Assessment and Prognostic Resources for Gross Motor Development in a Child with Cerebral Palsy Related to Congenital Zika Syndrome.

This article describes how the Gross Motor Ability Estimator (GMAE) software can provide important information based on the Gross Motor Function Measure (GMFM)-66 score of a child with congenital Zika syndrome.A child was assessed at 9, 17, and 25 months of age through the GMFM-66. At 2 years, the child's gross motor ability was estimated and classified according to the Gross Motor Function Classification System (GMFCS).At 2 years of age, the child in this case required assistance to roll and was unable to maintain antigravity trunk posture in sitting position, typical abilities of GMFCS level V.GMAE can be useful to guide health professionals that care for children with lifelong physical and developmental care needs. This is the first study that demonstrated how to use the GMAE in this specific population.

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.

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.

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.

Systemic cytokines and chemokines on admission of children hospitalized with community-acquired pneumonia.

Community-acquired pneumonia (CAP) is the main cause of death in children under-5 years worldwide and Streptococcus pneumoniae is the most common bacterial agent. However, it is difficult to identify pneumococcal infection among children with CAP. We aimed to assess association between any cytokine/chemokine and pneumococcal infection in childhood CAP. Furthermore, we evaluated the diagnostic value of cytokine/chemokine for pneumococcal infection. This prospective study was conducted at an Emergency Room, in Salvador, Brazil. Children <5-years-old hospitalized with CAP in a 21-month period were evaluated. On admission, clinical and radiological data were collected along with biological samples to investigate 20 etiological agents and determine serum cytokines (interleukin (IL)-8, IL-6, IL-10, IL-1ß, IL-12, TNF-α, IL-2, IL-4, IL-5, γ-interferon), and chemokines (CCL2, CCL5, CXCL9, CXCL10) concentration. From 166 patients with etiology detected, pneumococcal infection was detected in 38 (22.9%) cases among which the median IL-6(pg/ml) was 31.2 (IQR: 12.4-54.1). The other 128 cases had other causative agents detected (Haemophilus influenzae, Moraxella catarrhalis, atypical bacteria and viruses) with the median IL-6 concentration being 9.0 (IQR: 4.1-22.0; p < 0.001). The area under the ROC curve for IL-6 to predict pneumococcal CAP was 0.74 (95%CI: 0.65-0.83; p < 0.001). By multivariate analysis, with pneumococcal CAP as dependent variable, IL-6 was an independent predictor for pneumococcal infection (OR = 5.56; 95%CI: 2.42-12.75, cut-off point = 12.5 pg/ml; p = 0.0001). The negative predictive value of IL-6 under 12.5 pg/ml for pneumococcal infection was 90% (95%CI: 82-95%). Independently significant difference was not found for any other cytokines/chemokines. Serum IL-6 concentration on admission is independently associated with pneumococcal infection among children under-5 years hospitalized with CAP.

Evolution of acute infection with atypical bacteria in a prospective cohort of children with community-acquired pneumonia receiving amoxicillin.

Background: Atypical bacteria are treatable causative agents of community-acquired pneumonia (CAP). However, there is no conclusive evidence that a child with CAP should receive empirical treatment against such agents. Objectives: We assessed the possibility of association between clinical failure and acute infection by these bacteria among children with CAP treated with amoxicillin. Patients and methods: Patients aged 2-59 months with non-severe CAP received amoxicillin during prospective follow-up. Acute and convalescent blood samples were collected. Probable acute infection by Mycoplasma pneumoniae (specific IgM antibodies), by Chlamydia pneumoniae or Chlamydia trachomatis (specific IgM antibodies and/or IgG/IgA titre change) was investigated. Outcomes were assessed during follow-up at 2, 5 and 14-28 days. Treatment failure included development of danger signs, persistent fever, tachypnoea or death. ClinicalTrials.gov: NCT01200706. Results: Of 787 children, 86 (10.9%; 95% CI = 8.9%-13.3%) had acute M. pneumoniae infection. C. pneumoniae acute infection was found in 79 of 733 (10.8%; 95% CI = 8.7%-13.2%) and C. trachomatis was found in 3 of 28 (10.7%; 95% CI = 2.8%-26.5%) <6 months old. Among patients with or without treatment failure at 2 days, acute M. pneumoniae infection (11.7% versus 10.7%; P = 0.7), acute C. pneumoniae infection (8.5% versus 11.3%; P = 0.3) and acute C. trachomatis infection (16.7% versus 9.1%; P = 0.5) were found. No significant differences were found with regard to treatment failure at the 5 day evaluation. Overall, amoxicillin was substituted in 3.5% versus 2.7% among patients with or without acute infection by one of these bacteria ( P = 0.6). Conclusions: The overall substitution rate of amoxicillin was very low. It is not necessary to give an empirical non-ß-lactam antibiotic as a first-line option to treat every child between 2 and 59 months old with non-severe CAP.

