidence rate. RESULTS: Invasive meningococcal disease incidence decreased in all Brazilian regions from 2001 onwards, without apparent additional reduction attributable to MCC vaccine in the North, Northeast and South. The higher and statistically significant APC reduction in all age groups, in the North and South, and in children <5 years, in the Northeast, occurred between 2001 and 2011 (-15.4%), 2004 and 2012 (-14.4%), and 2001 and 2013 (-10.3%), respectively, before MCC vaccine implementation. Annual incidence of MenC in children under 5 years significantly fell in the North (-6.8%; 2011-2018), Southeast (-40.6%; 2010-2015) and Midwest (-48.6%; 2010-2014), which may be attributable to MCC implementation. CONCLUSION: Invasive meningococcal disease and MenC behaved differently after MCC vaccine implementation in Brazil during this 18-year time-series analysis. This suggests that the control of IMD should be based on multiple public health care measures and considered on a regional basis.

Delafloxacin as a treatment option for community-acquired pneumonia infection.

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in adults. Bacterial pathogens are recognized to be frequent causative agents, which makes antibacterial treatment crucial for the evolution of these patients. There are several antimicrobial options available in daily practice. However, bacterial resistance is a problem. The chemical, pharmacokinetic, pharmacodynamics, and safety characteristics of delafloxacin, a fluoroquinolone, are discussed. The data from one phase 3 clinical trial evaluating the use of delafloxacin in adults with community-acquired pneumonia is also discussed, along with findings from other meaningful studies. In vitro data have shown that delafloxacin has broad spectrum activity. Results from phase 2 and phase 3 studies have demonstrated that delafloxacin use is safe. International guidelines have recommended respiratory fluoroquinolones as second option for non-severe cases and must be considered in very severe patients not improving to a betalactam/macrolide combination. Delafloxacin was compared to moxifloxacin in the phase 3 community-acquired pneumonia trial. Serious and life-long adverse events due to fluoroquinolones use have been recently reported. Delafloxacin may possibly replace currently available fluoroquinolones, particularly in the treatment of resistant pathogens, such as ciprofloxacin-resistant P. aeruginosa isolates when other drugs are inefficient.

Differences between children with severe acute lower respiratory infection with or without SARS-Cov-2 infection.

AIM: to compare clinical features and outcome of children with severe acute lower respiratory infection (ALRI) with or without SARS-CoV-2 infection admitted to Paediatric Intensive Care Unit (PICU). METHODS: for this retrospective cohort study, all children aged<17 years admitted with severe ALRI at a PICU, in Salvador, Brazil were evaluated. Investigation of SARS-CoV-2 infection was performed by real-time reverse-transcription PCR. Clinical data, physical findings upon admission and outcome were registered. Patients were categorized by with or without SARS-Cov-2 infection. Outcomes were death and invasive mechanical ventilation (IMV). RESULTS: we enrolled 210 patients, whose median age was 2.8 years (IQR: 7.1 months-6.2 years). IMV was used in 33 (15.7%; 95%CI 11.3%-21.1%) patients. Eight (3.8%; 95%CI 1.8%-7.1%) cases died. 62 patients (29.5%) tested positive for SARS-CoV-2. Male gender (67.7% vs. 52.7%, P = 0.045) and sickle cell disease (6.5% vs. 0%, P = 0.007) were associated with SARS-CoV-2 infection. Wheezing upon admission was more common in patients without SARS-CoV-2 infection (38.5% vs. 21.0%, P = 0.01). IMV was more frequent among patients with SARS-CoV-2 infection (25.8% vs. 11.5%, P = 0.009) as well as death (8.1% vs. 2.0%, P = 0.05). CONCLUSION: children with severe ALRI infection with SARS-CoV-2 need IMV more frequently than those without it.

Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid.

