Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

SNPs, adipokynes and adiposity in children with asthma.

OBJECTIVES: Asthma and obesity are complex disorders influenced by environmental and genetic factors. We performed an integrative review of genetic polymorphisms and adipokines effects in children and adolescents with asthma and obesity. DATA SOURCES: Articles focused on these issues were collected from SciELO, PubMed, LILACS, Embase and ScienceDirect electronic databases, in 2009-2020 period. STUDY SELECTIONS: 22 articles were selected, including clinical trials, analyses approaches, case-control studies, meta-analysis and Mendelian randomization studies. RESULTS: Leptin concentrations were higher in obesity and asthma. The high value of BMI and Leptin indicated severe asthma. Adiponectin may be reduced in obese children. The high value of BMI and low level of Adiponectin may indicate severe asthma. Some linkage of PRKCA gene, asthma and BMI was observed. FTO T allele rs62048379 was positively associated with overweight/obesity, related to protein and PUFA:SFA ratio intake and influences the choice of more energy-dense foods. FTO rs9939609 effects are more pronounced among children with insufficient vitamin D levels. CONCLUSION: Leptin may be a potential predictor for asthma control in children. BMI and Adiponectin could have certain predictive value for asthma. FTO gene was related to a higher mean BMI Z-score and accelerated developmental age per allele. Strong genetic heterogeneity influencing on asthma and obesity susceptibilities is evident and related to distinct genetic features. GWAS with childhood obesity in asthma contributed to greater insights, mainly on later childhood. Standardized definitions for asthma and overweight/obesity in studies approaching adipokines and SNPs would provide stronger evidence in deciding the best management.

Contribution of Xpert MTB/RIF to clinical diagnosis in adolescents with tuberculosis in Rio de Janeiro, Brazil.

SETTING: Rio de Janeiro, RJ, Brazil, a high tuberculosis (TB) burden city.OBJECTIVE: To compare the sociodemographics, clinical characteristics, care process indicators (CPIs) and treatment outcomes among adolescents with pulmonary TB (PTB) and those with PTB + extrapulmonary TB (EPTB), who underwent testing with Xpert® and sputum culture.DESIGN: This was a retrospective study of data from three national databases from 2014 to 2016 of adolescents (aged 10-18 years) residing and notified in Rio de Janeiro City. Three groups were identified according to their Xpert and culture results: Group 1, Xpert- and culture-positive; Group 2, Xpert-positive and culture-negative; and Group 3, Xpert- and culture-negative. Study CPIs were as follows: the time between 'sample collection and Xpert result release', 'sample collection and treatment initiation' and 'notification and treatment outcome'.RESULTS: Of 258 adolescents included in the study, 223 (86.4%) were in Group 1, 20 (7.8%) in Group 2 and 15 (5.8%) in Group 3. Groups 1 and 2 had a similar profile. Compared to Group 1, Group 3 had a higher proportion of HIV-positive cases (21.4% vs. 3.0%, P = 0.016), adolescents with a hospital diagnosis (53.3% vs. 7.6%, P < 0.001), and PTB + EPTB cases (20% vs. 0.4%; P < 0.001). There were no statistically significant differences in CPIs or treatment outcomes.CONCLUSION: The clinical diagnosis was decisive in more critical or complex patients, despite Xpert-negative results.

Low light intensity and nitrogen starvation modulate the chlorophyll content of Scenedesmus dimorphus.

AIMS: Chlorophyll is a photosynthetic pigment found in plants and algal organisms and is a bioproduct with human health benefits and a great potential for use in the food industry. The chlorophyll content in microalgae strains varies in response to environmental factors. In this work, we assessed the effect of nitrogen depletion and low light intensity on the chlorophyll content of the Scenedesmus dimorphus microalga. METHODS AND RESULTS: The growth of S. dimorphus under low light intensity led to a reduction in cell growth and volume as well as increased cellular chlorophyll content. Nitrogen starvation led to a reduction in cell growth and the chlorophyll content, changes in the yield and productivity of chlorophylls a and b. Transmission electron microscopy was used to investigate the ultrastructural changes in the S. dimorphus exposed to nitrogen and light deficiency. CONCLUSIONS: In contrast to nitrogen depletion, low light availability was an effective mean for increasing the total chlorophyll content of green microalga S. dimorphus. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings acquired in this work are of great biotechnological importance to extend knowledge of choosing the right culture condition to stimulate the effectiveness of microalgae strains for chlorophyll production purposes.