Comparison of the frequency of bacterial and viral infections among children with community-acquired pneumonia hospitalized across distinct severity categories: a prospective cross-sectional study.

BACKGROUND: The comparison of the frequencies of bacterial and viral infections among children with community-acquired pneumonia (CAP) admitted in distinct severity categories, in an original study, is lacking in literature to-date. We aimed to achieve this goal. METHODS: Children aged 2-59-months-old hospitalized with CAP were included in this prospective study in Salvador, Brazil. Clinical data and biological samples were collected to investigate 11 viruses and 8 bacteria. Severity was assessed by using the World Health Organization criteria. RESULTS: One hundred eighty-one patients were classified as "non-severe" (n = 53; 29.3 %), "severe" (n = 111; 61.3 %), or "very severe" (n = 17; 9.4 %) CAP. Overall, aetiology was detected among 156 (86.2 %) cases; viral (n = 84; 46.4 %), bacterial (n = 26; 14.4 %) and viral-bacterial (n = 46; 25.4 %) infections were identified. Viral infection frequency was similar in severe/very severe and non-severe cases (46.1 % vs. 47.2 %; p = 0.9). Pneumococcal infection increased across "non-severe" (13.2 %), "severe" (23.4 %), and "very severe" (35.3 %) cases (qui-squared test for trend p = 0.04). Among patients with detected aetiology, after excluding cases with co-infection, the frequency of sole bacterial infection was different (p = 0.04) among the categories; non-severe (12.5 %), severe (29.3 %) or very severe (55.6 %). Among these patients, sole bacterial infection was independently associated with severity (OR = 4.4 [95 % CI:1.1-17.6]; p = 0.04) in a model controlled for age (OR = 0.7 [95 % CI:0.5-1.1]; p = 0.1). CONCLUSIONS: A substantial proportion of cases in distinct severity subgroups had respiratory viral infections, which did not differ between severity categories. Bacterial infection, particularly pneumococcal infection, was more likely among severe/very severe cases.

Differences upon admission and in hospital course of children hospitalized with community-acquired pneumonia with or without radiologically-confirmed pneumonia: a retrospective cohort study.