Not every neonate with congenital Zika virus (ZIKV) infection (CZI) is born with microcephaly. We compared inflammation mediators in CSF (cerebrospinal fluid obtained from lumbar puncture) between ZIKV-exposed neonates with/without microcephaly (cases) and controls. In Brazil, in the same laboratory, we identified 14 ZIKV-exposed neonates during the ZIKV epidemic (2015-2016), 7(50%) with and 7(50%) without microcephaly, without any other congenital infection, and 14 neonates (2017-2018) eligible to be controls and to match cases. 29 inflammation mediators were measured using Luminex immunoassay and multidimensional analyses were employed. Neonates with ZIKV-associated microcephaly presented substantially higher degree of inflammatory perturbation, associated with uncoupled inflammatory response and decreased correlations between concentrations of inflammatory biomarkers. The groups of microcephalic and non-microcephalic ZIKV-exposed neonates were distinguished from the control group (area under curve [AUC] = 1; P < 0.0001). Between controls and those non-microcephalic exposed to ZIKV, IL-1ß, IL-3, IL-4, IL-7 and EOTAXIN were the top CSF markers. By comparing the microcephalic cases with controls, the top discriminant scores were for IL-1ß, IL-3, EOTAXIN and IL-12p70. The degree of inflammatory imbalance may be associated with microcephaly in CZI and it may aid additional investigations in experimental pre-clinical models testing immune modulators in preventing extensive damage of the Central Nervous System.

Seasonality of distinct respiratory viruses in a tropical city: implications for prophylaxis.

OBJECTIVE: The frequency and seasonality of viruses in tropical regions are scarcely reported. We estimated the frequency of seven respiratory viruses and assessed seasonality of respiratory syncytial virus (RSV) and influenza viruses in a tropical city. METHODS: Children (age ≤ 18 years) with acute respiratory infection were investigated in Salvador, Brazil, between July 2014 and June 2017. Respiratory viruses were searched by direct immunofluorescence and real-time polymerase chain reaction for detection of RSV, influenza A virus, influenza B virus, adenovirus (ADV) and parainfluenza viruses (PIV) 1, 2 and 3. Seasonal distribution was evaluated by Prais-Winsten regression. Due to similar distribution, influenza A and influenza B viruses were grouped to analyse seasonality. RESULTS: The study group comprised 387 cases whose median (IQR) age was 26.4 (10.5-50.1) months. Respiratory viruses were detected in 106 (27.4%) cases. RSV (n = 76; 19.6%), influenza A virus (n = 11; 2.8%), influenza B virus (n = 7; 1.8%), ADV (n = 5; 1.3%), PIV 1 (n = 5; 1.3%), PIV 3 (n = 3; 0.8%) and PIV 2 (n = 1; 0.3%) were identified. Monthly count of RSV cases demonstrated seasonal distribution (b3 = 0.626; P = 0.003). More than half (42/76 [55.3%]) of all RSV cases were detected from April to June. Monthly count of influenza cases also showed seasonal distribution (b3 = -0.264; P = 0.032). Influenza cases peaked from November to January with 44.4% (8/18) of all influenza cases. CONCLUSIONS: RSV was the most frequently detected virus. RSV and influenza viruses showed seasonal distribution. These data may be useful to plan the best time to carry out prophylaxis and to increase the number of hospital beds.

The impact of 10-valent pneumococcal conjugate vaccine upon hospitalization rate of children with pneumonia in different Brazilian administrative regions.

BACKGROUND: Streptococcus pneumoniae is the most frequent bacterial causative agent of pneumonia. Due to its significant contribution to the morbidity and mortality profile and the country's economy, the 10-valent pneumococcal vaccine (PCV10) was introduced in Brazil in 2010. Brazil is divided into five administrative regions which differ in social-economic indices among each other. Estimates of PCV10 impact on hospitalization rates due to pneumonia stratified by distinct Brazilian regions are limited. We assessed this issue. METHODS: This is a population-based ecological investigation. Data about hospitalizations due to pneumonia, asthma or urinary tract infection (UTI) among patients aged under 20 years in the pre-exposure (2003-2009) and in the post-exposure (2011-2017) periods were retrieved from the National Health System - Hospital Information System (SIH-SUS) database. The total resident population by age group in each year was retrieved from the Brazilian Institute for Geography and Statistics database. Hospitalization rates were estimated for each Brazilian region and the rates obtained in the pre-exposure and in the post-exposure periods were compared by Prais-Winsten regression. The Human Development Index (HDI) evolved differently in the distinct regions during the study period. RESULTS: Overall, hospitalization rates due to pneumonia declined by 34.5%. Similar trends were observed for hospitalization rates due to asthma and UTI. The same pattern was observed in each Brazilian region. However, the North region was the only one that presented an exponential incidence decline pattern, which could be explained by PCV10 implementation (declined by 10.8% in the quadratic regression, p < 0.01). Only in the North region, significant decline was observed among patients aged 0-4 years (-12.5%; p = 0.01), 5-9 years (-38.5%; p < 0.01) or 10-14 years (-10.7%; p = 0.03). CONCLUSION: Significant variation in the downward trend of hospitalization rate was only found in the North region, which evolved from very low HDI in 2003; medium HDI in 2010 to high HDI in 2017.

