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Yang Y.,Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics Capital Medical University
BMC infectious diseases | Year: 2014

In this study, we defined the population biology of serogroup 6 Streptococcus pneumoniae collected in China and their antibiotic resistance profiles. The serotypes of 225 S. pneumoniae strains isolated between 1997 and 2011 were identified with the Quellung reaction and serotype-specific PCR. All isolated pneumococci were tested for their sensitivity to 11 kinds of antibiotics with the E-test method or disc diffusion. The sequence types (STs) were analyzed with multilocus sequence typing (MLST). The frequencies of serotypes and subtypes 6A, 6B-I, 6B-II, 6C, and 6D among the 225 isolates were 46.7% (105/225), 19.6% (44/225), 25.8% (58/225), 6.2% (14/225), and 1.8% (4/225), respectively. Serotype 6E was not found in the serotype 6A isolates, and neither serotype 6F nor 6G was identified in any isolate. MLST analysis revealed 58 STs. The most common STs were ST982 (23.1%), ST90 (14.7%), ST4542 (7.6%), and ST2912 (4.9%). The rates of clonal complex 90 (CC90) and CC386 among the oral-penicillin-nonsusceptible isolates decreased over the years, whereas the rates of CC855 and CC3173 increased. The four CCs had similar penicillin MIC distributions, with a maximum MIC of 2 μg/ml. This study identified the serotypes/subtypes and CCs/STs of group 6 S. pneumoniae present in China. No salient antibiotic-resistant clones were isolated among the serogroup 6 S. pneumoniae.


PubMed | Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics Capital Medical University
Type: Journal Article | Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases | Year: 2011

Genetic factors of human susceptibility to tuberculosis (TB) are multiple and their effect may be ethnic- and age-dependent. TNFR2 encoded by the TNFRSF1B gene is one of the important TNF- receptors; its polymorphisms were previously suggested as potential markers of host susceptibility to TB. Here, genotyping of three SNPs in TNFRSF1B 3UTR (rs1061624, rs5030792, rs3397) was performed in Han Chinese pediatric population (229 TB patients and 233 control subjects). rs5030792 was found homozygous (TT genotype) in all studied individuals. The rs3397-T allele was almost equally represented in both gender groups in this study; in particular, it was detected in 33.9% and 35.2% in female cases and controls, respectively (P=0.8). This latter result differs strikingly from an African study where rs3397-T was found in only 12.8 and 16.2% of Ghanaian female cases and controls, respectively (P=0.007 [Mller et al., 2010. Am. J. Respir. Crit. Care. Med. 181, 388-393]). In contrast, rs1061624-A allele, acting recessively, was found to be a possible risk factor for clinical TB in females (P=0.03). The rs1061624 heterozygotes were overdominant in controls versus patients (P=0.015) that warrants further study of their hypothetical advantage in TB. Neither of the common haplotypes was associated with susceptibility to TB. Compared to the published contrasting data on African (7-15%) and European (57%) populations, GTT haplotype was found in an intermediate frequency (26%). Further studies on both adult and pediatric populations in ethnically diverse settings are needed to elucidate the functionality of these 3UTR SNPs of the TNFR2 gene.


PubMed | Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics Capital Medical University and Shandong University
Type: Journal Article | Journal: PloS one | Year: 2015

To investigate changes in virulence-related genotypes and in the antimicrobial susceptibility of Bordetella pertussis isolates collected from the 1970s to 2014 in the northern part of China.A total of 124 B. pertussis isolates from three periods, the 1970s, 2000-2008, and May 2013-Sept 2014, were typed by multilocus sequence typing (MLST) and tested for antimicrobial susceptibility and virulence-related genes. A fragment of the 23S rRNA gene from each of the 99 isolates from 2013-2014 was amplified and sequenced.All isolates from 2000-2008 and 2013-2014 were identified as ST2, whereas isolates from the 1970s were ST1. PtxA2/ptxC1/ptxP1/prn1/fim2-1/fim3-1/tcfA2, which was the same as the vaccine strain, was the only type in the 1970s. During the 2000s and 2013-2014, the virulence type ptxA1/ptxC1/ptxP1/prn1/fim2-1/fim3-1/tcfA2 was dominant, with frequencies of 68.4% and 91.9%, respectively. Nine ptxP3 strains, which were more virulent, were detected after 2000. All 124 isolates were susceptible to levofloxacin, sulphamethoxazole/trimethoprim and tetracycline. The isolates from the 1970s and 2000-2008 were susceptible to all tested macrolides, whereas 91.9% of the 2013-2014 isolates were highly resistant (minimal inhibitory concentration, MIC >256 g/ml). No ptxP3 strain was resistant to macrolides. All erythromycin-resistant strains except for one had the A2047G mutation in the 23S rRNA gene.Macrolide resistance of the B. pertussis population has been a serious problem in the northern part of China. Because most of the epidemic clone of the pathogen expresses the same antigen profiles as the vaccine strain, except ptxA, improvements in immunization strategies may prevent the spread of infection and drug resistance.


