Streptococcus pyogenes emm Types and Clusters during a 7-Year Period (2007 to 2013) in Pharyngeal and Nonpharyngeal Pediatric Isolates.

Group A streptococcus (GAS) is an important cause of morbidity and mortality worldwide. Surveillance of emm types has important implications, as it can provide baseline information for possible implementation of vaccination. A total of 1,349 GAS pediatric isolates were collected during a 7-year period (2007 to 2013); emm typing was completed for 1,282 pharyngeal (84%) or nonpharyngeal (16%) isolates, and emm clusters and temporal changes were analyzed. Thirty-five different emm types, including 14 subtypes, were identified. The most prevalent emm types identified were 1 (16.7%), 12 (13.6%), 77 (10.9%), 4 (10.8%), 28 (10.4%), 6 (6.8%), 3 (6.6%), and 89 (6.6%), accounting for 82.3% of total isolates. Rheumatogenic emm types comprised 16.3% of total isolates. The emm types 12, 4, and 77 were more prevalent among pharyngeal isolates, and the emm types 1, 89, 6, 75, and 11 were more prevalent among nonpharyngeal isolates. The emm types identified belonged to 13 emm clusters, and the 8 most prevalent clusters comprised 97% of all isolates. There were statistically significant decreases in the prevalence of emm types 12, 4, 5, and 61 and increases in the prevalence of emm types 89, 75, and 11, compared with the period 2001 to 2006. The proposed 30-valent GAS vaccine, which is currently in preclinical studies, encompasses 97.2% of the emm types detected in our study and 97.4% of the erythromycin-resistant strains. In addition, it includes 93.3% of the emm types involved in bacteremia. A much greater diversity of GAS emm types was identified in our area than described previously. Seasonal fluctuations and the introduction of new emm types were observed. Continuous surveillance of emm types is needed in order to evaluate the possible benefits of an M protein-based GAS vaccine.

Rotavirus genotypes co-circulating in Europe between 2006 and 2009 as determined by EuroRotaNet, a pan-European collaborative strain surveillance network.

EuroRotaNet, a laboratory network, was established in order to determine the diversity of co-circulating rotavirus strains in Europe over three or more rotavirus seasons from 2006/2007 and currently includes 16 countries. This report highlights the tremendous diversity of rotavirus strains co-circulating in the European population during three years of surveillance since 2006/2007 and points to the possible origins of these strains including genetic reassortment and interspecies transmission. Furthermore, the ability of the network to identify strains circulating with an incidence of ≥1% allowed the identification of possible emerging strains such as G8 and G12 since the beginning of the study; analysis of recent data indicates their increased incidence. The introduction of universal rotavirus vaccination in at least two of the participating countries, and partial vaccine coverage in some others may provide data on diversity driven by vaccine introduction and possible strain replacement in Europe.

Thiopurine S-methyltransferase genotype and the use of thiopurines in paediatric inflammatory bowel disease Greek patients.

BACKGROUND AND OBJECTIVE: Azathioprine (AZA) and 6-mercaptopurine (6MP) are used in the treatment of paediatric inflammatory bowel disease (IBD). Genetic variations in thiopurine S-methyltranfarase (TPMT) gene have been correlated with enzyme activity and with the occurrence of adverse events to AZA and 6MP. The aim of the present study was to investigate the frequency of the functional TPMT polymorphisms and their association with the occurrence of adverse events during azathioprine therapy in a paediatric IBD cohort. METHODS: Ninety-seven thiopurine-treated paediatric IBD patients (41.24% boys and 58.76% girls) with a mean age 11.25 years (range 3-16), were assessed for TPMT polymorphisms and adverse events. RESULTS: Of the 97 patients enrolled in the study, 18 (18.56%) were heterozygous mutated; two (2.06%) were homozygous for a mutated TPMT gene. Ten patients (10.31%) developed adverse effects, and four of them (40%) had one of the variant alleles. CONCLUSIONS: In this small cohort of subjects, no association was found between TPMT polymorphisms and the occurrence of thiopurines-related adverse events.

Dietary compliance and life style of children with coeliac disease.

