Vassiliki Syriopoulou

Multinational study of pneumococcal serotypes causing acute otitis media in children

Background. Streptococcus pneumoniae is a major cause of acute otitis media (AOM) in young children. More than 90 immunologically distinct pneumococcal serotypes have been identified, but limited information is available regarding their relative importance in AOM. Methods. We analyzed nine existing datasets comprising pneumococcal isolates from middle ear fluid samples collected from 1994 through 2000 from 3232 children with AOM from Finland, France, Greece, Israel, several East European countries, the US and Argentina. We examined the distribution of pneumococcal serotypes in relation to several demographic and epidemiologic variables, including gender, age, antibiotic resistance and source of culture material. Results. The major serotypes identified included 19F and 23F, each comprising 13 to 25% of pneumococcal middle ear fluid isolates in most datasets; 14 and 6B, comprising 6 to 18%; whereas 6A, 19A and 9V each comprised 5 to 10%. Despite differences in location, study design and antibiotic susceptibility, each major serotype was prominent in most age groups of each dataset. Serotypes represented in the 7-valent pneumococcal conjugate vaccine (PCV-7, 4, 6B, 9V, 14, 18C, 19F, 23F) accounted for 60 to 70% of all pneumococcal isolates in the 6- to 59-month age range, but only 40 to 50% of isolates in children <6 or ≥60 months old. Serotype 3 and, in certain datasets, serotypes 1 and 5, were more important in the <6- and ≥60-month age groups. In each age group vaccine-related serotypes (mainly 6A and 19A) comprised an additional 10 to 15% of all pneumococcal isolates. Four serotypes (23F, 19F, 14 and 6B) accounted for 83% of all penicillin-resistant observations. Conclusions. This analysis of several geographically diverse datasets indicates that a limited number of serotypes, largely represented in PCV-7, accounted for the majority of episodes of pneumococcal AOM in children between 6 and 59 months of age. Certain serotypes appeared to be relatively more significant in children <6 months or >59 months of age.

ASEPTIC MENINGITIS IN CHILDREN: ANALYSIS OF 506 CASES

Background Non-polio human enteroviruses are the leading cause of aseptic meningitis in children. The role of enterovirus PCR for diagnosis and management of aseptic meningitis has not been fully explored. Methodology/Principal Findings A retrospective study was conducted to determine the epidemiological, clinical, and laboratory characteristics of aseptic meningitis and to evaluate the role of enterovirus PCR for the diagnosis and management of this clinical entity. The medical records of children who had as discharge diagnosis aseptic or viral meningitis were reviewed. A total of 506 children, median age 5 years, were identified. The annual incidence rate was estimated to be 17/100,000 children less than 14 years of age. Most of the cases occurred during summer (38%) and autumn (24%). The dominant clinical symptoms were fever (98%), headache (94%) and vomiting (67%). Neck stiffness was noted in 60%, and irritation in 46% of the patients. The median number of CSF cell count was 201/mm3 with polymorphonuclear predominance (>50%) in 58.3% of the cases. Enterovirus RNA was detected in CSF in 47 of 96 (48.9%) children tested. Children with positive enterovirus PCR had shorter hospitalization stay as compared to children who had negative PCR or to children who were not tested (P = 0.01). There were no serious complications or deaths. Conclusions Enteroviruses accounted for approximately one half of cases of aseptic meningitis. PCR may reduce the length of hospitalization and plays important role in the diagnosis and management of children with aseptic meningitis.

Two Doses of a Lipid Formulation of Amphotericin B for the Treatment of Mediterranean Visceral Leishmaniasis

To evaluate the efficacy of a short course of a lipid formulation of amphotericin B (L-AmB) for the treatment of Mediterranean visceral leishmaniasis (VL), an open prospective study was conducted. Forty-one children with parasitologically confirmed leishmaniasis received L-AmB, 10 mg/kg daily for 2 days. The comparison groups were 30 children who, in a previous study, were treated with L-AmB, 4 mg/kg daily for 5 days, and 52 children who were treated with meglumine antimoniate. At 6 months after completion of treatment, overall treatment success was noted for 40 of 41 children treated with 2 doses of L-AmB, 27 of 30 children treated with 5 doses of L-AmB, and 47 of 52 children treated with meglumine antimoniate. Abatement of fever, reduction in spleen size, and correction of laboratory parameters occurred more quickly among the children who received 2 doses of L-AmB than among the comparison groups, and the total estimated cost of the 2-dose regimen was also lower than that of the other regimens. Two doses of L-AmB, 10 mg/kg each, is cost-effective therapy for Mediterranean VL in children.

