Interferon gamma inducible protein-10 in the diagnosis of paediatric tuberculosis infection in a low TB incidence country.

OBJECTIVE: To assess interferon-gamma inducible protein 10 (IP-10) as a diagnostic marker for tuberculous infection in children, particularly in relation to its differential diagnostic performance in young children. DESIGN AND RESULTS: A case-control study was conducted among 161 children and adolescents (mean age 6.3 years ± standard deviation 1.7; males n = 79, 49%). Fifty-four (33.5%) had active TB, 53 (33%) had latent tuberculous infection (LTBI), and 54 (33.5%) were non-LTBI controls. Unstimulated IP-10 levels did not differ between groups (P > 0.05 for all comparisons). TB-specific antigen stimulated IP-10 levels were more profoundly increased in infected groups than in controls (P < 0.001 for all comparisons). None of the IP-10-based diagnostic indexes demonstrated the ability to discriminate active disease from LTBI. A value of IP-10 ⩾ 1222 pg/ml had 83.3% sensitivity, 79.6% specificity, 80.4% positive predictive value and 82.7% negative predictive value for the diagnosis of LTBI. IP-10 based indexes demonstrated a trend towards better performance in the population group aged <5 years. CONCLUSION: The IP-10 assay could be useful in improving the diagnosis of LTBI in patients aged <5 years in combination with existing interferon-gamma release assays.

Pandemic influenza A vs seasonal influenza A in hospitalized children in Athens.

BACKGROUND: Data on pandemic H1N1 influenza (pH1N1) virus infection in hospitalised children are limited. AIMS AND OBJECTIVES: To examine the epidemiological and clinical characteristics of children hospitalised with pH1N1 at a large tertiary-care centre in Athens and compare them with those of children hospitalised with seasonal influenza A in previous years. METHODS: All children (n = 146) admitted with confirmed pH1N1 between October 2009 to February 2010 and January 2011 to May 2011 were included. Data on children ≧ 6 months of age (n = 109) were compared with those of 138 children admitted with seasonal influenza A who were examined during two previous influenza seasons (2002-2003 and 2004-2005). RESULTS: The age distribution was similar between seasonal and pandemic H1N1. Bronchial asthma was significantly more common in the seasonal influenza group but the clinical presentation was similar in the two groups, except that fever was more common in patients with pH1N1. Children admitted with seasonal influenza were more likely to develop acute otitis media. There were no significant differences between the two groups for severe outcomes (admission to the ICU, mechanical ventilation or death). Only one child with seasonal influenza (0.6%) and three with pH1N1 influenza (2%) required admission to the ICU. Mean length of hospitalisation was longer in the seasonal influenza group. CONCLUSION: Clinical manifestations were similar between pH1N1 and seasonal influenza, and the pandemic virus did not appear to cause more severe disease in hospitalised children.

Trends in the epidemiology of childhood tuberculosis in Greece.

SETTING: A hospital referral center for childhood tuberculosis (TB). OBJECTIVE: To evaluate the epidemiological and clinical features of childhood TB in the Greater Athens area in the last decade. DESIGN: We retrospectively reviewed the medical records of patients aged <14 years treated for active TB between January 2000 and December 2009 at our pediatric TB clinic and compared the results with the patient turnover during the previous decade (1990-1999). Data concerning demographic and clinical characteristics were analyzed. RESULTS: A total of 321 children (median age 5.57 years, 157 males) with active TB were identified. About one third originated from areas where TB was previously recognized to be highly endemic. Twenty-three children (7%) had extra-pulmonary TB, and 61% of them originated from TB-endemic areas. Bacteriological confirmation was obtained in 40% of patients from whom specimens were obtained: 1 of 26 (3.8%) strains was multidrug-resistant. Most cases with drug-resistant Mycobacterium tuberculosis were noted among immigrant children. The average annual TB incidence was estimated at 5.37 per 100 000 for children aged <14 years in the Greater Athens area. Time trend analysis for the 20-year period revealed a significant reduction in the total number of TB cases (P = 0.002) and in TB among children from low-incidence countries (P < 0.0001). CONCLUSIONS: In our settings, active TB is decreasing among children of Greek origin; disease epidemiology and drug resistance is influenced by the increasing influx of immigrants from areas where the disease is highly prevalent.