Effect of pneumococcal conjugate vaccines on mortality from lower respiratory infections and pneumonia among under-fives.

There is a well-known inverse association between mortality rate from infectious diseases and improvements in socioeconomic status, even though longer time-series are required to demonstrate this relationship. This general rule seems to apply to mortality from pneumonia in children in the pneumococcal conjugate vaccine (PCV) era. Two recent published secular trend studies spanning from about 30 years among Brazilians under the age of five show either no effect of PCV - not even death rate decline from pneumococcal meningitis - or a modest one (8% reduction). Time-series mortality studies from pneumonia are needed for both, developed and developing countries, those who have implemented PCV or not. Results from these studies would provide critical input and feedback to public health policy makers.

Systemic cytokines/chemokines associated to radiographic abnormalities in pneumonia in children.

Community-acquired pneumonia (CAP) diagnosis remains a challenge in paediatrics. Chest radiography is considered gold standard for definition of pneumonia, however no previous study assessed the relationship between immune response and radiographic-confirmed-pneumonia. We assessed association between cytokines/chemokines levels and radiographic abnormalities in children with CAP. Children < 5-years-old hospitalized with CAP were investigated in a prospective study at the Federal University of Bahia Hospital, Brazil. On admission, clinical data and biological samples were collected to investigate 20 aetiological agents and determine serum cytokines/chemokines levels; chest radiographs were performed. Among 158 patients, radiographic diagnosis of pneumonia was confirmed in 126(79.7%) and 17(10.8%) had pleural effusion. Viral, bacterial and pneumococcal infection were detected in 80(50.6%), 78(49.4%) and 37(23.4%) cases. By comparing the median concentrations of serum cytokines/chemokines between children with or without pleural effusion, interleukin(IL)-6 was higher (26.6[18.6-103.7] vs 3.0[0.0-19.8]; p < 0.001) among those with pleural effusion; and between children with or without radiographic-confirmed-pneumonia, IL-6 was higher in the first subgroup (4.5[0.0-23.4] vs 0.0[0.0-3.6]; p = 0.02) after having excluded cases with pleural effusion. Stratified analyses according to aetiology showed IL-6 increase in the radiographic-confirmed-pneumonia subgroup inside the pneumococcal infection (28.2[5.9-64.1] vs 0.0[0.0-0.0]; p = 0.03) subgroup. By multivariable analysis, with IL-6 as dependent variable, pneumococcal infection and pleural effusion showed independent association with IL-6 elevation [respective OR: 5.071 (95%CI = 2.226-11.548; p < 0.001) and 13.604 (95%CI = 3.463-53.449; p = 0.0001)]. Considering the cases without pleural effusion, the area under the curve of IL-6 to predict pneumococcal infection was 0.76 (95%CI = 0.66-0.86; p < 0.001). IL-6 increase is a potential biomarker of pneumococcal infection among children with CAP without pleural effusion upon admission.

Recurrent wheezing, allergic rhinitis, and maternal asthma as predictors of asthma in children.