Childhood tuberculosis and human immunodeficiency virus status in Brazil: a hierarchical analysis.

SETTING: Human immunodeficiency virus (HIV) infection may impact tuberculosis (TB) diagnosis, clinical presentation and treatment outcomes in children as the signs and symptoms of both diseases overlap. OBJECTIVE: To compare the sociodemographic and clinical profiles of childhood TB according to HIV status in Brazil. METHODS: This was a cross-sectional study of data on subjects aged <15 years retrieved from the Brazilian National Electronic Disease Registry (Sistema de Informação de Agravos de Notificação) database on TB to compare TB-HIV coinfected patients and patients with TB only registered between 2007 and 2011. A hierarchical logistic regression model was applied. RESULTS: Of 6091 cases analysed, 780 (12%) were TB-HIV patients, while 5311 (87%) presented with TB only. TB-HIV patients were more likely to be institutionalised (OR 2.22, 95%CI 1.43-3.46), to present with relapsed TB (OR 5.03, 95%CI 2.02-12.5) and be readmitted after treatment default (OR 16.7, 95%CI 4.34-64.46). They were also more likely to have unfavourable outcomes, including default (OR 2.85, 95%CI 1.81-4.49), death due to TB (OR 2.76, 95%CI 1.27-6.03) and death from other causes (OR 5.59, 95%CI 2.63-11.8). CONCLUSION: Our study highlights the challenges of using national registers for research into childhood TB.

Maximal respiratory pressures among adolescent swimmers.

Maximal inspiratory pressures (MIP) and maximal expiratory pressures (MEP) are useful indices of respiratory muscle strength in athletes. The aims of this study were: to describe the strength of the respiratory muscles of Olympic junior swim team, at baseline and after a standard physical training; and to determine if there is a differential inspiratory and expiratory pressure response to the physical training. A cross-sectional study evaluated 28 international-level swimmers with ages ranging from 15 to 17 years, 19 (61 %) being males. At baseline, MIP was found to be lower in females (P = .001). The mean values reached by males and females were: MIP(cmH2O) = M: 100.4 (± 26.5)/F: 67.8 (± 23.2); MEP (cmH2O) = M: 87.4 (± 20.7)/F: 73.9 (± 17.3). After the physical training they reached: MIP (cmH2O) = M: 95.3 (± 30.3)/F: 71.8 (± 35.6); MEP (cmH2O) = M: 82.8 (± 26.2)/F: 70.4 (± 8.3). No differential pressure responses were observed in either males or females. These results suggest that swimmers can sustain the magnitude of the initial maximal pressures. Other studies should be developed to clarify if MIP and MEP could be used as a marker of an athlete's performance.

Screening and follow-up of children exposed to tuberculosis cases, Luanda, Angola.

This prospective study enrolled children aged < 5 years with reported contact with adult tuberculosis (TB) patients in Angola. The study sample consisted of 124 children: 70 (56.5%) were active TB cases, 22 (17.7%) had latent TB infection (LTBI) and 32 (25.8%) were TB-exposed; 14 (20%) were human immunodeficiency virus positive. After 6 months of follow-up, 31.8% of the LTBI cases had evolved to active TB and 9.4% of the non-infected children had developed active TB. The strategy of simultaneous chest X-ray and TB skin test used in this study was effective; despite this protocol, however, 31.8% LTBI children developed active TB.