BACKGROUND: Coeliac disease (CD) is common and requires a permanent strict gluten-free diet (GFD). However, data concerning how the situation is experienced by children are limited. The present study aimed to investigate the compliance with a GFD and the impact of CD and GFD on the lifestyle of patients and their families, together with proposed recommendations for improvement of quality of life. METHODS: Children with biopsy confirmed CD were recruited consecutively from the outpatient gastroenterology clinic. Participants were evaluated by a special questionnaire for compliance with the GFD, patients' knowledge about CD, and the well-being and lifestyle of children and their families. Comparisons between discrete variables were performed by a chi-square test. RESULTS: Seventy-three children of median age 9.4 (interquartile range = 5-14.5) years were evaluated. Compliance to diet was reported by 58%. Reasons for noncompliance were: poor palatability (32%), dining outside home (17%), poor availability of products (11%), and asymptomatic disease diagnosed by screening (11%). The acceptance of the GFD was reported as good in 65%, whereas avoidance of travelling and restaurants was stated by 17% and 46% of families, respectively. Most families experienced difficulties detecting gluten from the food label. Proposed factors for improvement of quality of life were: better labelling of gluten-containing ingredients (76%) and more gluten-free (GF) foods in supermarkets (58%) and restaurants (42%). CONCLUSIONS: Children with CD have low compliance with the GFD. Better education about the disease, the availability of GF products, and appropriate food labelling could improve compliance and quality of life.

Delayed exposure to infections and childhood lymphomas: a case-control study.

OBJECTIVES: Delayed exposure to common infections during childhood, have been implied to cause strong immunological response to a single infectious agent that eventually triggers leukemogenesis. The aim of the present study was to investigate whether decreased exposure to infections, as reflected in a more seronegative spectrum to several common infectious agents, is associated with increased risk for the development of childhood lymphomas. METHODS: All 125 children (up to 14 years old), with Hodgkin (HL, n = 52) and non-Hodgkin lymphomas (NHL, n = 73) diagnosed through the national network of childhood Hematology-Oncology units during an 8-year period were enrolled in the study along with 125 age- and gender-matched controls. Past exposure to nine common infections [respiratory syncytial virus (RSV), influenza A and B, parainfluenza type 1, adenovirus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV6), Bartonella henselae] was assessed using serological markers. RESULTS: After controlling for possible confounding factors, the overall seronegativity status upon diagnosis was statistically significantly associated with NHL [odds ratio; 95% CI: 1.45 (1.10-1.93), p = 0.01] and less so with HL risk [odds ratio; 95% CI: 1.30 (0.83-2.05), p = 0.25]. A statistically significant association of seronegativity with the development of NHL was evident for RSV [odds ratio; 95% CI: 7.27 (1.59-33.28), p = 0.01], EBV [odds ratio; 95% CI: 6.73 (1.45-31.20), p = 0.01] and suggestive association for influenza B [odds ratio; 95% CI: 2.60 (0.90-7.55), p = 0.08] and influenza A [odds ratio; 95% CI: 2.35 (0.81-6.80), p = 0.11]. In contrast, there was no evidence for association of HL with negative serology for any of the infectious agents tested. CONCLUSIONS: The risk of lymphomas, especially NHL, might be higher when, due to lower exposure to several infectious agents, the relatively unmodulated immune system of a child is challenged by environmental stimuli that can trigger development of lymphomas. The results, however, need further confirmation, through more pertinent methodological designs.

Inflammatory myofibroblastic tumor of the liver due to Mycobacterium tuberculosis in an immunocompetent girl.

The case of a 9-year-old girl with a Mycobacterium tuberculosis inflammatory myofibroblastic tumor (IMT) of the left lobe of the liver is reported. The tumor was surgically excised and had histological features diagnostic of IMT, a positive Ziehl-Nielsen staining for acid-fast bacilli and a positive polymerase chain reaction for Mycobacterium tuberculosis. Surgical excision of the tumor followed by anti-tuberculosis treatment for 9 months resulted in full recovery. The patient had no apparent immune disorder, and there was no evidence of extrahepatic tuberculosis. These findings make this case exceptional because IMTs, due mostly to atypical mycobacteria, have been described only in immunocompromised patients.

Pneumococcal puerperal mastitis in a lactating mother.