Background: Early prediction of asthma is crucial for asthma prevention. Objective: We estimated the odds ratio (OR) of recurrent wheezing during the first 3 years of life, atopic rhinitis, and maternal asthma for asthma in school-age children (ages ≥ 6 years). Methods: This case-control study was conducted in Salvador, Brazil. Medical records of children diagnosed with asthma (cases) and of children screened for pulmonary illnesses and without asthma (controls) were reviewed. Information was retrieved and registered in standardized forms. Results: We included 125 subjects (cases) and 375 controls, whose median (percentile 25th-percentile 75th) age was 8.1 years (6.6-10.0 years) and 9.2 years (7.0-11.9 years), respectively. The subjects (cases) and the controls had at least three episodes of wheezing during the first 3 years of life (69.7% and 1.4%, respectively), a maternal history of asthma (36.0% and 4.0%, respectively), and atopic rhinitis (95.9% and 35.1%, respectively). The adjusted OR of three or more episodes of wheezing during the first 3 years of life was OR 132.5 (95% confidence interval [CI], 36.8-477.1), of a personal history of atopic rhinitis was OR 21.3 (95% CI, 5.3-85.0), and of maternal asthma was OR 10.2 (95% CI, 3.1-33.6) for asthma in a logistic regression (which also included age, gender, and maternal history of allergic rhinitis [OR insignificant for these factors]). Conclusion: Children with a history of three or more episodes of wheezing during the first 3 years of life were at least 37 times more likely to develop asthma than children without this history. A maternal history of asthma and a personal history of atopic rhinitis are also predictors of asthma in children.

The Negative Predictive Ability of Immature Neutrophils for Bacteremia in Children With Community-Acquired Infections.

Background: Bacteremia is a serious condition. We aimed to assess the role of immature neutrophils in peripheral blood smears for prediction of bacteremia in children. Methods: In this cross-sectional study conducted in Salvador, Brazil, blood cultures collected from patients aged ≤18 years were identified. White Blood Cell count (WBC) was performed upon admission. Medical charts were reviewed and cases from the community were included. Results: Out of 833 potentially eligible patients, 263 (31.6%) were excluded. Therefore, the study group comprised 570 patients being blood collected for culture upon admission from all of them and WBC performed upon admission from 566. The median age was 2 years (IQR: 9.4 mo-5 y) and 300 (52.6%) were male. Acute respiratory infection was the most frequent diagnosis (n = 388; 68.1%), being 250 (43.9%) lower (LRTI) and 138 (24.2%) upper respiratory tract infections. Blood culture was positive in 9 (1.6%; 95% CI: 0.8-2.9%) cases, out of which 7 (2.8%) had LRTI. Streptococcus pneumoniae (n = 3), Haemophilus (n = 2), Neisseria meningitidis, viridans streptococci, Streptococcus agalactiae, and Acinetobacter baumanii (n = 1 each) were isolated. The total WBC/mm3 did not differ when children with positive or negative blood culture were compared (12,100 [IQR: 6,950-15,250] vs. 11,000 [IQR: 7,900-14,900]; P = 0.9). However, presence of any immature neutrophil was significantly more frequent among patients with bacteremia in comparison with patients without bacteremia (100% [9/9] vs. 40% [223/557]; P < 0.001). The absolute number of immature neutrophils was significantly lower among children without bacteremia (0 [IQR: 0-259] vs. 325 [IQR: 275-1,106]; P < 0.001). Overall, the area under the ROC curve of the number of immature neutrophils in regard to bacteremia was 0.82 (95% CI: 0.76-0.88; P = 0.001). Among 413 patients with absolute number of immature neutrophils <242/mm3, none had bacteremia; among 153 patients with absolute number of immature neutrophils ≥242/mm3, 9 (5.9%) had bacteremia. Absolute number of immature neutrophils ≥242/mm3 showed: sensitivity 100% (95% CI: 71.7-100%), specificity 74.1% (95% CI: 70.4-77.7%), negative predictive value 100% (95% CI: 99.3-100.0%), and positive predictive value 5.9% (95% CI: 2.9-10.5%). When only children with LRTI were analyzed, the results were similar. Conclusion: The absolute number of immature neutrophils in peripheral blood smear is a potential tool to rule out bacteremia among children with community-acquired infections.