Radiographic findings among children hospitalized with severe community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of childhood death. There are few published reports of radiographic findings among children with severe CAP. OBJECTIVE: To describe chest X-ray (CXR) findings and assess association between these radiographic findings and pneumococcal isolation in children with severe CAP. METHODS: A prospective, multicenter, observational study was conducted in 12 centers in Argentina, Brazil, and the Dominican Republic. Children aged 3-59 months, hospitalized with severe pneumonia, were included. On admission, blood and pleural effusion cultures were performed. Streptococcus pneumoniae was identified according to standard procedures in the respective national reference laboratory. Chest X-rays were taken on admission and read before the culture results were reported. RESULTS: Out of 2,536 enrolled patients, 283 (11.2%) had S. pneumoniae isolated, in 181 cases (7.1%) from blood. The follow radiographic patterns were observed: alveolar infiltrate (75.2%), pleural effusion (15.6%), and interstitial infiltrate (9.2%). Overall, pleural effusion was associated with pneumococcal isolation and pneumococcal bacteremia (P < 0.001). Infiltrates were unilateral (78.7%) or bilateral (21.3%), right-sided (76%) or left-sided (24%), in the lower lobe (53.6%) or the upper lobe (46.4%). Multivariate analysis including patients with affection of only one lobe showed that upper lobe affection and pleural effusion were associated with pneumococcal isolation (OR 1.8, 95% CI, 1.3-2.7; OR 11.0, 95% CI, 4.6-26.8, respectively) and with pneumococcal bacteremia (OR 1.7, 95% CI, 1.2-2.6; OR 3.1, 95% CI, 1.2-8.0, respectively). CONCLUSIONS: Three-quarters of the patients studied had alveolar infiltrates. Upper lobe compromising and pleural effusion were associated with pneumococcal invasive disease.

Pulmonary tuberculosis in adolescents: radiographic features.

We studied radiographic features of pulmonary tuberculosis (PTB) described in the report forms for 907 adolescents from two Brazilian cities. A descriptive analysis showed that the most common radiographic lesions were post-primary tuberculosis (53.3%), tuberculous expansile pneumonia (27%) and primary complex with adenomegaly (1.8%). Cavitary lesions occurred in 67/243 (27.6%) patients aged 0-15 years and in 116/321 (36.1%) adolescents aged 16-19 years (P = 0.031). Most of the PTB cases had forms similar to those in adults.

Clinical scoring system for paediatric tuberculosis in HIV-infected and non-infected children in Rio de Janeiro.

The scoring system for diagnosing tuberculosis (TB) used in Brazil has already been validated in human immunodeficiency virus (HIV) negative tuberculous children. Here we studied HIV-positive children. The individuals were divided into four groups: 1) tuberculous infection; 2) other pulmonary diseases; 3a) pulmonary TB and 3b)pulmonary TB and HIV. Group 3a had a significantly higher score than Groups 1 and 2, and Group 1 had a higher score than Group 2. Scores for Group 3b were lower than for Group 3a, although they were still >30 points, which is enough to establish a TB diagnosis (P = 0.0005). The system was useful for the diagnosis of pulmonary TB in HIV-negative and -positive children.

Evolutionary conservation of actin-binding proteins in Trypanosoma cruzi and unusual subcellular localization of the actin homologue.

The actin cytoskeleton controls pivotal cellular processes such as motility and cytokinesis, as well as cell-cell and cell-substrate interactions. Assembly and spatial organization of actin filaments are dynamic events regulated by a large repertoire of actin-binding proteins. This report presents the first detailed characterization of the Trypanosoma cruzi actin (TcActin). Protein sequence analysis and homology modelling revealed that the overall structure of T. cruzi actin is conserved and that the majority of amino-acid changes are concentrated on the monomer surface. Immunofluorescence assays using specific polyclonal antibody against TcActin revealed numerous rounded and punctated structures spread all over the parasitic body. No pattern differences could be found between epimastigotes and trypomastigotes or amastigotes. Moreover, in detergent extracts, TcActin was localized only in the soluble fraction, indicating its presence in the G-actin form or in short filaments dissociated from the microtubule cytoskeleton. The trypanosomatid genome was prospected to identify actin-binding and actin-related conserved proteins. The main proteins responsible for actin nucleation and treadmilling in higher eukaryotes are conserved in T. cruzi.

Brazilian paediatricians' awareness of national guidelines for community-acquired pneumonia.

BACKGROUND: The Integrated Management of Childhood Illness (IMCI) strategy uses simple clinical signs for the diagnosis and severity evaluation of community-acquired pneumonia (CAP). OBJECTIVE: To describe paediatrician awareness of the IMCI strategy for CAP. DESIGN: A cross-sectional study analysing a descriptive case of severe CAP, presented as part of the Brazilian Board of Paediatrician Evaluation (BBPE) tests. RESULTS: Eighty-six (774/898) per cent of paediatricians followed the IMCI protocol to treat CAP. Although hospitalisation was considered in 90% of the answers, only 35% based this decision on lower chest indrawing. CONCLUSION: The BBPE showed that most physicians are aware of the IMCI recommendations.

