An evaluation of a Stenotrophomonas maltophilia outbreak due to commercial arterial blood gas collection kit.

BACKGROUND: Stenotrophomonas maltophilia is a gram-negative bacterium that can cause hospital infections and outbreaks within hospitals. This study aimed to evaluate an outbreak of Stenotrophomonas maltophilia, caused by ready-to-use commercial syringes containing liquid lithium and heparin for arterial blood gas collection in a university hospital. METHODS: Upon detecting an increase in Stenotrophomonas maltophilia growth in blood cultures between 15.09.2021 and 19.11.2021, an outbreak analysis and a case-control study (52 patients for the case group, 56 patients for the control group) were performed considering risk factors for bacteremia. Samples from possible foci for bacteremia were also cultured. Growing bacteria were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The genetic linkage and clonal relationship isolates were investigated with pulsed-field gel electrophoresis (PFGE) in the reference laboratory. RESULTS: In the case-control study, the odds ratio for the central venous catheter [3.38 (95% confidence interval [CI]: 1.444, 8.705 ; p = 0.006)], for surgery [3.387 (95% confidence interval [CI]: 1.370, 8.373 ; p = 0.008)] and for arterial blood gas collection history [18.584 (95% confidence interval [CI]:4.086, 84.197; p < 0.001)] were identified as significant risk factors. Stenotrophomonas maltophilia growth was found in ready-to-use commercial syringes used for arterial blood gas collection. Molecular analysis showed that the growths in the samples taken from commercial syringes and the growths from blood cultures were the same. It was decided that the epidemic occurred because the method for sterilization of heparinized liquid preparations were not suitable. After discontinuing the use of the kits with this lot number, the outbreak was brought under control. CONCLUSIONS: According to our results, disposable or sterile medical equipment should be included as a risk factor in outbreak analyses. The method by which injectors containing liquids, such as heparin, are sterilized should be reviewed. Our study also revealed the importance of the cooperation of the infection control team with the microbiology laboratory.

A comparison of chlorhexidine and povidone-iodine solutions in neonatal intensive care units.

BACKGROUND: Povidone-iodine (10%; PI) and 2% chlorhexidine in 70% isopropyl alcohol (CHG-IA) solutions are among the most widely used disinfectants in the neonatal intensive care units. This study compares the use of these disinfectants and helps decide which is superior to the other for neonatal use. METHODS: All term and preterm infants born and hospitalized in Bursa Uludag University Hospital between July 2018-March 2020 were included. The infants were randomized into two disinfectant groups before birth. The application site was cleaned with the assigned disinfectant before intervention. The infants were screened for rates of neonatal sepsis, thyroid-stimulating hormone (TSH) levels, free thyroxine (fT4) levels, skin reactions to the assigned solution, and acute neurological side effects. RESULTS: We enrolled 208 term and preterm infants (PI:104 vs. CHG-IA: 104) in the study. The prematurity rates were identical (PI: 74.0%; CHG-IA: 72.1%; p = 0.755). Neonatal sepsis rates among these groups were not statistically different (PI: 8.7%; CHG-IA: 4.8%; p = 0.406). The median TSH value of the PI group was high (4.05 mIU/L) in comparison with that of the CHG-IA group (3.09 mIU/L; p = 0.016). No cutaneous or neurological side effects were recorded in patients treated with CHG-IA solution. CONCLUSIONS: Although these two solutions were equally protective against infections, the CHG-IA solution was a better alternative to PI for neonatal use. Considering that the PI solution may be responsible for impaired thyroid function, the CHG-IA solution is a good alternative because it provides sufficient protection with a safer adverse effect profile.

The Evaluation of Central Venous Catheter-related Complications in Pediatric Acute Leukemia Patients: Single Center Experience.

Central venous catheters (CVCs) are important for maintenance of childhood leukemia treatment but CVCs may develop complications. The aim of this study was to retrospectively evaluate the CVC-related complication rate, complication types, and outcome in children with acute leukemia. Complications developing in 310 CVCs (ports n=250, Hickman catheters n=60) inserted in 262 patients were evaluated. A total of 225,296 catheter days were screened. Median (range) CVC in-dwelling time was 661.5 (1 to 2636) days. In total, 157 complications developed of which 91 (58%) were infectious complications, 35 (22.3%) were vascular, 19 (12.1%) were surgical, and 12 (7.6%) were mechanical. Hickman catheters had a higher complication rate and were more prone to mechanical complications ( P <0.01) but there was no difference for other complications. A lower absolute neutrophil count at insertion was observed in children with infectious complications ( P <0.01). Seventy-eight of 136 catheters (57.3%) had to be removed prematurely. The overall complication rate was 0.65 per 1000 catheter days. In multivariate analysis, relapse leukemia, Hickman catheter and low absolute neutrophil count increased complication risk by 4.00, 1.97, and 1.92 times, respectively. Five (1.9%) deaths occurred because of catheter complications. Safe use of CVCs can be improved by early detection of complications and an experienced catheter care team.