Community-acquired pneumonia among children: the latest evidence for an updated management / Pneumonia adquirida na comunidade em crianc¸as: as evidências mais recentes para um manejo atualizado

Abstract Objective To provide cutting-edge information for the management of community-acquired pneumonia in children under 5 years, based on the latest evidence published in the literature. Data source A comprehensive search was conducted in PubMed, by using the expressions: "community-acquired pneumonia" AND "child" AND "etiology" OR "diagnosis" OR "severity" OR "antibiotic". All articles retrieved had the title and the abstract read, when the papers reporting the latest evidence on each subject were identified and downloaded for complete reading. Data synthesis In the era of largely implemented bacterial conjugate vaccines and widespread use of amplification nucleic acid techniques, respiratory viruses have been identified as the most frequent causative agents of community-acquired pneumonia in patients under 5 years. Hypoxemia (oxygen saturation ≤96%) and increased work of breathing are signs most associated with community-acquired pneumonia. Wheezing detected on physical examination independently predicts viral infection and the negative predictive value (95% confidence interval) of normal chest X-ray and serum procalcitonin <0.25 ng/dL was 92% (77-98%) and 93% (90-99%), respectively. Inability to drink/feed, vomiting everything, convulsions, lower chest indrawing, central cyanosis, lethargy, nasal flaring, grunting, head nodding, and oxygen saturation <90% are predictors of death and can be used as indicators for hospitalization. Moderate/large pleural effusions and multilobar infiltrates are predictors of severe disease. Orally administered amoxicillin is the first line outpatient treatment, while ampicillin, aqueous penicillin G, or amoxicillin (initiated initially by intravenous route) are the first line options to treat inpatients. Conclusions Distinct aspects of childhood community-acquired pneumonia have changed during the last three decades.

Resumo Objetivo Fornecer informações de ponta para o manejo de crianças menores de cinco anos com pneumonia adquirida na comunidade, com base nas evidências mais recentes publicadas na literatura. Fonte de dados Uma pesquisa abrangente foi feita no PubMed, com as expressões: "community-acquired pneumonia" + "child" + "etiology" ou "diagnosis" ou "severity" ou "antibiotic". Todos os artigos encontrados tiveram o título e o resumo lidos e os artigos que relatavam as evidências mais recentes sobre cada assunto foram identificados e recuperados para leitura completa. Síntese dos dados Na era das vacinas bacterianas conjugadas amplamente usadas e do uso difundido de técnicas de amplificação de ácidos nucléicos, os vírus respiratórios foram identificados como os agentes causadores mais frequentes de pneumonia adquirida na comunidade em pacientes com menos de cinco anos. A hipoxemia (saturação de oxigênio ≤ 96%) e o aumento do esforço respiratório são os sinais mais associados à pneumonia adquirida na comunidade. A sibilância detectada ao exame físico prediz de forma independente a infecção viral e o valor preditivo negativo (intervalo de confiança de 95%) da radiografia de tórax normal e a procalcitonina sérica < 0,25 ng/dL foi de 92% (77-98%) e 93% (90-99%), respectivamente. Incapacidade de beber e se alimentar, vomitar todo o alimento, convulsões, retração torácica subcostal, cianose central, letargia, aleteo nasal, estridor e saturação de oxigênio < 90% são preditores de óbito e podem ser usados como indicadores de hospitalização. Derrames pleurais moderados/grandes e infiltrados multilobulares são preditores de doença grave. A amoxicilina administrada por via oral é a opção de primeira linha para tratar pacientes ambulatoriais e a ampicilina ou penicilina cristalina G ou amoxicilina (administrada inicialmente por via intravenosa) são as opções de primeira linha para tratar pacientes hospitalizados. Conclusões Aspectos distintos da pneumonia adquirida na comunidade durante a infância mudaram durante as últimas três décadas.

Lower respiratory infections mortality among Brazilians under-five before and after national pneumococcal conjugate vaccine implementation.

