Kalliopi Theodoridou

Prognostic factors related to sequelae in childhood bacterial meningitis: Data from a Greek meningitis registry

BackgroundBacterial meningitis (BM) is a life-threatening disease, often related with serious complications and sequelae. Infants and children who survive bacterial meningitis often suffer neurological and other sequelae.MethodsA total of 2,477 patients aged 1 month to 14 years old hospitalized in a Childrens Hospital in Greece diagnosed with acute bacterial meningitis were collected through a Meningitis Registry, from 1974 to 2005. Clinical, laboratory and other parameters (sex, age, pathogen, duration of symptoms before and after admission) were evaluated through univariate and multivariate analysis with regard to sequelae. Analysis of acute complications were also studied but not included in the final model.ResultsThe rate of acute complications (arthritis and/or subdural effusion) was estimated at 6.8% (152 out of 2,251 patients, 95%CI 5.8-7.9) while the rate of sequelae (severe hearing loss, ventriculitis, hydrocephalus or seizure disorder) among survivors was estimated at 3.3% (73 out of 2,207 patients, 95%CI 2.6-4.2). Risk factors on admission associated with sequelae included seizures, absence of hemorrhagic rash, low CSF glucose, high CSF protein and the etiology of meningitis. A combination of significant prognostic factors including presence of seizures, low CSF glucose, high CSF protein, positive blood culture and absence of petechiae on admission presented an absolute risk of sequelae of 41.7% (95%CI 15.2-72.3).ConclusionsA combination of prognostic factors of sequelae in childhood BM may be of value in selecting patients for more intensive therapy and in identifying possible candidates for new treatment strategies.

Time trends in pediatric hospitalizations for varicella infection are associated with climatic changes: a 22-year retrospective study in a tertiary Greek referral center.

Background/Aims The transmission rate of air-borne infectious diseases may vary secondary to climate conditions. The study assessed time trends in the seasonality of hospitalized varicella cases in a temperate region in relation to climatic parameters prior to the implementation of universal varicella immunization. Methods A retrospective descriptive study was conducted among all pediatric and adolescent varicella patients (n = 2366) hospitalized at the “Aghia Sophia” Childrens Hospital during 1982–2003 in Athens, Greece. Date of infection was computed based on hospital admission date. Seasonal and monthly trends in the epidemiology of varicella infection were assessed with time series analysis (ARIMA modeling procedure). The correlation between the frequency of varicella patients and the meteorological parameters was examined by the application of Generalized Linear Models with Gamma distribution. Results During 1982–2003, the occurrence of hospitalized varicella cases increased during summer (p = 0.025) and decreased during autumn (p = 0.021), and particularly in September (p = 0.003). The frequency of hospitalized varicella cases was inversely associated with air temperature (p<0.001). In contrast, the occurrence of hospitalized varicella cases was positively associated with wind speed (p = 0.009). Conclusions Pediatric hospitalizations for varicella infection rates have increased during summer and decreased during autumn in the examined temperate region. Time trends in hospitalized varicella cases are associated with climatic variables.

Non-traditional adipokines in pediatric HIV-related lipodystrophy: a-FABP as a biomarker of central fat accumulation

Abstract Background. Lipodystrophy characterized by adipose tissue redistribution and lipid and glucose metabolism abnormalities, is common among HIV-infected adults and children on highly-active-antiretroviral-therapy (HAART). In a previous study of HIV-infected children, we did not detect insulin resistance, despite a high percentage of body fat redistribution abnormalities. Aim of the study. To investigate the non-traditional adipokines Retinol-binding-Protein-4 (RBP4), neutrophil-gelatinase-associated-lipocalin (NGAL), a-Fatty-Acid-Binding-Protein (a-FABP) and YKL-40 in HIV-infected children on highly-active-antiretroviral-therapy and evaluate their possible association to lipodystrophic changes or insulin resistance. Methods. Seventeen vertically HIV-infected children (mean age: 12.5 years, mean duration of HAART: 5.2 years) and 20 age- and BMI-matched controls were recruited. The HIV-children were re-evaluated after 12 months. RBP4, NGAL, a-FABP and YKL-40 were assessed at study entry and 12 months later and were correlated to body fat content and insulin resistance. Results. RBP4 values were similar at study entry and 12 months later in HIV-children and controls and showed no correlation to body fat or insulin resistance. NGAL was lower in HIV children at study entry but normalized after 12 months with no positive correlation to insulin resistance. a-FABP was positively correlated to body fat content, especially to trunk fat, both at initial evaluation and at follow-up in HIV children and, after prolonged highly-active-antiretroviral-therapy, it was also positively correlated to insulin resistance. Conclusions. This study is the first one to demonstrate that a-FABP could be a useful marker in unraveling central fat accumulation in HIV-infected children on highly-active-antiretroviral-therapy. Large prospective studies are needed to confirm these results.