INTRODUCTION: A case of pneumococcal mastitis in a breast-feeding mother 6 months postpartum is described. Mastitis is usually caused by Staphylococcus aureus . A review of the literature from 1950 to March 2018 revealed only four other cases in which the causative organism was Streptococcus pneumoniae . CASE PRESENTATION: The nursing mother presented with high fever and the four cardinal signs of inflammation of the left breast: calor, dolor, rubor, tumour. In milk culture Streptococcus pneumoniae was isolated in numbers exceeding 105 c.f.u. ml-1 . The strain was of polysaccharide serotype 11 not included in Prevnar-13. Susceptibility testing showed full sensitivity to ß-lactam antibiotics as well as to macrolides, lincosamides, vancomycin and tetracycline. CONCLUSION: Streptococcus pneumoniae should be considered as a possible causative agent of puerperal mastitis.

Nationwide surveillance of Streptococcus pneumoniae in Greece: patterns of resistance and serotype epidemiology.

This nationwide study assessed the antimicrobial susceptibility and seroprevalence of Streptococcus pneumoniae in paediatric carriage isolates and in clinical isolates from adult pneumococcal disease in Greece during the years 2004-2006. Among 780 isolates recovered from the nasopharynx of children <6 years old attending day-care centres, non-susceptibility rates to penicillin, cefuroxime, ceftriaxone, erythromycin, tetracycline and trimethoprim/sulfamethoxazole were 34.7%, 25.1%, 1.0%, 33.5%, 26.4% and 44.2%, respectively. Among 89 adult clinical isolates, the respective rates were 48.3%, 46.1%, 5.6%, 48.3%, 32.6% and 40.4%. High-level resistance to penicillin, cefuroxime and ceftriaxone was recorded for 14.4%, 23.3% and 0.1% of paediatric carriage isolates, whereas for clinical adult isolates the respective rates were 25.8%, 38.2% and 2.2%. No resistance to levofloxacin and moxifloxacin was recorded, although 3.5% of paediatric carriage isolates and 23.2% of adult clinical isolates had minimum inhibitory concentrations of ciprofloxacin >2mg/L. Serotypes 19F, 14, 23F and 6B were the most prevalent among carriage and clinical isolates. The 7-valent pneumococcal conjugate vaccine was estimated to provide coverage against 71.7% of paediatric carriage isolates and 51.3% of adult clinical isolates. Resistance rates among clinical isolates from adult sources were higher than those recorded among paediatric carriage S. pneumoniae isolates and displayed an increasingly resistant profile compared with previous reports from our country, warranting continuous vigilance.

Prevalence of macrolide resistance genes among staphylococci in Cyprus.

The aims of the present study were to evaluate the frequency of macrolide-resistant staphylococci in Cyprus and to examine the phenotypic and genotypic characteristics of these isolates. Antimicrobial susceptibility testing was performed by broth microdilution method and the macrolide resistance determinants were detected by PCR. The relatedness among the isolates was examined by pulsed-field gel electrophoresis. Ninety-six (67.61%) of the 142 Staphylococcus aureus and 19 (59.4%) of the 32 coagulase-negative staphylococci were resistant to erythromycin. Among the 115 erythromycin-resistant staphylococci, 70 expressed the MLSB-inducible phenotype, 38 the MLSB-constitutive, and 7 the MS. The predominant genes associated with macrolide resistance were the ermA for S. aureus and the ermC for coagulase-negative staphylococci, detected in 90.62% and 47.37% of the isolates respectively. Dissemination of one clone carrying the ermA gene accounted for macrolide resistance in the majority of S. aureus isolates.

A comparative randomised study of valacyclovir vs. oral ganciclovir for cytomegalovirus prophylaxis in renal transplant recipients.

An open, prospective, randomised study was conducted to compare the safety and efficacy of valacyclovir vs. oral ganciclovir for cytomegalovirus (CMV) prophylaxis in renal transplant recipients. Eighty-three renal transplant recipients were assigned randomly to receive valacyclovir (n=43) or oral ganciclovir (n=40) for the first 3 months after transplantation. Both groups were similar in terms of demographics, primary renal disease, graft source, HLA matching, immunosuppressive therapy and donor-recipient CMV antibody status. CMV infection was diagnosed by detection of virus DNA in plasma with the Amplicor CMV Test. CMV disease was observed in only one patient belonging to the ganciclovir group, who developed enterocolitis 6 months post-transplantation. No difference was observed between the two treatment groups with respect to detection of CMV DNA, virus infections other than CMV, acute rejection episodes, and serum creatinine levels at 3 and 6 months following transplantation. An increased number of bacterial infections was noted in the ganciclovir group (p 0.003). No adverse reactions with either treatment were reported. The estimated cost of valacyclovir treatment was 20% higher than that of ganciclovir treatment. Overall, both valacyclovir and oral ganciclovir were found to be effective and safe for CMV prophylaxis in renal transplant recipients. Decisions regarding prophylactic regimens should include additional criteria, such as cost or possible development of resistance.