An outbreak of Ralstonia insidiosa bloodstream infections caused by contaminated heparinized syringes.

INTRODUCTION: Ralstonia insidiosa, a gram-negative waterborne bacteria able to survive and grow in any type of water source, can cause nosocomial infections, and are considered emerging pathogens of infectious diseases in hospital settings. In this study, we report an outbreak of R. insidiosa at our center related to contaminated heparinized syringes. MATERIAL AND METHODS: The present study was conducted in a tertiary care university hospital in Turkey. An outbreak analysis was performed between September 2021 and December 2021. Microbiological samples were obtained from environmental sources and from patient blood cultures. Species identification was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). To investigate the clonality of strains, all confirmed isolates were sent to the National Reference Laboratory and pulsed-field gel electrophoresis (PFGE) was used to perform molecular typing. RESULTS: Seventeen R. insidiosa isolates were identified from the blood cultures of 13 patients from various wards and intensive care units. Isolates from seven patient blood cultures and two heparinized blood gas syringes were characterized by PFGE. All isolates were found to belong to the same clone of R. insidiosa. CONCLUSION: R. insidiosa was identified as the cause of a nosocomial infection outbreak in our hospital, which was then rapidly controlled by the infection-control team. When rare waterborne microorganisms grow in blood or other body fluid cultures, clinicians and the infection-control team should be made aware of a possible outbreak.

Comparison of SARS-CoV-2 Antibodies and Six Immunoassays in Pediatric and Adult Patients 12 Weeks After COVID-19.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral immune persistence has been proposed to be affected by patients' characteristics. Moreover, available conflicting assay results are needed to be settled through comparative research with defined clinical specimens. Methods This prospective study investigated SARS-CoV-2-specific antibodies among 43 adults and 34 children at a mean of 12 weeks after the onset of COVID-19 symptoms using six serological assays and compared their performance. We used two Euroimmun (Euroimmun, Luebeck, Germany), two automated Roche Elecsys (Basel, Switzerland), and two rapid immuno-chromatographic Ecotest (Matrix Diagnostics, Assure Tech. (Hangzhou) Co., L, China) assays to investigate SARS-CoV-2 antibodies. Results The findings showed that the Roche Elecsys anti-S total test yielded the best positivity/sensitivity (children 94.1% and adults 93.0%; p = 0.877) while five immunoglobulin IgG targeting assays had similar positivity/sensitivity between children (88.2% to 94.1%) and adults (88.4% to 93.0%) (p > 0.05). Although IgM positivity was relatively low (p < 0.001), it was found in the majority of our pediatric and adult patients (67.6% and 86.0%, respectively; p = 0.098). SARS-CoV-2 S IgG titers were found to be higher among males in pediatric and adult groups compared to females (p = 0.027 and p = 0.041, respectively). Furthermore, we observed significantly higher antibody titers among pneumonia patients (p = 0.001). Conclusion Overall, we concluded SARS-CoV-2 antibody persistence over an average of 12 weeks after the onset of COVID-19 symptoms. While automated Roche Elecsys total antibody assays yielded the best sensitivity (> 90%) and five assays targeting IgG had acceptable performance. Patients with pneumonia and males have higher antibody titers. The effect of antibody persistence on re-infections should be monitored in longitudinal studies.

Prevalence of Anosmia in 10.157 Pediatric COVID-19 Cases: Multicenter Study from Turkey.

