Emre Alhan

Vaccine for Prevention of Mild and Moderate-to-Severe Influenza in Children

BACKGROUND Commonly used trivalent vaccines contain one influenza B virus lineage and may be ineffective against viruses of the other B lineage. We evaluated the efficacy of a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages. METHODS In this multinational, phase 3, observer-blinded study, we randomly assigned children 3 to 8 years of age, in a 1:1 ratio, to receive the QIV or a hepatitis A vaccine (control). The primary end point was influenza A or B confirmed by real-time polymerase chain reaction (rt-PCR). Secondary end points were rt-PCR-confirmed, moderate-to-severe influenza and rt-PCR-positive, culture-confirmed influenza. The vaccine efficacy and the effect of vaccination on daily activities and utilization of health care resources were assessed in the total vaccinated cohort (2584 children in each group) and the per-protocol cohort (2379 children in the QIV group and 2398 in the control group). RESULTS In the total vaccinated cohort, 62 children in the QIV group (2.40%) and 148 in the control group (5.73%) had rt-PCR-confirmed influenza, representing a QIV efficacy of 59.3% (95% confidence interval [CI], 45.2 to 69.7), with efficacy against culture-confirmed influenza of 59.1% (97.5% CI, 41.2 to 71.5). For moderate-to-severe rt-PCR-confirmed influenza, the attack rate was 0.62% (16 cases) in the QIV group and 2.36% (61 cases) in the control group, representing a QIV efficacy of 74.2% (97.5% CI, 51.5 to 86.2). In the per-protocol cohort, the QIV efficacy was 55.4% (95% CI, 39.1 to 67.3), and the efficacy against culture-confirmed influenza 55.9% (97.5% CI, 35.4 to 69.9); the efficacy among children with moderate-to-severe influenza was 73.1% (97.5% CI, 47.1 to 86.3). The QIV was associated with reduced risks of a body temperature above 39°C and lower respiratory tract illness, as compared with the control vaccine, in the per-protocol cohort (relative risk, 0.29 [95% CI, 0.16 to 0.56] and 0.20 [95% CI, 0.04 to 0.92], respectively). The QIV was immunogenic against all four strains. Serious adverse events occurred in 36 children in the QIV group (1.4%) and in 24 children in the control group (0.9%). CONCLUSIONS The QIV was efficacious in preventing influenza in children. (Funded by GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT01218308.).

A prospective study of etiology of childhood acute bacterial meningitis, Turkey.

Vaccines to prevent bacterial meningitis in this region must provide reliable protection against serogroup W-135.

Inappropriate antimicrobial use in Turkish pediatric hospitals: A multicenter point prevalence survey

OBJECTIVES Although well-defined principles of rational antimicrobial use are available, inappropriate prescribing patterns are reported worldwide. Accurate information on the usage of antimicrobials, including factors associated with and influencing their use, is valuable for improving the quality of prescription practices. METHODS In this cross-sectional point prevalence survey, data on patients hospitalized in 12 different childrens hospitals were collected on a single day. Appropriateness of prescription was compared between the types of antimicrobials prescribed, indications, wards, and presence of/consultation with an infectious disease physician (IDP). RESULTS A total 711 of 1302 (54.6%) patients evaluated were receiving one or more antimicrobial drugs. The antimicrobial prescription rate was highest in pediatric intensive care (75.7%) and lowest in the surgery wards (37.0%). Of the 711 patients receiving antimicrobials, 332 patients (46.7%) were found to be receiving at least one inappropriately prescribed drug. Inappropriate use was most frequent in surgery wards (80.2%), while it was less common in oncology wards (31.8%; p<0.001). Respiratory tract infection was the most common indication for antimicrobial use (29.4%). Inappropriate use was more common in deep-seated infections (54.7%) and respiratory infections (56.5%). Fluoroquinolones were used inappropriately more than any other drugs (81.8%, p=0.021). Consultation with an IDP appears to increase appropriate antimicrobial use (p=0.008). CONCLUSIONS Inappropriate antimicrobial use remains a common problem in Turkish pediatric hospitals. Consultation with an IDP and prescribing antimicrobial drugs according to microbiological test results could decrease the inappropriate use of antimicrobials.

Cerebrospinal Fluid Shunt Infections in Children

Infections of cerebrospinal fluid shunts continue to be a substantial source of mortality and morbidity in children with hydrocephalus. Although several therapeutic modalities are currently used for the treatment of shunt infections, there are no clear guidelines for treatment. The purpose of this study was to determine the common pathogens of cerebrospinal fluid shunt infections and evaluate the success of our management. Thirty-five children treated for ventriculoperitoneal shunt infections over the past 9 years were reviewed. The management protocol consisted of the removal of the infected shunt, the application of ventricular taps or reservoir placement, intraventricular antibiotic treatment, and the placement of a new shunt when cerebrospinal fluid sterility was achieved. Four patients were treated with antibiotics alone. Most episodes occurred within 4 months of shunt placement. The most common causative microorganism identified was Staphylococcus epidermidis, followed by S. aureus, and S. warneri. Three patients died from complications of shunt infections, 2 patients had a recurrent shunt infection, while the remaining 29 patients remained free from shunt-related complications. In agreement with the evidence published in the literature, our findings suggest that the above management protocol is effective for the treatment of cerebrospinal fluid shunt infections.

