Pedro Eduardo Almeida da Silva

Inhaled corticosteroids increase the risk of oropharyngeal colonization by Streptococcus pneumoniae in children with asthma

Background and objective:u2003 Recent studies have raised concerns about the link between use of inhaled corticosteroids (ICS) and risk of pneumonia in patients with chronic obstructive pulmonary disease. This cross‐sectional study aimed to investigate the association between ICS and oropharyngeal colonization by Streptococcus pneumoniae (S.u2003pneumoniae) among children (up to 18 years old) with asthma.

Mycobacterium tuberculosis of the RDRio Genotype Is the Predominant Cause of Tuberculosis and Associated with Multidrug Resistance in Porto Alegre City, South Brazil

ABSTRACT Spoligotyping has shown Mycobacterium tuberculosis strains to be composed of different lineages, and some of them are not just geographically restricted but also affect specific ethnic populations and are associated with outbreaks and drug resistance. We recently described a particular subtype within the Latin American-Mediterranean (LAM) family, called RDRio, widespread in Brazil. Moreover, recent data also indicate that RDRio is present in many countries on all continents and is associated with cavitary disease and multidrug resistance (MDR). To further explore the relationship between RDRio and MDR, we conducted a study in a tuberculosis (TB) reference center responsible for the care of MDR patients in Rio Grande do Sul, the southernmost Brazilian state. From a collection of 237 clinical isolates, RDRio alone was responsible for one-half of all MDR cases, including one large group composed of strains with identical IS6110-restriction fragment length polymorphism (RFLP) and having the LAM5 signature. We additionally had complete data records for 96 patients and could make comparisons between the presence and absence of RDRio. No difference in clinical, radiological or laboratory features was observed, but a significantly greater number of cases with MDR were described in patients infected with an RDRio strain (P = 0.0015). Altogether, RDRio was responsible for 38% of all TB cases. These data support and confirmed previous findings that RDRio is the main agent responsible for TB in Brazil and is associated with drug resistance. Considering that RDRio is a globally distributed genotype, such findings raise concern about the increase in MDR in certain human populations.

Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations.

The present study was carried out to investigate the presence of polymorphism in the N-acetyltransferase gene of 41 clinical isolates of Mycobacterium tuberculosis, that were resistant to isoniazid (INH) with no mutations in the hot spots of the genes previously described to be involved in INH resistance (katG, inhA and ahpC). We observed single nucleotide polymorphisms (SNPs) in ten of these, including the G619A SNP in five isolates and an additional four so far un-described mutations in another five isolates. Among the latter SNPs, two were synonymous (C276T, n=1 and C375G, n=3), while two more non-synonymous SNPs were composed of C373A (Leu→Met) and T503G (Met→Arg) were observed in respectively one and two isolates. Molecular modeling and structural analysis based in a constructed full length 3D models of wild type TBNAT (TBNAT_H37Rv) and the isoforms (TBNAT_L125M and TBNAT_M168R) were also performed. The refined models show that, just as observed in human NATs, the carboxyl terminus extends deep within the folded enzyme, into close proximity to the buried catalytic triad. Analysis of tbnat that present non-synonymous mutations indicates that both substitutions are plausible to affect enzyme specificity or acetyl-CoA binding capacity. The results contribute to a better understanding of structure-function relationships of NATs. However, further investigation including INH-sensitive strains as a control group is needed to get better understanding of the possible role of these new mutations on tuberculosis control.

The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples

A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide. To provide a snapshot of NTM species distribution, global partners in the NTM-Network European Trials Group (NET) framework (www.ntm-net.org), a branch of the Tuberculosis Network European Trials Group (TB-NET), provided identification results of the total number of patients in 2008 in whom NTM were isolated from pulmonary samples. From these data, we visualised the relative distribution of the different NTM found per continent and per country. We received species identification data for 20 182 patients, from 62 laboratories in 30 countries across six continents. 91 different NTM species were isolated. Mycobacterium avium complex (MAC) bacteria predominated in most countries, followed by M. gordonae and M. xenopi. Important differences in geographical distribution of MAC species as well as M. xenopi, M. kansasii and rapid-growing mycobacteria were observed. This snapshot demonstrates that the species distribution among NTM isolates from pulmonary specimens in the year 2008 differed by continent and differed by country within these continents. These differences in species distribution may partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location. Species distribution among nontuberculous mycobacteria isolates from pulmonary specimens is geographically diverse http://ow.ly/npu6r