BACKGROUND: The use of chest radiograph (CXR) for the diagnosis of childhood community-acquired pneumonia (CAP) is controversial. We assessed if children with CAP diagnosed on clinical grounds, with or without radiologically-confirmed pneumonia on admission, evolved differently. METHODS: Children aged ≥ 2 months, hospitalized with CAP diagnosed on clinical grounds, treated with 200,000 IU/Kg/day of aqueous penicillin G for ≥ 48 h and with CXR taken upon admission, without pleural effusion, were included in this retrospective cohort. One researcher, blinded to the radiological diagnosis, collected data on demographics, clinical history and physical examination on admission, daily hospital course during the first 2 days of treatment, and outcome, all from medical charts. Radiological confirmation of pneumonia was based on presence of pulmonary infiltrate detected by a paediatric radiologist who was also blinded to clinical data. Variables were initially compared by bivariate analysis. Multi-variable logistic regression analysis assessed independent association between radiologically-confirmed pneumonia and factors which significantly differed during hospital course in the bivariate analysis. The multi-variable analysis was performed in a model adjusted for age and for the same factor present upon admission. RESULTS: 109 (38.5%) children had radiologically-confirmed pneumonia, 143 (50.5%) had normal CXR and 31 (11.0%) had atelectasis or peribronchial thickening. Children without radiologically-confirmed pneumonia were younger than those with radiologically-confirmed pneumonia (median [IQR]: 14 [7-28 months versus 21 [12-44] months; P = 0.001). None died. The subgroup with radiologically-confirmed pneumonia presented fever on D1 (33.7 vs. 19.1; P = 0.015) and on D2 (31.6% vs. 16.2%; P = 0.004) more frequently. The subgroup without radiologically-confirmed pneumonia had chest indrawing on D1 (22.4% vs. 11.9%; P = 0.027) more often detected. By multi-variable analysis, Fever on D2 (OR [95% CI]: 2.16 [1.15-4.06]) was directly and independently associated with radiologically-confirmed pneumonia upon admission. CONCLUSION: The compared subgroups evolved differently.

Retrospective analysis of the efficacies of two different regimens of aqueous penicillin G administered to children with pneumonia.

Community-acquired pneumonia (CAP) is an important childhood health problem. Penicillin remains appropriate for treating children with CAP. Clinical data are lacking on disease evolution in children treated with different posologic schemes of aqueous penicillin G. To assess if there were differences in disease evolution between children with CAP treated with 6 or 4 daily doses of aqueous penicillin G, we reviewed the medical charts of hospitalized patients 2 months to 11.5 years of age. Pneumonia was radiologically confirmed based on the detection of pulmonary infiltrate or pleural effusion on the chest radiograph taken on admission and read by a pediatric radiologist blinded to the clinical data. The total daily dose of aqueous penicillin G was 200,000 IU/kg of body weight. Data were recorded on admission, during disease evolution up to the 7th day of treatment, and at the final outcome. The results of hospitalization and the daily frequency of physical signs suggestive of pneumonia were assessed. The subgroups comprised 120 and 144 children who received aqueous penicillin G in 6 or 4 daily doses, respectively. Children≥5 years of age were more frequent in the 4-daily-doses subgroup (16.0% versus 4.2%; respectively, P=0.02). There were no differences between the compared subgroups in terms of final outcomes, lengths of hospitalization, durations of aqueous penicillin G use, frequencies of aqueous penicillin G substitution, or daily frequencies of tachypnea, fever, chest retraction, lower chest recession, nasal flaring, and cyanosis up to the 7th day of treatment. The studied posologic regimens were similarly effective in treating children hospitalized with a radiologically confirmed CAP diagnosis. Aqueous penicillin G (200,000 IU/kg/day) may be given in 4 daily doses to children with CAP.

Comparison of oral amoxicillin given thrice or twice daily to children between 2 and 59 months old with non-severe pneumonia: a randomized controlled trial.