Pertussis Epidemiology in Greece and Emerging Risk Groups during the Vaccination Era (1980–2008)

To study the epidemiology of pertussis in Greece and epidemiologic changes throughout a period of twenty-nine years, we conducted a retrospective analysis of available data of pertussis cases for the past twenty-nine years (1980–2008) and a prospective analysis of hospitalized pertussis cases from a childrens hospital in Athens for eight years (2001–2008). From 1980 through 2008, the incidence of pertussis in Greece declined from 11.2 to 0.05 cases per 100,000. Epidemic cycles occurring every 3 to 5 years were observed. Since pertussis circulation cannot be fully controlled by present immunization programs, efforts should be made to vaccinate infants at the recommended age, early diagnose, treatment as well as contact tracing of pertussis cases. Control of pertussis in social susceptible populations is necessary. A national program with adolescent and adult booster could decrease the circulation of B. pertussis. Despite an overall decrease for pertussis cases, pertussis is still a present and future challenge of public health service in Greece.

A Case-Control Study on the Risk Factors for Meningococcal Disease among Children in Greece

Purpose The aim of this study was to identify environmental or genetic risk factors that are associated with invasive meningococcal disease (IMD) in children in Greece. Methods A case-control study was performed in 133 children (44 cases and 89 controls) aged between 0–14 years, who were hospitalized in a childrens hospital in Athens. Demographics and possible risk factors were collected by the use of a structured questionnaire. To investigate the association of mannose binding lectin (MBL) with IMD, a frequency analysis of the haplotypes of the MBL2 gene and quantitative measurement of MBL serum protein levels were performed using Nanogen NanoChipR 400 technology and immuno-enzyme techniques, respectively. Results The multivariate analysis revealed that changes in a childs life setting (relocation or vacation, OR = 7.16), paternal smoking (OR = 4.51), upper respiratory tract infection within the previous month (OR = 3.04) and the density of people in the house/100m2 (OR = 3.16), were independent risk factors associated with IMD. Overall 18.8% of patients had a MBL2 genotype with low functionality compared to 10.1% of healthy controls, but this was not statistically significant (p = 0.189). Conclusion Prevention strategies aimed at reducing parental smoking and other risk factors identified in this study could decrease the risk of IMD among children in Greece.

Time trends in pediatric hospitalizations for hepatitis A in Greece (1999–2013): Assessment of the impact of universal infant immunization in 2008

ABSTRACT Hepatitis A vaccine was introduced in the Greek National Immunization Program in 2008. To estimate possible impact of the universal vaccination implementation, time trends of hospitalizations for hepatitis A at the Infectious Diseases Unit of a Tertiary Pediatric Hospital in Athens during 1999–2013 were analyzed. Hepatitis A hospitalizations were recorded from the discharge database and were expressed as frequencies and rate of annual departmental hospitalizations. Time series analysis (ARIMA) was used to explore trends and the impact of the vaccination. Moreover, changes in patient age, population group distribution and the duration of hospitalization were also examined. Hepatitis A hospitalizations rate significantly decreased between pre-vaccination (1999–2008) and post-vaccination (2009–2013) era from 50.5 to 20.8/1000 hospitalizations (p = 0.005). A 3-year periodicity and a trend of reduction on hepatitis A hospitalizations rates across years were noted. Roma children had significant higher rates of hepatitis A hospitalization, followed by immigrant children. Importantly, possibly due to preceding vaccine availability with considerable uptake in private market and unvaccinated group/pockets of children (Roma), overall vaccination effect was less apparent when compared to data from other countries that implemented universal vaccination. No significant change in patient age, population group distribution, or duration of hospitalization was observed. High risk groups such as Roma children should be targeted for vaccination to reduce future outbreaks.

Association of treatment for bacterial meningitis with the development of sequelae.

BACKGROUND Bacterial meningitis continues to be a serious, often disabling infectious disease. The aim of this study was to assess the possibility that treatment influences the development of sequelae in childhood bacterial meningitis. METHODS Two thousand four hundred and seventy-seven patients aged 1 month to 14 years with acute bacterial meningitis over a 32-year period were enrolled in the study. Data were collected prospectively from the Meningitis Registry of a tertiary university teaching hospital in Athens, Greece. Treatment was evaluated through univariate and multivariate analysis with regard to sequelae: seizure disorder, severe hearing loss, ventriculitis, and hydrocephalus. RESULTS According to the multinomial logistic regression analysis, there was evidence that penicillin, an all-time classic antibiotic, had a protective effect on the occurrence of ventriculitis (odds ratio (OR) 0.17, 95% confidence interval (CI) 0.05-0.60), while patients treated with chloramphenicol had an elevated risk of ventriculitis (OR 17.77 95% CI 4.36-72.41) and seizure disorder (OR 4.72, 95% CI 1.12-19.96). Cephalosporins were related to an increased risk of hydrocephalus (OR 5.24, 95% CI 1.05-26.29) and ventriculitis (OR 5.72, 95% CI 1.27-25.76). The use of trimethoprim/sulfamethoxazole increased the probability of seizure disorder (OR 3.26, 95% CI 1.08-9.84) and ventriculitis (OR 8.60, 95% CI 2.97-24.91). Hydrocortisone was associated with a rise in hydrocephalus (OR 5.44, 95% CI 1.23-23.45), while a protective effect of dexamethasone (OR 0.82, 95% CI 0.18-3.79) was not statistically significant. CONCLUSIONS Current study findings suggest that the type of antimicrobial treatment for childhood bacterial meningitis may influence in either a positive or a negative way the development of neurological sequelae.