Antimycobacterial and cytotoxicity activity of microcystins

BackgroundThe present work aimed to evaluate the antimycobacterial activity and cytotoxicity of Microcystis aeruginosa toxins, the MC-LR variant and purified extract of [D-Leu1] microcystin-LR.MethodsThe antimicrobial activity of M. aeruginosa extract and microcystin was evaluated by resazurin microtiter assay against Mycobacterium tuberculosis, M. terrae, M. chelonae and M. kansasii. The cytotoxicity assay was performed by trypan blue exclusion against the HTC cell line.ResultsAntimicrobial activity was observed in the hexanic extract of M. aeruginosa (RST 9501 strain) against M. tuberculosis, including sensitive and resistant strains with minimal inhibitory concentrations (MIC) between 1.93xa0μM and 0.06xa0μM. The high activity of M. aeruginosa hexanic extract could be attributed to the major presence of the toxins MC-LR and [D-Leu1] MC-LR that showed activity at MIC between 53 and 0.42xa0μM against tested mycobacterial strains. Even at the highest concentration tested, no toxicity of M. aeruginosa extracts was identified against HTC cells.ConclusionsThese preliminary results suggest that [D-Leu1] MC-LR is a promising candidate for the development of a new antimycobacterial agent.

Detection of Neisseria meningitidis in asymptomatic carriers in a university hospital from Brazil

Asymptomatic meningococcus carriers in hospitals is a risk factor for acquiring meningococcal disease. Meningococcal carrier (MC) frequency was investigated in oropharyngeal swab samples collected from 200 staff members at a teaching hospital from Brazil. MC prevalence was 9% (95% CI 5-13%). Risk factors associated with MC were: mean age of 26.5 years, male gender, bar attendance frequency and number of persons/house. Of 18 isolated meningococcal strains, 14 were non-group able (NG), 3 corresponded to serogroup B and 1 to serogroup 29E. The frequency of serotypes and serosubtypes was heterogenous, with a slight predominance of serotypes 4 and 7 and serosubtypes P1.7 and P1.5. Most strains (n=13) were susceptible to the antimicrobials tested. The ctrA gene (PCR) was identified in 9 (64.3%) of the 14 NG strains, suggesting virulence in most of the NG isolated strains. Therefore, a constant surveillance of these asymptomatic carriers is required.

Anti-tuberculosis activity of oleanolic and ursolic acid isolated from the dichloromethane extract of leaves from Duroia macrophylla

Tuberculosis a major cause of death worldwide, is an infectious disease caused by Mycobacterium tuberculosis. An increase in drug-resistant tuberculosis cases and the emergence of additional resistant strains and coinfections with HIV has stimulated the search for and development of new anti-TB drugs [1]. The wide variety of natural products chemical structures plays a major role on the development of new antimycobacterial drugs generations. Duroia macrophylla is an endemic plant of the Amazon Forest [2]. To the best of our knowledge, no chemical or biological investigations other than ours [3,4] have been carried out on this species as of yet. Hence this work aims to evaluate the antimycobacterial activity of their extracts and isolate and identify the substances present in D. macrophylla active extracts.

Oophoropexy to the Round Ligament after Recurrent Adnexal Torsion

Recurrent adnexal torsion is a rare gynecological emergency. We report a case of recurrent ipsilateral adnexal torsion in a woman with polycystic ovaries, previously submitted to a laparoscopic plication of the utero-ovarian ligament. Due to the recurrence after the plication of the utero-ovarian ligament, the authors performed a laparoscopic oophoropexy to the round ligament, which is an underreported procedure. The patient was asymptomatic for 1u2009year, after which she had a new recurrence and needed a unilateral laparoscopic adnexectomy. Since then, she regained the quality of life without any gynecological symptoms.Oophoropexy to the round ligament may be considered when other techniques fail or, perhaps, as a first option in selected cases of adnexal torsion, as it may allow the prevention of recurrence without increasing morbidity while preserving the adnexa.

Poster 1012: Safety and efficacy of omalizumab in 10 children with asthma and other allergic comorbidities

Methods We retrospectively analyzed the clinical files of all pediatric pts treated with omalizumab from December 2009 to July 2013. The evaluated parameters included: adverse reactions to omalizumab, clinical evolution, Asthma Control Test (ACT) and Severity Scoring of Atopic Dermatitis (SCORAD) score evolution and medication decrease. Statistical significance was defined by a p value in the appropriate nonparametric test lower than 0.05.

PD11 - Omalizumab in children: experience in the Immunoallergology Department

Omalizumab is a monoclonal antibody approved for the treatment of severe allergic asthma for patineis above 6 years old in Europe, but its use has been described successfully in other IgE-mediated diseases.