Latent tuberculosis infection in children: diagnostic approaches.

Tuberculosis (TB) remains an important public health problem and a leading infectious cause of death. Diagnosis and treatment of latent tuberculosis infection (LTBI) is important for TB control and elimination. Nevertheless, the diagnosis of LTBI in both adults and children remains complex, since there is no gold standard. The development of interferon gamma release assays was a major breakthrough in the diagnosis of LTBI. The evaluation of IGRAs in the diagnosis of LTBI in children is proven to be difficult since childhood TB differs from adults as immune responses vary with age. Separate studies assessing IGRAs performance in children are still limited, and only a few of them divide results by narrow age groups Nevertheless, new approaches are being exploited by the ongoing research for the development of more efficient diagnostic tools. It is likely that many changes in both the diagnosis and management of LTBI will occur in the near future. We believe that better understanding of the immunopathology of latency can ultimately lead to the development of more effective strategies in TB control. In the present review we summarize current data on diagnosis of LTBI in children, underscoring the existing challenges and limitations.

Clinical and molecular epidemiology of community-acquired, methicillin-resistant Staphylococcus aureus infections in children in central Greece.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in children have increased considerably in our area. In this study, we prospectively examined the epidemiological, clinical and molecular profile of CA-MRSA infections in children in central Greece. A total of 198 staphylococcal strains were isolated from patients with community-acquired infections over a 28-month period and 88 (44%) were found to be methicillin-resistant. Most patients with CA-MRSA had skin and soft-tissue infections (73%). Hospitalisation and surgery were more commonly required for patients with MRSA strains (p = 0.001 and p < 0.001, respectively). The presence of Panton-Valentine leukocidin (PVL) genes was identified in 28/41 (68%) CA-MRSA strains. All PVL(+) strains were found to carry a staphylococcal chromosomal cassette (SCC) mec element type IV and belonged to a single electrophoretic type similar to the European multi-locus sequence type 80 (ST80). The recent increase in CA-MRSA infections in children in our area is largely associated with the spread of the ST80 clone and their clinical characteristics are similar to those described in other parts of the world where different MRSA clones predominate.

Invasive meningococcal disease in children in Greece: comparison of serogroup A disease with disease caused by other serogroups.

Although invasive meningococcal disease caused by serogroup A is not prevalent in developed countries, a considerable number of cases were recently recorded in Greece. In this study, serogroup A meningococcal disease was compared prospectively with meningococcal disease caused by other serogroups, using similar settings of testing and management during a 5-year period between 1999 and 2003. The Neisseria meningitidis serogroup was determined in 262 cases. Serogroup B predominated, accounting for 158 (60%) of the cases. Serogroup A was second most frequent (19%), followed by serogroups W135 (11%), C (8%), and Y (2%). No cases due to serogroup C were recorded during the last year of the study. Patients with serogroup A disease were older and had a milder course compared to patients infected with serogroups B or C. Toxic appearance, purpura, thrombocytopenia, abnormal coagulation tests, and the need for admission to the intensive care unit, fluid resuscitation, inotropic drugs, and mechanical ventilation were less common. Although morbidity and mortality were lower in these patients, the differences were not significant. Serogroup B is predominant in our area, and the introduction of an effective vaccine against it is a priority. Serogroup A has emerged as the second most common serogroup, but the illness associated with it is milder.

Impact of influenza infection in healthy children examined as outpatients and their families.

Decisions regarding the introduction of influenza immunization in healthy children require an accurate evaluation of influenza disease burden not only in the inpatient but also in the outpatient setting. We prospectively examined the impact of virologically confirmed influenza in 1462 outpatient children (> or = 6 months to < 14 years) and their families, during two consecutive influenza seasons. Influenza was documented in 573/1462 (39%) outpatients with febrile respiratory illness and accounted for 13.5% of all outpatient visits during the 14 weeks of each season. Acute otitis media (AOM) was the most common complication (18.5%) and about 40% of influenza positive patients received antibiotics. AOM and antibiotic use were more common in children younger than 5 years of age who accounted for 58% of all patients. For each child sick with influenza a mean of 1.34 workdays were lost by the parents. Family members of influenza positive children were more likely to develop a secondary respiratory illness and to require medical visits and antibiotic prescriptions. Influenza is associated with a heavy morbidity burden in the community that may be reduced considerably with the implementation of immunization in children younger than 5 years of age.