First cluster of vancomycin-resistant Enterococcus faecalis isolates in Cyprus.

This report describes the first patient in Cyprus to be infected with a vancomycin-resistant enterococcus, as well as the microbiological characteristics of a cluster of vancomycin-resistant enterococcus isolates from the intensive care unit where the index case was hospitalised. All isolates were identified as Enterococcus faecalis, belonged to the same clone, and contained the vanA gene cluster. Transfer of glycopeptide resistance to a susceptible strain of E. faecalis could not be detected.

Evaluation of a rapid beta-lactamase test for detecting ampicillin-resistant strains of Hemophilus influenzae type b.

Chloramphenicol is presently the drug of choice in the initial treatment of serious infections due to Hemophilus influenzae type b. Rapid detection of ampicillin resistance in clinical isolates would facilitate early discontinuation of chloramphenicol therapy in patients infected with ampicillin-sensitive bacteria. A total of 160 strains of H. influenzae type b were tested with a one-hour acidimetric microassay for beta-lactamase activity. All ampicillin-resistant strains rapidly hydrolysed the beta-lactam ring of penicillin. When isolates were encoded and tested without knowledge of their MICs, the 40 ampicillin-resistant strains (MIC greater than or equal to 2 mug/ml) were readily distinguished from 120 sensitive strains. Rapid beta-lactamase assay is therefore a reliable detector of ampicillin resistance in H. influenzae type b.

Cefepine vs. ceftazidime treatment of pyelonephritis: a European, randomized, controlled study of 300 pediatric cases. European Society for Paediatric Infectious Diseases (ESPID) Pyelonephritis Study Group.

BACKGROUND: Cefepime has been used in clinical therapeutic trials for meningitis, serious infection and febrile neutropenia, comprising more than 800 pediatric patients. This agent has also been used in patients 12 years of age and older with uncomplicated and complicated urinary tract infections including pyelonephritis, but not in younger patients. In this study the safety and efficacy of cefepime were compared with those of ceftazidime for treatment of pyelonephritis in pediatric patients younger than 12 years of age. METHODS: Two hundred ninety-nine pediatric patients (ages 1 month to 12 years) with pyelonephritis (300 episodes) were enrolled in a randomized, open label, multicenter trial. Individual results were evaluated by a blinded committee of experts. Cefepime was compared with ceftazidime, both administered parenterally at 50 mg/kg every 8 h. Patients were to receive the assigned study drug until at least 48 h after becoming afebrile. The i.v. treatment was then to be continued or replaced by oral trimethoprimsulfamethoxazole for a maximum of 12 to 14 days. RESULTS: The predominant causative pathogens were Escherichia coli, 88%; Proteus spp., 6%; Pseudomonas aeruginosa, 2%; and Klebsiella spp., 2%. Bacteriologic eradication was achieved in 96 and 94% of cefepime and ceftazidime patients, respectively, at the end of i.v. study drug treatment and was maintained in 94 and 91%, respectively, at the end of total study therapy. After study therapy bacteriologic eradication was maintained after 4 to 6 weeks in 86% of cefepime cases and in 83% of ceftazidime cases. A satisfactory clinical response occurred in 98 and 96% of cefepime and ceftazidime patients, respectively, at the end of i.v. treatment and in 93% at the end of total study therapy in both treatment arms. Drug-related clinical adverse events occurred in 14 cefepime patients (91%) and in 10 ceftazidime patients (7%). CONCLUSIONS: Cefepime and ceftazidime are equally safe and efficacious treatment for pyelonephritis in pediatric patients.

Carriage of Neisseria meningitidis by Greek children: risk factors and strain characteristics.