Heme requirement and intracellular trafficking in Trypanosoma cruzi epimastigotes.

Epimastigotes multiplies in the insect midgut by taking up nutrients present in the blood meal including heme bound to hemoglobin of red blood cell. During blood meal digestion by vector proteases in the posterior midgut, hemoglobin is clipped off into amino acids, peptides, and free heme. In this paper, we compared the heme and hemoglobin uptake kinetics and followed their intracellular trafficking. Addition of heme to culture medium increased epimastigote proliferation in a dose-dependent manner, while medium supplemented with hemoglobin enhanced growth after 3-day lag phase. Medium supplemented with globin-derived peptides stimulated cell proliferation in a dose-independent way. Using Palladium mesoporphyrin IX (Pd-mP) as a fluorescent heme-analog, we observed that heme internalization proceeded much faster than that observed by hemoglobin-rhodamine. Binding experiments showed that parasites accumulated the Pd-mP into the posterior region of the cell whereas hemoglobin-rhodamine stained the anterior region. Finally, using different specific inhibitors of ABC transporters we conclude that a P-glycoprotein homologue transporter is probably involved in heme transport through the plasma membrane.

Evaluation of a proposed diagnostic scoring system for pulmonary tuberculosis in Brazilian children.

In a case-control study to evaluate a systematic scoring system for diagnosing pulmonary tuberculosis (PTB) in children, cases had gastric lavage cultures positive for Mycobacterium tuberculosis and recovered after anti-tuberculosis treatment, while controls had negative cultures and recovered with non-anti-tuberculosis treatment. Radiological aspect (OR = 25.39), contact with a tuberculous adult (OR = 10.67) and tuberculin skin test > or = 10 mm (OR = 8.23) were associated with PTB diagnosis. The sensitivity of the score ranged from 58% to 89% and the specificity from 98% to 86%, with cut-offs of respectively > or = 40 or > or = 30. The scoring system may be a useful diagnostic method in areas with a high prevalence of TB.

Adverse effects of BCG revaccination: a report on 13 cases from Rio de Janeiro, Brazil.

SETTING: BCG revaccination is not used worldwide. In Brazil, it has been recommended since 1994 in children aged 6 to 14 years. Reports in the medical literature of adverse reactions due to revaccination are rare. BCG revaccination remains officially recommended by the Brazilian health authorities, based on the current epidemiological tuberculosis situation in the country. OBJECTIVE: We report 13 cases of children and adolescents with complications due to BCG revaccination. DESIGN: Case reports of patients followed up in a pneumology unit of a university pediatric hospital from May 1996 to December 2000. RESULTS: There were seven males and six females, whose ages ranged from 7-12 years. Adverse reactions occurred between 21 days and 9 months after BCG revaccination. All 13 cases had a scar from prior BCG vaccination. All cases treated received isoniazid, 10 mg/kg/day, in the morning until the end of cure. The duration of treatment varied, but all cases were successfully cured. CONCLUSION: Although adverse reactions are rare, it is important to continue monitoring them in order to learn more about them and to be able to orient health professionals to perform appropriate assessment and timely treatment when they occur.

[Pulmonary involvement in children with AIDS: clinical study and necropsy of 14 cases]. / Acometimento pulmonar em crianças com a síndrome da imunodeficiência humana (AIDS): estudo clínico e de necrópsia de 14 casos.

BACKGROUND: To describe clinical, laboratorial, radiological, and histopathological lung findings from necroscopy of aidetic children with pulmonary disease. MATERIAL AND METHODS: Fourteen children admitted at the Hospital Universitário Antônio Pedro - Universidade Federal Fluminense, Niterói, RJ, and Instituto de Puericultura e Pediatria Martagão Gesteira - Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, between 1989 and 1996, were revised in a retrospective survey. RESULTS: Eight were males (57%). The median age was 1.2 years old (from three months to nine years). Nine children (64.4%) were younger than 24 months old. The HIV transmission was vertical in 10 (71%) children. In these cases, five mothers were contaminated from heterosexual relations. Pneumonia (n=8), oral candidiasis (n=8), and diarrhea (n=5) were the most common previous conditions. The most frequent signs and symptoms on admission were fever (n=12), respiratory distress (n=10), cough (n=10), peripheral lymphadenopathy (n=11), hepatomegaly and/or splenomegaly (n=10), and malnutrition (n=9). The chest x-rays findings were condensation (n=5) and diffuse infiltrates (n=6) patterns. The microscopic lung characteristics were compatibles with pneumonia by cytomegalovirus (CMV) (n=9), bacteria (n=8), Pneumocystis carinii (n=3), Toxoplasma gondii (n=1), Hystoplasma capsulatum (n=1) and Lymphocytic interstitial pneumonia (n=1). The association between CMV and bacteria was observed in six cases. CONCLUSIONS: Age less than two years old, vertical transmission, inespecific clinical presentation of pneumonia, and infiltrates and condensation patterns at the x-rays were the predominant characteristics. Cytomegalovirus and bacteria were the most common etiologic agents, being their association frequent. Lymphocytic interstitial pneumonia and pneumonia by P. carinii were not common causes of pulmonary disease.