Macrolide resistance in Streptococcus pyogenes: prevalence, resistance determinants, and emm types ☆ ☆☆

To investigate the antimicrobial resistance trends and the distribution of emm types of group A streptococci (GAS), we examined 1160 clinical isolates of GAS collected between 2003 and 2006. Susceptibilities to commonly used antimicrobial agents were determined by Etest, and macrolide resistance genes were detected by polymerase chain reaction (PCR). GAS isolates were typed by polymerase chain reaction PCR and sequencing of emm gene. The rates of resistance to erythromycin (ERY), clindamycin, azithromycin, tetracycline, and chloramphenicol were 14.9%, 1.4%, 14.9%, 18.9%, 0.6%, respectively. None of the isolates exhibited resistance to penicillin, ceftriaxone, linezolid, moxifloxacin, rifampicin, or vancomycin. Macrolide resistance increased from 12.1% in 2003 to 18.8% in 2006 (P = 0.02). Of 173 ERY-resistant GAS isolates, 93 (53.7%) harbored the mefA gene, 70 (40.4%) the ermA, and 10 (5.8%) the ermB. Eighty percent of the observed emm types are covered by the proposed 26-valent GAS vaccine. Among 173 ERY-resistant isolates, the predominant emm types were 12 (19.5%), 77 (17.9%), and 4 (16.8%), and among 770 ERY-susceptible isolates, the predominant types were 1 (18.8%), 12 (17.5%), 28 (13.8%). The observed antimicrobial resistance trends and the distribution of specific emm types have implications in guiding empiric therapy and in developing vaccine strategies to prevent GAS infections.

Mother to child transmission of hepatitis C virus: Rate of infection and risk factors

To determine the rate of mother-to-child transmission of hepatitis C virus (HCV) and identify risk factors associated with HCV transmission we prospectively studied 86 infants born to anti-HCV positive mothers. HCV infection was verified in all mothers before delivery and their HCV viral load was measured at or near delivery using reverse transcription polymerase reaction. For HCV genotyping the INNO-LiPA II probe assay was used. All mothers were tested for HIV infection. Possible risk factors for vertical transmission were recorded. The children were followed up for a minimum of 18 months for evidence of HCV infection, as determined by persistent HCV antibodies, or detection of HCV-RNA. Vertical transmission was restricted to infants born to viraemic mothers and the rate was 3.6% (95% CI 0.004–0.123). The HIV-infected mothers and those using drugs intravenously were more likely to transmit HCV to their children. The infected children had the same genotype as their mothers. Although the HCV RNA titre was higher in mothers who transmitted the virus than in those who did not, the viral load had borderline significance (p=0.08). Viral transmission was not influenced by mothers age, mode of delivery, genotype or type of feeding. Mother-to-child transmission of hepatitis C virus is uncommon and restricted to infants born to HCV viraemic mothers. Active drug use and HIV coinfection increase the risk for HCV vertical transmission.

Wilson disease in children: analysis of 57 cases.

Objectives: Wilson disease (WD) has a wide spectrum of clinical manifestations. Affected children may be entirely asymptomatic and the diagnosis problematic. Herein we present the clinical and laboratory characteristics of 57 children with WD and point out the diagnostic difficulties in a pediatric population. Patients and Methods: Clinical and laboratory data were collected from 57 consecutive children with WD. Evaluation included detailed physical examination, conventional laboratory testing, genetic analysis, and liver biopsy. Results: The mean age at diagnosis was 9.27 ± 3.62 years (range 4 months–18 years). Twenty patients were symptomatic, 19 were referred because of abnormal liver function test results and/or hepatomegaly, and 18 received their diagnoses after family screening. Twenty-two patients had both Kayser-Fleischer ring and decreased serum ceruloplasmin levels, 13 had urinary copper excretion after penicillamine challenge >1600 μg/24 hours, and 3 had liver copper content >250 μg/g dry weight. Of the remaining 19 patients, 17 had both low serum ceruloplasmin ≤20 mg/dL and increased urinary copper excretion, >75 μg/24 hours before, or >1000 μg/24 hours after penicillamine challenge. In 2 patients with equivocal cases who had serum ceruloplasmin 26 mg/dL, the diagnosis was confirmed by genetic analysis. No correlation was found between specific mutations and the disease phenotypic expression. Chelating therapy was well tolerated, and the outcome was satisfactory. Conclusions: WD in children may be obscure and requires extensive investigation to establish the diagnosis. Genetic analysis is needed in equivocal cases.