Multicenter Prospective Study on the Burden of Rotavirus Gastroenteritis in Turkey, 2005–2006: A Hospital-Based Study

Rotavirus is the main cause of gastroenteritis and dehydration requiring hospitalization among infants and children. Despite the high diarrhea-related mortality rate, there are limited studies describing the prevalence of rotavirus in Turkey. The disease burden of rotavirus gastroenteritis in Turkey was assessed by active, prospective surveillance conducted in accordance with a modified World Health Organization generic protocol from 1 June 2005 through 1 June 2006. A total of 411 children aged <5 years who were hospitalized for gastroenteritis in 4 centers were enrolled. Rotavirus was identified in 53% of samples from the 338 children tested; the range for individual centers was 32.4%-67.4%. Overall, 83.8% of rotavirus-positive children were aged <2 years. Rotavirus gastroenteritis occurred year-round but peaked in the winter. G1P[8] was the most widely prevalent strain (76% of strains), followed by G2P[4] (12.8%). G9P[8] was reported in samples from 3.9% of children. These data support the need for a rotavirus vaccine in Turkey.

Serotype distribution and antibiotic susceptibility of invasive Streptococcus pneumoniae disease isolates from children in Turkey, 2001–2004

Streptococcus pneumoniae is a major cause of childhood invasive infections, including sepsis, pneumonia and meningitis, and of non-invasive disease such as otitis media. Most S. pneumoniae strains from invasive infections capable of creating treatment problems in children because of antibiotic resistance belong to serogroups 14, 6, 9, 19 and 23. Despite progress in antimicrobial therapy, effective treatment is becoming increasingly complicated because of the rising worldwide emergence of pneumococci resistant to penicillin G and other commonly used antimicrobial agents [1, 3, 5].The aim of the present study was to investigate the antibiotic susceptibility pattern and serotype distribution of S. pneumoniae isolates from children younger than 10 years of age hospitalized with invasive pneumococcal disease (IPD) in Turkey during the years 2001–2004. All patients admitted and treated for invasive infections attributable to S. pneumoniae, between November 2001 and April 2004, in the six large university hospitals in Turkey, located in Istanbul, Adana, Ankara and Izmir, were included in this study. The study cohort represents roughly 30% (20 million) of the population of Turkey. Cases were eligible for evaluation if S. pneumonia, isolated from a normally sterile body site, was identified on the basis of typical colony morphology on blood agar as well as Gram strain, optochin sensitivity and bile solubility tests. Isolate identity was confirmed at the central study laboratory (Department of Microbiology and Infection Disease, Istanbul Faculty of Medicine). Susceptibility tests to antimicrobial agents (penicillin G, amoxicillin-clavulanic acid, cefotaxime, erythromycin and trimethoprim-sulfamethoxazole) were performed by standard disc diffusion method on Müller Hinton agar supplemented with 5% sheep blood. The susceptibility for penicillin was detected with a 1-μl oxacillin disc. The minimal inhibitory concentration (MIC) of the antibiotics was determined by the E test. Disc diffusion tests were employed according to the Clinical and Laboratory Standards Institute guidelines (formerly known as the NCCLS guidelines). An inoculum density equivalent to 0.5 MacFarland standard was prepared in Muller Hinton broth. Capsular typing was carried out by the Quellung reaction, using group and factor sera provided by the Statens Serum Institute (Denmark). Vaccine-type strains included serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. We defined vaccine-related strains as pneumococci with serotypes within the same serogroup as the vaccine types (i.e. serotypes 6A, 9A, 9L, 9N, 18A, 18B, 18F, 19A, 19B, 19C, 23A and 23B) [6]. I. Yalçın Department of Paediatrics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

Cerebral salt wasting in tuberculous meningitis: treatment with fludrocortisone.

Abstract Three cases of cerebral salt wasting complicating tuberculous meningitis are described. Diagnosis was based on hyponatraemia associated with high urinary sodium excretion and inappropriately high urine output in the presence of dehydration. Treatment with fludrocortisone resulted in sodium and fluid homeostasis.

Clinical features of Bardet-Biedl syndrome

Six patients with Bardet‐Biedl syndrome who have been followed in our clinics for the last 5 years are reported in this study. Of the five classic features of this syndrome; obesity and mental retardation were present in all cases, retinal disturbances were present in five, Polydactyly in three and hypogenitalism was observed in all four male patients. Renal involvement, often suggested as a cardinal feature of this syndrome, was described in two patients. Iron deficiency anemia occurred in three patients, two patients were of short stature, one patient presented with an empty sella, and in two patients clinodactyly was detected. The results are compared to previously published literature and discussed.

Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005–2012 in Turkey: A multicenter prospective surveillance study

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤ 18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.

Hepatitis B and C virus infections in Turkish children with cancer

In this study, we tested 137 Turkish children with cancer (51 with acute leukemia, 48 with lymphoma, 38 with solid tumors) while they were undergoing chemotherapy, and a control group of 45 for evidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections using the enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). The control group included children with other disease who had applied to the outpatient clinic during the study period and had no history of jaundice or transfusion. Sixty-five (47.4%) patients with cancer and 7 (20%) children in the control group were positive for hepatitis B surface antigen (HBsAg) (p < 0.01). HBV DNA was detected in 59 (43.1%) patients and in 9 (20%) controls (p < 0.01). HCV specific antibody (anti-HCV) was detected in 8 (5.8%) patients and in 1 (2.2%) control (p > 0.05). Eight patients (5.8%) had circulating HCV RNA, but none had in the control group (p = 0.09). Ten (13.9%) of the 72 patients who were negative for HBsAg had circulating HBV DNA, and 7 (5.4%) of the 129 patients who were negative for anti-HCV had circulating HCV RNA. We concluded that HBV and HCV infections are common among Turkish children with cancer. In countries where HBV infection is widespread among the general population as in Turkey, children with cancer are under greater risk for HBV infection.