Acometimento pulmonar em crianças com a síndrome da imunodeficiência humana (AIDS): estudo clínico e de necrópsia de 14 casos / Necroscopic study of 14 children with AIDS and pneumonia

OBJETIVOS: Descrever os aspectos clínicos, laboratoriais, radiológicos e anatomopatológicos encontrados em tecidos pulmonares de necrópsias de crianças com Aids e acometimento pulmonar. MÉTODOS: Foram revisados, retrospectivamente, prontuários, radiografias simples de tórax e laudos de necrópsias de 14 crianças com Aids e acometimento pulmonar. RESULTADOS: Oito casos eram do sexo masculino e seis do feminino. As idades variaram de três meses a nove anos, mediana de 1,2, sendo nove deles menores de dois anos. A transmissäo foi vertical em 10 pacientes, dos quais cinco mäes tinham história de contaminaçäo por relaçäo heterossexual; três, por hemotransfusäo e em duas, ignorada. Pneumonia (n=8), candidíase oral (n=8) e diarréia (n=5) foram as doenças prévias mais referidas. Os sinais e sintomas observados à internaçäo foram febre (n=12), dispnéia (n=10), tosse (n=11), linfoadenomegalia (n=11), hepato e/ou esplenomegalia (n=10), desnutriçäo (n=9), palidez (n=8), cianose (n=5) e baqueteamento digital (n=2). Os achados radiológicos mais comuns foram infiltrados difusos (n=6) e condensaçöes (n=5). As alteraçöes histológicas pulmonares foram compatíveis com pneumonia pelo citomegalovírus (n=9), por bactérias (n=8), por Pneumocystis carinii (n=3), por Hystoplasma capsulatum (n=1), por Toxoplasma gondii (n=1) e pneumonia intersticial linfocítica (n=1). A associaçäo CMV e bactéria foi observada em seis casos. CONCLUSÖES: Houve predomínio de menores de dois anos, de transmissäo vertical, de quadro clínico inespecífico de doença pulmonar e de infiltrados e condensaçöes à radiografia. Citomegalovírus e bactérias foram os agentes mais comuns, sendo freqüente a sua associaçäo. Pneumonia Intersticial Linfocítica e Pneumonia pelo P. carinii näo foram causas freqüentes de doenças pulmonares

[Relationship between serological diagnosis (ELISA) and severity of pulmonary tuberculosis in children]. / Relação entre o diagnóstico sorológico (ELISA) e a gravidade da tuberculose pulmonar na infância.

Forty eight children from 0 to 13 years old were submitted to the enzyme-linked immunosorbent assay (ELISA) serological test with a view to detect anti PPD IgG antibodies, for diagnosis of pulmonary tuberculosis and to establish the relationship between immune response and radiological gravity of pulmonary tuberculosis (mild, moderate and severe). There were 29 children with pulmonary tuberculosis and 19 children without tuberculosis. The median ELISA optical density were: 0.098 in children with primary complex (mild); 0.092 in children with pneumonic pattern (moderate) and 0.134 in children with miliary tuberculosis (severe). These data show higher positive serological test results in severe forms of pulmonary tuberculosis (p = 0.0007).

[Epidemiology of childhood tuberculosis in the city of Rio de Janeiro, Brazil]. / Epidemiologia da tuberculose infantil na cidade do Rio de Janeiro, RJ.

Data was drawn from a study on the epidemiological trends of tuberculosis among children of Rio de Janeiro county, Brazil. There was an increased incidence of tuberculosis among children and epidemiological health indicators were above the national average.