Invasive meningococcal disease presenting as Henoch-Schonlein purpura.

Henoch-Schonlein purpura (HSP) is an acute systemic form of vasculitis that has been associated with a number of viral and bacterial infections. Described here are the cases of two children with invasive meningococcal disease who presented with clinical and laboratory findings typical of HSP. Meningococcal infection may have been the trigger for the manifestation of HSP in these patients.

Etiology of community-acquired pneumonia in hospitalized school-age children: evidence for high prevalence of viral infections.

BACKGROUND: Community-acquired pneumonia (CAP) in young children is most commonly associated with viral infections; however, the role of viruses in CAP of school-age children is still inconclusive. METHODS: Seventy-five school-age children hospitalized with CAP were prospectively evaluated for the presence of viral and bacterial pathogens. Nasopharyngeal washes were examined by polymerase chain reaction for viruses and atypical bacteria. Antibody assays to detect bacterial pathogens in acute-phase and convalescent-phase serum samples were also performed. RESULTS: A viral infection was identified in 65% of cases. Rhinovirus RNA was detected in 45% of patients; infection with another virus occurred in 31%. The most common bacterial pathogen was Mycoplasma pneumoniae, which was diagnosed in 35% of cases. Chlamydia pneumoniae DNA was not detected in any patient; results of serological tests were positive in only 2 patients (3%). Mixed infections were documented in 35% of patients, and the majority were a viral-bacterial combination. CONCLUSIONS: The high prevalence of viral and mixed viral-bacterial infections supports the notion that the presence of a virus, acting either as a direct or an indirect pathogen, may be the rule rather than the exception in the development of CAP in school-age children requiring hospitalization.

Epidemiology of respiratory syncytial virus bronchiolitis in hospitalized infants in Greece.

New therapies have been introduced for the prophylaxis and treatment of respiratory syncytial virus (RSV) infection in recent years. The aim of the study was to determine the epidemiological and clinical characteristics of infants hospitalized with bronchiolitis in our area. All patients under 1 year of age admitted with acute bronchiolitis during four consecutive RSV seasons from February 1, 1997 to June 30, 2000 were enrolled in the study. The records of patients admitted during the first season were reviewed retrospectively while the rest were followed prospectively. A total of 636 infants with bronchiolitis were admitted and RSV infection was documented in 61% of those tested. Admission to intensive care unit (ICU) was required for 6.2% of them and was more common in premature infants (26%) (p < 0.001). Case fatality rate was 0.7% (overall 0.3%). RSV bronchiolitis accounted for about 12% of all infant admissions during the 5 months of the yearly outbreak. Patients with documented RSV infection had a more severe illness with a higher ICU admission rate (6 vs. 1%, p = 0.008) and longer duration of hospitalization (mean 6.3 vs. 5.3 days, p < 0.001) compared to those who tested negative. Although none of the patients had a positive blood culture on admission a considerable number of them (210/636, 33%) were treated with antibiotics. RSV infection has a significant impact on infant morbidity in our settings which is more serious among those born prematurely. Documentation of RSV infection may be a marker of more severe illness in infants hospitalized with bronchiolitis. Antibiotic use has to be restricted since the occurrence of a serious bacteraemic illness on admission is a very rare event.

Epidemiology of invasive Haemophilus influenzae type b infections among children in Greece before the introduction of immunization.

We prospectively examined the epidemiology of invasive Haemophilus influenzae type b (Hib) infections among children under 5 y of age in the Greater Athens area before the introduction of immunization. The annual incidence of systemic Hib infections was 12/100000. Meningitis was the most common clinical entity and accounted for 69% of the cases. In the prevaccine era, the incidence of systemic Hib disease, particularly that of meningitis, was much lower in Greece compared to rates reported from Northern and Central Europe.