BACKGROUND: Studies on the impact of pneumococcal conjugate vaccines (PCV) on mortality, especially among preschoolers are scarce. We aimed to assess time trend mortality from lower respiratory infections (LRI), taken as a proxy of pneumonia, from 1990 to 2017. METHODS: This ecological study assessed the mortality rate among Brazilians under-five before and after the national PCV-10 implementation in 2010. Pneumococcal meningitis (PM) and diarrheal diseases (DD) were included as a "positive and negative controls", respectively. Trend analysis was performed through Global Burden of Disease estimates. Joinpoint regression modeling was used to describe trends in mortality and to identify time points of its statistically significant decreases throughout the study period. RESULTS: There was a sustainable reduction in mortality rates for these three diseases, with no relevant changes in the secular trends for LRI and PM after the PCV-10 implementation. For LRI, PM, and DD the higher and statistically significant (p < 0.05) annual percent change reduction occurred between 2000 and 2003, (-8.3%), 1997-2000 (-11.9%), and 1990-1994. (-13.8%), respectively, i.e., several years before the nationwide implementation of PCV-10. Moreover, for LRI the annual percent change (from -5.9 to -8.8) verified from 1990 to 2009, i.e., 20 years before countrywide vaccination, was comparable to that observed during the PCV era, that is, from minus 5.8 to minus 7.8, between 2010 and 2017. CONCLUSION: Mortality from LRI, PM, and DD decreased over time, irrespective of national PCV-10 implementation in Brazil. Other factors such as healthcare delivery, socioeconomic status improvement, and health interventions may have impacted this secular trend.

Cerebrospinal fluid immunoglobulins are increased in neonates exposed to Zika virus during foetal life.

OBJECTIVE: To compare immunoglobulin levels in cerebrospinal fluid (CSF) of neonates exposed to Zika virus (ZIKV) during foetal life (cases) with levels in CSF of control neonates. METHODS: We identified 16 neonates who underwent lumbar puncture (LP), during the ZIKV epidemic (December/2015 to March/2016) whose mothers reported ZIKV clinical symptoms during gestation (cases). Congenital microcephaly was defined as head circumference ≤31.9 cm (boys) and ≤31.5 cm (girls) for term neonates, or ≤2 standard deviations below the mean for premature (<37 weeks) neonates. Subsequently, we identified neonates who underwent LP in the same lab and fulfilled criteria to be controls: age ≤4 days, CSF white blood cell count ≤8/mm3, CSF protein ≤132 mg/dL, CSF red blood cell count ≤1,000/mm3, neither central nervous system illness, nor congenital infection, nor microcephaly. CSF immunoglobulin concentrations were measured by mass spectrometry. RESULTS: 13 controls were included. IgM, IgA, IgG, IgK, and IgL were significantly higher among cases (p < 0.001). Eight (50%) ZIKV exposed infants had congenital microcephaly. These showed the strongest immunoglobulin elevation of the IgM and IgA classes. CONCLUSION: Neonates exposed to ZIKV infection during gestation present with elevated distinct immunoglobulins in CSF, both in cases that developed microcephaly and in cases that did not.

Evolution of cytokines/chemokines in cases with community-acquired pneumonia and distinct etiologies.

AIM: To compare the systemic cytokines/chemokines levels over time during the evolution of children hospitalized with community-acquired pneumonia (CAP) with and without pneumococcal infection. METHODS: Children less than 5-years-old hospitalized with CAP were prospectively investigated in Salvador, Brazil. Clinical data and biological samples were collected to investigate 20 etiological agents and to determine serum cytokines/chemokines levels on admission and 2 to 4 weeks later. Cases with pneumococcal infection received this diagnosis irrespective of also having other etiologies. RESULTS: A total of 277 patients were enrolled, however, serum sample was unavailable for cytokine measurement upon admission (n = 61) or upon follow-up visit (n = 36), etiology was undetected (n = 50) and one patient did not attend the follow-up visit. Therefore, this study group comprised of 129 cases with established etiology. The median (interquartile range) age and sampling interval was 18 (9-27) months and 18 (16-21) days, respectively. Established etiology was viral (52.0%), viral-bacterial (30.2%), and bacterial (17.8%). Pneumococcal infection was found in 31 (24.0%) patients. Overall, median interleukin-6 (IL-6; 10.6 [4.7-30.6] vs 21.0 [20.2-21.7]; P = .03), IL-10 (3.5 [3.1-4.5] vs 20.1 [19.8-20.4]; P < .001), and CCL2 (19.3 [12.4-23.2] vs 94.0 [67.2-117.8]; P < .001) were significantly higher in convalescent serum samples, whereas median CXCL10 (83.6 [36.4-182.9] vs 14.6 [0-116.6]; P < .001) was lower. Acute vs convalescent levels evolution of IL-10, CCL2, and CXCL10 did not differ among patients with or without pneumococcal infection. However, IL-6 decreased (27.8 [12.3-48.6] vs 20.8 [20.2-22.6]; P = .1) in patients with pneumococcal infection and increased (9.0 [4.2-22.6] vs 21.0 [20.2-21.7]; P = .001) in patients without it. CONCLUSION: The marked increase of IL-6 serum levels during the acute phase makes it a potential biomarker of pneumococcal infection among children with CAP.