Time trends in pediatric Herpes zoster hospitalization rate after Varicella immunization.

Herpes zoster (HZ) is an emerging concern for public health officials. The aim of this study was to determine whether universal Varicella immunization implemented in 2004 had an impact on HZ hospitalization in immunocompetent children in Greece. All HZ hospitalizations were recorded during the period 1999–2011. The overall attributable hospitalization rate was 13.89 cases/1000 hospital admissions (95%CI: 11.69–16.38 cases/1000 hospital admissions). HZ hospitalization rate remained unchanged during the study period. These data provide a basis for monitoring HZ hospitalization rate among children following universal toddler immunization.

Use of Galactomannan Antigen and Aspergillus DNA Real-time Polymerase Chain Reaction as Routine Methods for Invasive Aspergillosis in Immunosuppressed Children in Greece

PURPOSE Invasive aspergillosis (IA) remains a critical issue in immunosuppressed patients. Detection of galactomannan antigen (GM) in serum samples is included as a criterion of IA by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group. Nevertheless, Aspergillus DNA detection by polymerase chain reaction (PCR) has not yet been included because clinical data validation is lacking. The present study describes the simultaneous performance of GM and PCR tests as routine methods for IA diagnosis. METHODS During the period January 2012 to December 2017, a total of 156 white children hospitalized in a tertiary childrens hospital of Athens (97 boys and 59 girls; age range, 5 months-14 years) were examined as possible cases of IA. Patients were classified into 4 groups based on their underlying diseases: hematologic malignancies (107 of 156 [68.6%]), solid tumors (16 of 156 [10.2%]), primary immunodeficiency (12 of 156 [7.7%]), and hereditary immunodeficiency (21 of 156 [13.5%]). GM detection was made with the Platelia Aspergillus Ag kit (Bio-Rad Laboratories, Hercules, California). Sera with a cut-off index ≥0.5 on at least 2 separate blood collections were considered positive. Serum detection of Aspergillus DNA was conducted with real-time PCR MycAssay Aspergillus assay (Myconostica Ltd, Cambridge, United Kingdom). PCR positivity was determined by using a threshold of 38 cycles in at least 1 serum sample. Four or more successive samples per patient were tested. FINDINGS Overall, 28 of 156 patients (53 of 744 serum samples) were found positive. Eleven patients were positive using both methods (24 samples). Four children were positive only by PCR (6 samples), whereas 13 (23 samples) were positive only with GM in consecutive samples. Agreement of both methods, GM(+)/PCR(+) or GM(-)/PCR(-), was found in 139 patients (90% of total patients) and 715 samples (96.1% of total samples). The agreement of both methods was found: (1) 85% in patients with hematologic malignancies; (2) 100% in patients with solid tumors; (3) 97.5% in patients with primary immunodeficiency; and (4) 98.8% in patients with hereditary immunodeficiency. Overall disagreement was observed in 17 patients, in which the positive result in any of the 2 methods was estimated as true positive in conjunction with radiologic and other clinical findings. IMPLICATIONS The combination of GM and PCR, provided high diagnostic accuracy in consecutive samples (twice a week). Clinical, radiologic, and other laboratory findings should be taken into consideration in the evaluation of GM and PCR.

Preparedness of adolescents departing from Athens International Airport to Africa or Asia: A five-year airport-based prospective study

BACKGROUND The number of adolescents who travel has increased. We estimated the preparedness of adolescents (12-18 years) departing from Athens to Africa and Asia. METHODS An airport-based survey was conducted from 2011 to 2015. RESULTS Sixty-eight adolescents participated; 27/68 (40%) had the Greek nationality. Their main destinations were the Indian subcontinent (37%) and South-East Asia (32%). Most adolescents planned to stay for <1 month (69%) or for 1-3 months (22%). Their main purpose for travel was to visit friends and relatives (VFRs) (60%). Compared to non-VFR adolescents, VFRs more frequently travelled to sub-Saharan Africa and Southeast Asia, stayed in local residences and for longer periods. Twenty-one (31%) adolescents sought pre-travel counseling (in 57% of cases 8-14 days before departure). Having the Greek nationality was the only significant factor associated with an increased probability for seeking pre-travel counseling. Vaccination against rabies, typhoid fever, Japanese encephalitis and meningococcus was highly inadequate for adolescents travelling to endemic areas. Significant gaps in malaria chemoprophylaxis were found in those travelling to the Indian subcontinent. CONCLUSIONS Less than one third of adolescents travelling to Africa and Asia seek counseling. There is a need to access adolescent travellers in Greece and improve pre-travel vaccinations and malaria chemoprophylaxis.