OBJECTIVES: Oral amoxicillin (50 mg/kg/day) thrice daily is the first-line therapy for non-severe childhood pneumonia. Compliance could be enhanced if two daily doses are employed. We assessed the equivalence of oral amoxicillin (50 mg/kg/day) thrice or twice daily in those patients. PATIENTS AND METHODS: This randomized (1 : 1), controlled, triple-blinded investigation conducted at one centre in Brazil included children aged 2-59 months with non-severe pneumonia diagnosed by trained paediatricians based on respiratory complaints and radiographic pulmonary infiltrate/consolidation. Participants were randomly assigned to receive one bottle (Amoxicillin 1) at 6 am, 2 pm and 10 pm and the other bottle (Amoxicillin 2) at 8 am and 8 pm: one bottle contained amoxicillin and the other placebo and vice versa. Only the pharmacist knew patients' allocation. Follow-up assessments were done at 2, 5 and 14 days after enrolment. Chest radiographs were read by three independent radiologists. Primary outcome was treatment failure (development of danger signs, persistence of fever, tachypnoea, development of serious adverse reactions, death and withdrawal from the trial) at 48 h. ClinicalTrials.gov: identifier NCT01200706. RESULTS: Four hundred and twelve and 408 participants received amoxicillin thrice or twice daily, respectively. Treatment failure was detected in 94 (22.8%) and 94 (23.0%) patients in intention-to-treat analysis (risk difference 0.2%; 95% CI: -5.5%-6.0%) and in 80 (20.1%) and 85 (21.3%) patients in per-protocol analysis (risk difference 1.2%; 95% CI: -4.4%-6.8%). Pneumonia was radiologically confirmed by concordant reading in 277 (33.8%) cases, among whom treatment failure was registered in 25/133 (18.8%) and 27/144 (18.8%) participants from the thrice and twice daily doses subgroups, respectively (risk difference -0.05%; 95% CI: -9.3%-9.2%). CONCLUSIONS: Oral amoxicillin (50 mg/kg/day) twice daily is as efficacious as thrice daily.

Respiratory viral infections among children with community-acquired pneumonia and pleural effusion.

Pleural effusion (PE), a complication of community-acquired pneumonia (CAP), is usually attributed to a bacterial infection. Nonetheless, viral infections have not been investigated routinely. We searched for bacterial and viral infections among 277 children hospitalized with CAP. Among these children 206 (74%) had radiographic confirmation, of whom 25 (12%) had PE. The aetiology was established in 18 (72%) PE cases: bacterial (n = 5; 28%), viral (n = 9; 50%), and viral-bacterial (n = 4; 22%) infections were found. Infection by rhinovirus (n = 3), enterovirus, Streptococcus pneumoniae (n = 2 each), Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, influenza A virus, and respiratory syncytial virus (RSV) (n = 1 each) were detected as probable sole infections. Parainfluenza virus 1/3 + influenza A virus and RSV + influenza A virus (n = 1 each) were identified as mixed viral-viral infections. Probable viral non-bacterial infection was identified in a third of the cases with CAP and PE. It is advisable to investigate viral as well as bacterial infections among children with CAP and PE.

Human bocavirus infection diagnosed serologically among children admitted to hospital with community-acquired pneumonia in a tropical region.

Human bocavirus (HBoV) is a human virus associated with respiratory disease in children. Limited information is available on acute infection with HBoV among children admitted to hospital with community-acquired pneumonia in tropical regions and the current diagnosis is inadequate. The aims were to diagnose and describe acute HBoV infections among children hospitalized for community-acquired pneumonia. In Salvador, Brazil, 277 children with community-acquired pneumonia were prospectively enrolled. Paired serum samples were tested by IgG, IgM, and IgG-avidity enzyme immunoassays (EIAs) using recombinant HBoV VP2. HBoV DNA was detected in nasopharyngeal aspirates and serum by a quantitative polymerase-chain reaction (PCR). HBoV DNA was detected in nasopharyngeal aspirates of 62/268 (23%) children and 156/273 (57%) were seropositive. Acute primary HBoV infection was reliably diagnosed (bearing at least two acute markers: Positive IgM, a fourfold increase/conversion of IgG, low IgG avidity or viremia) in 21 (8%) of 273 patients, 90% of 20 had HBoV DNA in nasopharyngeal aspirates, 83% with a high DNA load. The median age of infection with HBoV was 16 months, range 5-36. Community-acquired pneumonia was confirmed radiographically in 85% of 20 patients with acute HBoV infection diagnosed serologically. HBoV DNA was found in nasopharyngeal aspirates of 42/246(17%) children without an acute primary HBoV infection and available nasopharyngeal aspirate. Four children with HBoV secondary immune responses were detected, lacking both IgM and viremia. HBoV infection was diagnosed accurately in children aged 5-36 months with community-acquired pneumonia confirmed radiographically. PCR of nasopharyngeal aspirates is not a reliable marker of acute HBoV infection.

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.

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.

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.

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.

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.