Community-acquired pneumonia among children: the latest evidence for an updated management.

OBJECTIVE: To provide cutting-edge information for the management of community-acquired pneumonia in children under 5 years, based on the latest evidence published in the literature. DATA SOURCE: A comprehensive search was conducted in PubMed, by using the expressions: "community-acquired pneumonia" AND "child" AND "etiology" OR "diagnosis" OR "severity" OR "antibiotic". All articles retrieved had the title and the abstract read, when the papers reporting the latest evidence on each subject were identified and downloaded for complete reading. DATA SYNTHESIS: In the era of largely implemented bacterial conjugate vaccines and widespread use of amplification nucleic acid techniques, respiratory viruses have been identified as the most frequent causative agents of community-acquired pneumonia in patients under 5 years. Hypoxemia (oxygen saturation ≤96%) and increased work of breathing are signs most associated with community-acquired pneumonia. Wheezing detected on physical examination independently predicts viral infection and the negative predictive value (95% confidence interval) of normal chest X-ray and serum procalcitonin <0.25ng/dL was 92% (77-98%) and 93% (90-99%), respectively. Inability to drink/feed, vomiting everything, convulsions, lower chest indrawing, central cyanosis, lethargy, nasal flaring, grunting, head nodding, and oxygen saturation <90% are predictors of death and can be used as indicators for hospitalization. Moderate/large pleural effusions and multilobar infiltrates are predictors of severe disease. Orally administered amoxicillin is the first line outpatient treatment, while ampicillin, aqueous penicillin G, or amoxicillin (initiated initially by intravenous route) are the first line options to treat inpatients. CONCLUSIONS: Distinct aspects of childhood community-acquired pneumonia have changed during the last three decades.

Early Gross Motor Development Among Brazilian Children with Microcephaly Born Right After Zika Virus Infection Outbreak.

OBJECTIVE: To assess the gross motor development of children with presumed congenital Zika virus (ZIKV) infection over the first 2 years of their lives. METHODS: Seventy-seven children were assessed at the median ages of 11, 18, and 24 months, using the evaluative instrument Gross Motor Function Measure (GMFM-66). At the third assessment, the children with diagnoses of cerebral palsy (CP) were classified by severity through the Gross Motor Function Classification System (GMFCS) and stratified by topography indicating the predominantly affected limbs. With these instruments in combination and using the motor development curves as reference, the rate of development and functional ability were estimated. RESULTS: At 2 years of age, all children had the diagnosis of CP. Seventy-four (96.1%) presented gross motor skills similar to those of children aged 4 months or younger, according to the World Health Organization's standard. The GMFM-66 median score among the 73 (94.8%) children with quadriplegia and GMFCS level V showed significant change between 11 and 18 months (p < 0.001) and between 11 and 24 months (p < 0.001). No significant difference (p = 0.076) was found between 18 and 24 months. CONCLUSION: Despite showing some gross motor progress during the initial 18 months of life, these children with presumed congenital ZIKV infection and CP experienced severe motor impairment by 2 years of age. According to the motor development curves, these children with quadriplegia have probably already reached about 90% of their motor development potential.