PubMed | Capital Medical University and Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics Capital Medical University
Type: Journal Article | Journal: BMC infectious diseases | Year: 2016

Data regarding HIV-seronegative pediatric patients with cryptococcal meningitis (CM) have been very limited.We retrospectively reviewed non-HIV-infected in patients with CM from January 2002 through December 2013 in Beijing Childrens Hospital. Records of the all patients were obtained and compared.The 34 children had a median age of 5.6years. Most of the patients were male (67.6%). Only 23.5% of the cases had identifiable underlying diseases. The sensitivity of the CSF cryptococcal antigen, India ink smear and CSF culture in our study were 81.5, 85.3 and 82.4%, respectively. And the sensitivity of combinations of these tests was 91.2%. Out of the 34 patients, 16 (47.1%) had other organs involvement in addition to the brain. The main abnormal features via magnetic resonance imaging (MRI) were Virchow-Robin space dilatation (44.4%), hydrocephalus (38.9%), gelatinous pseudocysts (33.3%), brain atrophy (33.3%), meningeal enhancement (27.8%) and local lesions (27.8%). In total, 64.7% of the patients were successfully treated at discharge, whereas treatment failed in 35.3% of the patients.Cryptococcal meningitis is an infrequent disease with a high fatality rate in children in China. The majority of patients were apparently healthy. Clinicians should consider cryptococcal infection as a potential pathogen of pediatric meningitis. Cryptococcal antigen, India ink smear and culture tests are recommended for diagnosis.


PubMed | Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics Capital Medical University
Type: | Journal: BMC infectious diseases | Year: 2014

In this study, we defined the population biology of serogroup 6 Streptococcus pneumoniae collected in China and their antibiotic resistance profiles.The serotypes of 225 S. pneumoniae strains isolated between 1997 and 2011 were identified with the Quellung reaction and serotype-specific PCR. All isolated pneumococci were tested for their sensitivity to 11 kinds of antibiotics with the E-test method or disc diffusion. The sequence types (STs) were analyzed with multilocus sequence typing (MLST).The frequencies of serotypes and subtypes 6A, 6B-I, 6B-II, 6C, and 6D among the 225 isolates were 46.7% (105/225), 19.6% (44/225), 25.8% (58/225), 6.2% (14/225), and 1.8% (4/225), respectively. Serotype 6E was not found in the serotype 6A isolates, and neither serotype 6F nor 6G was identified in any isolate. MLST analysis revealed 58 STs. The most common STs were ST982 (23.1%), ST90 (14.7%), ST4542 (7.6%), and ST2912 (4.9%). The rates of clonal complex 90 (CC90) and CC386 among the oral-penicillin-nonsusceptible isolates decreased over the years, whereas the rates of CC855 and CC3173 increased. The four CCs had similar penicillin MIC distributions, with a maximum MIC of 2 g/ml.This study identified the serotypes/subtypes and CCs/STs of group 6 S. pneumoniae present in China. No salient antibiotic-resistant clones were isolated among the serogroup 6 S. pneumoniae.


PubMed | Capital Medical University and Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics Capital Medical University
Type: Journal Article | Journal: PloS one | Year: 2015

Interferon Gamma Release Assays (IGRAs) were developed for the indirect or immunologic diagnosis of tuberculosis infection; however, they have also been used to assist in difficult to diagnose cases of tuberculosis disease in adults, and to a lesser extent, in children, especially in those under 5 years old. We evaluated the utility of using an IGRA in pediatric tuberculosis in younger children in a hospital setting. The diagnostic accuracy of T-SPOT.TB and TST was assessed in 117 children with active tuberculosis and 413 children with respiratory tract infection. Sensitivity and specificity were calculated for the tests used individually and together. Concordance was also calculated. Sensitivity of T-SPOT.TB (82.9%) was higher than TST (78.6% using a 5mm cut-off), especially in children confirmed to have TB. T-SPOT.TB was more specific than TST using a 5mm cut-off (96.1% vs. 70.9%). Combining T-SPOT.TB and TST results improved the sensitivity to 96.6%. In conclusion, the results of the current study indicate that T-SPOT.TB has good sensitivity and specificity, supporting its use among patients of this age. A combination of IGRA and TST would be useful additions to assist in the diagnosis of childhood TB.


PubMed | Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics Capital Medical University
Type: Journal Article | Journal: Molecular biology reports | Year: 2013

Host genetic factors play a major role in determining differential susceptibility to human tuberculosis (TB), a re-emerging infectious disease throughout the world. Genetic variations in the IFNG gene coding for interferon gamma (IFN-), have been identified in TB patients. To investigate the association of the IFNG polymorphisms with TB susceptibility in Chinese pediatric population. A case-control study of 189 TB patients and 164 controls was performed using single-nucleotide polymorphism (SNP) analysis. Genomic DNA was extracted from leukocytes in peripheral blood. Three SNPs of IFNG, including -1616C/T (rs2069705), +874A/T (rs2430561), and +3234C/T (rs2069718), were selected for genotyping and analysis. The +874A and +3234C alleles were more frequent among TB patients (P=0.108 and P=0.088), especially in females (both P=0.029), although this difference was not significant since Bonferroni corrected significance threshold was 0.025 (two of three SNPs were found to be in linkage disequilibrium). More pronounced differences for the +874 and +3234 polymorphisms were found under the genotype comparison between TB cases and controls in the total population [P=0.026 (borderline non-significance) and P=0.020, respectively], and in the female subgroup (P=0.020 and P=0.020). The dominant model of inheritance was shown to be significant for +874A and +3234C alleles (both P=0.019) in the female subgroup. The +874A and +3234C alleles were more frequently found in extrapulmonary TB patients than in controls (P=0.039). Haplotype analysis carried out on these three SNPs showed the TTT haplotype to be more frequent in controls than in TB cases, and this difference showed a strong significance (P=0.005). The +874A and +3234C alleles may be related to TB susceptibility in the female subgroup in the Chinese pediatric population of North China. The higher rate of +874A (known to correlate with lower IFN- expression) in the extrapulmonary TB subgroup suggests a sufficient IFN- expression to be not only an important factor for the onset of TB disease but also for limiting its dissemination to lungs.

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