Oropharyngeal swabs were cultured from 554 children aged 2-19 years attending nurseries, primary schools and secondary schools in the central Athens area. A questionnaire was completed to identify risk factors for carriage. Susceptibility to antimicrobial agents was determined by Etest. The genetic relatedness of the strains was examined by pulsed-field gel electrophoresis (PFGE), and isolate serogrouping was performed by slide agglutination. Twenty-two (4%) children were carriers of Neisseria meningitidis; seven isolates belonged to serogroup C, and five to serogroup B. One isolate was resistant to co-trimoxazole, and five showed intermediate resistance to penicillin. DNA analysis of 16 isolates revealed six distinct PFGE patterns. Clusters with indistinguishable PFGE patterns were noted in the same school. More than one serogroup was included in the same clonal group. On multivariate logistic regression analysis, only age > 12 years remained independently associated with the carrier state (odds ratio, 7.96; 95% CI, 2.24-28.33; p < 0.001). Overall, the N. meningitidis carriage rate among Greek schoolchildren increased with age, and the predominant serogroups in the Athens region were groups C and B. These findings may have important implications for future immunisation strategies with conjugate vaccines.

Detection of tuberculostearic acid in serum and other biological fluids from patients with tuberculosis by electron capture-gas chromatography and chemical ionisation-mass spectrometry.

We analysed 37 clinical samples from 33 patients with bacteriologically confirmed tuberculosis, two cerebrospinal fluid samples from patients with cured tuberculous meningitis, and 14 serum samples from healthy individuals, for the presence of tuberculostearic acid (TSA) by frequency pulsed electron capture-gas chromatography (FPEC-GC) and chemical ionisation gas chromatography-mass spectrometry (CIGC-MS). TSA was detected in 36 of the 37 samples from patients with active tuberculosis and none of the patients with cured tuberculous meningitis; only one of 14 controls generated a similar chromatographic profile. Analysis of biological fluids by FPEC-GC and CIGC-MS for the presence of TSA may be a valuable method for rapid diagnosis of tuberculosis.

Clinical and epidemiological aspects of an enterovirus outbreak in a neonatal unit.

An outbreak of enterovirus infection occurred among neonates in a maternity hospital between July 7 and 22, 1999. Twenty neonates became ill (18 confirmed and two probable), an attack rate of 33%. The incubation period ranged from three to six days (mean, 4.2). The male:female ratio was 11:9 and the mean age at the onset of illness was 5.5 days. All the babies had fever, eight, a maculopapular rash, and six had symptoms of gastroenteritis, 11 developed meningitis. Nineteen neonates required hospitalization for three to seven days, but all were discharged home without sequelae. Enteroviral RNA was detected in all of 18 urines, and 14 cerebrospinal fluid specimens tested. A case-control study was conducted to determine risk factors associated with the outbreak. Rooming in the nursery ward was a significant risk factor (odds ratio=33.35; 95% confidence interval, 3.79-800; P=0.00002). No association was found between illness and other possible risk factors. Appropriate control measures resulted in resolution of the outbreak. Our findings demonstrate the potential for enteroviruses to cause widespread illness among newborns, and emphasize the usefulness of polymerase chain reaction in the early diagnosis of infection, and underline the role of effective control measures in interrupting viral transmission.

Epidemiology of invasive childhood pneumococcal infections in Greece.

UNLABELLED: A retrospective study was conducted to identify the epidemiologic characteristics of invasive pneumococcal infections among children <14 y of age in our geographic region. During a 5-y period, from 1995 to 1999, 590 cases of invasive pneumococcal infection were identified in Aghia Sophia Children's Hospital, Athens, Greece. The male to female ratio was 1.4:1 and 64% of patients were younger than 5 y of age. The overall annual incidence rate was estimated as 44/100,000 children <14y of age, whereas the incidence rate for children <5y of age was 100/100,000. The most common types of infections were pneumonia (472 cases; 133 definite and 339 probable), bacteraemia without focus (79 cases), and meningitis (33 cases). A seasonal variation of invasive pneumococcal infections was noted, with two peaks--one during spring and the other during autumn. Only two cases with meningitis died and one developed permanent neurological sequelae, representing a case-fatality rate for meningitis of 6%. Serogroups 14, 19, 6, 18, 23, 4 and 9 were the most prevalent, comprising 77% of 92 serotyped isolates. CONCLUSION: Invasive pneumococcal infections cause considerable morbidity in the paediatric population in the Athens metropolitan area. Sixty-six percent of the serotypes causing invasive pneumococcal disease in our region are included in the 7-valent conjugate vaccine.