Epidemiology of invasive childhood pneumococcal infections in Greece.

A retrospective study was conducted to identify the epidemiologic characteristics of invasive pneumococcal infections among children <14y 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 Childrens 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/ 100000 children <14y of age, whereas the incidence rate for children <5y of age was 100/ 100000. 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.

Long-term follow-up of children with vesicoureteral reflux with and without antibiotic prophylaxis

The aim of the present study was to obtain data on the outcome of children with persistent vesicoureteral reflux (VUR) after cessation of antibiotic prophylaxis. Children with VUR who had been on antibiotic prophylaxis for at least 2 y and were free of urinary tract infections (UTI), had normal voiding patterns, and no hydronephrosis or new kidney scarring, had antibiotic prophylaxis discontinued, were followed up prospectively with urine cultures, voiding cystourethrography, and technecium-99m dimercaptosuccinate renal scintigraphy. The findings were compared with those of the same patients while they were on antibiotic prophylaxis. In 54 children (39 girls and 15 boys), antibiotic prophylaxis was discontinued. The mean follow-up time on and off antibiotic prophylaxis was 4.4±2.1 and 4.4±2.2 y, respectively. Nine UTI episodes occurred during the on- and 8 during the off-prophylaxis period. In 80 of 96 and in 68 of 74 ureters the reflux resolved or downgraded during the on- and off-prophylaxis periods, respectively. No new scar lesions were detected in any of the children. In conclusion, in children with persistent VUR and certain characteristics, antibiotic prophylaxis can be safely discontinued.

Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive infections and acute otitis media in children

A prospective study was conducted to determine the serotypes and antibiotic resistance patterns of pneumococcal isolates from children with invasive pneumococcal disease (IPD) and acute otitis media (AOM). From October 2001 to May 2002, 65 children with IPD (28 bacteraemic pneumonia, 24 bacteraemia without focus, 7 meningitis, 6 other infections) and 78 with AOM were identified. The most common serotypes causing IPD were 14 (32.3%), 6B (20.0%), 1 (18.5%) and 19F (7.7%) whereas the predominant serotypes causing AOM were 19F (35.9%), 14 (16.7%) and 23F (9.1%). Sixty-nine percent of IPD and 70.5% of AOM were caused by vaccine serotypes. The vaccine serotypes were more commonly encountered in meningitis cases and in children younger than 2 years of age. Intermediate resistance to penicillin was observed in 6 of 65 (9.2%) IPD isolates, one of which was intermediately resistant to cefotaxime (1.6%), whereas none exhibited high-level resistance to penicillin or other beta-lactam antibiotics. A higher proportion of antimicrobial resistance was noted in AOM isolates; 29 of 78 (37.4%) exhibited intermediate resistance and 8 (10.2%) high level resistance to penicillin, four of which had intermediate resistance to cefotaxime. Significant resistance was also noted to erythromycin; 38.5% of IPD and 48.7% of AOM isolates were resistant. Multidrug resistance was observed in one IPD and in eight AOM isolates. Conclusion:these findings have implications in the potential use of 7-valent conjugate vaccine in our region.

Febrile Seizures and Primary Human Herpesvirus 6 Infection

Primary human herpesvirus 6 infection is acquired mainly during the first two years of life and is often associated with febrile seizures. The aim of the present study was to investigate in Greece the frequency and clinical characteristics of primary human herpesvirus 6 (HHV-6) infection in hospitalized children with febrile seizures. Children aged from 6 months to 5 years without known neurologic disease were examined for primary HHV-6 infection, by real-time polymerase chain reaction in acute-phase plasma and by indirect immunofluorescent assay for antibody titers in acute and convalescent serum. Of 65 children included in the analysis, 55 experienced the first febrile episode of seizures and 10 the second. Primary HHV-6 infection was verified in 10 of 55 children with a first febrile episode (18%), whereas none of the 10 children with a second episode of seizures had primary HHV-6 infection. Eight children were infected with HHV-6 type B and two with type A. None of the 85 control subjects had primary HHV-6 infection, but 49% had immunoglobulin G antibodies against the virus. These findings suggest that primary HHV-6 infection is frequently associated with febrile seizures in children in this geographic region and should be considered, especially for a first episode of febrile seizures.