INTRODUCTION: COVID-19-related anosmia is a remarkable and disease-specific finding. With this multicenter cohort study, we aimed to determine the prevalence of anosmia in pediatric cases with COVID-19 from Turkey and make an objective assessment with a smell awareness questionnaire. MATERIAL AND METHODS: This multicenter prospective cohort study was conducted with pediatric infection clinics in 37 centers in 19 different cities of Turkey between October 2020 and March 2021. The symptoms of 10.157 COVID-19 cases 10-18 years old were examined. Age, gender, other accompanying symptoms, and clinical severity of the disease of cases with anosmia and ageusia included in the study were recorded. The cases were interviewed for the smell awareness questionnaire at admission and one month after the illness. RESULTS: Anosmia was present in 12.5% (1.266/10.157) of COVID-19 cases 10-18 years of age. The complete records of 1053 patients followed during the study period were analyzed. The most common symptoms accompanying symptoms with anosmia were ageusia in 885 (84%) cases, fatigue in 534 cases (50.7%), and cough in 466 cases (44.3%). Anosmia was recorded as the only symptom in 84 (8%) of the cases. One month later, it was determined that anosmia persisted in 88 (8.4%) cases. In the smell awareness questionnaire, the score at admission was higher than the score one month later (P < 0.001). DISCUSSION: With this study, we have provided the examination of a large case series across Turkey. Anosmia and ageusia are specific symptoms seen in cases of COVID-19. With the detection of these symptoms, it should be aimed to isolate COVID-19 cases in the early period and reduce the spread of the infection. Such studies are important because the course of COVID-19 in children differs from adults and there is limited data on the prevalence of anosmia.

Nine-month course of SARS-CoV-2 antibodies in individuals with COVID-19 infection.

BACKGROUND: The continual course of the pandemic points to the importance of studies on the rate and durability of protective immunity after infection or vaccination. AIMS: In this study, we aimed to monitor anti-nucleocapsid (N) and anti-spike (S) antibodies against SARS-CoV-2 nearly 9 months duration after infection. METHODS: Anti-nucleocapsid (N) (at 11-15-20-29-38 weeks) and anti-spike antibodies (at 11 and 38 weeks) against SARS-CoV-2 were monitored during 38 weeks after the initial symptoms of COVID-19. RESULTS: Of 37 cases between 18 and 57 years old, 54% were women. The findings showed that anti-N antibodies decreased significantly after the 15th week (between 15 and 20 weeks, p = 0.016; 20-29 weeks, p = 0.0009; and 29-38 weeks, p = 0.049). At the 38th week, mean antibody levels decreased 35% compared to the 11th week, and 8% of the cases turned negative results. Anti-N antibody average level was 56.48 on the 11th week (the cut-off index threshold ≥ 1). It was estimated statistically that it would decrease to an average of 20.48 in weeks 53-62. In females, average antibody levels of all measurements were lower than males (p > 0.05). Anti-S antibody levels 14% increased at 38th week compared to 11th week (quantitative positivity threshold ≥ 0.8 U/ml), and no cases were negative at 38th week. CONCLUSIONS: Patients had ≥ 90% positivity after at least 9 months of symptoms, both anti-N and anti-S antibodies. In all samples, both anti-N and anti-S antibody levels were lower in females. The findings suggest that the quantitative values of anti-S antibodies remained high for at least 9 months and could provide protection.

Invasive Fungal Infections in Children with Leukemia: Clinical Features and Prognosis

Objective: The incidence of invasive fungal infections (IFIs) has increased due to intensive chemotherapy in childhood leukemia. The aim of this study was to evaluate the incidence, risk factors, causative pathogens, and impact on survival of IFIs among pediatric leukemia patients. Materials and Methods: The hospital records of 307 children with acute lymphoblastic leukemia (ALL, n=238), acute myeloid leukemia (AML, n=51), and relapsed leukemia (n=18) between January 2010 and December 2015 were retrospectively evaluated. Results: A total of 1213 febrile neutropenia episodes were recorded and 127 (10.4%) of them were related to an IFI. Of 307 children, 121 (39.4%) developed IFIs. The mean age was significantly older in the IFI group compared to children without IFIs (p<0.001). IFIs were defined as possible, probable, and proven in 73.2%, 11.9%, and 14.9% of the attacks, respectively. Invasive aspergillosis (81.9%) was the most frequent infection, followed by invasive candidiasis (13.4%) and rare fungal diseases (4.8%). The majority of IFI attacks in both ALL and AML occurred during the induction phase. In total, the death rate was 24% and the IFI-related mortality rate was 18%. The mortality rate among children with IFIs was found to be significantly higher than that of children without IFIs (p<0.001). Overall and event-free survival rates at 5 years were also found to be significantly lower in the IFI group (p<0.001). Relapse (odds ratio: 8.49) was the most effective risk factor for mortality, followed by developing an IFI episode (odds ratio: 3.2) and AML (odds ratio: 2.33) according to multivariate regression analysis. Conclusion: Our data showed that IFIs were more common in older children. Although proven and probable IFI episodes were more frequently diagnosed in cases of relapse and AML, children with ALL and AML had similar frequencies of experiencing at least one episode Conclusion: Our data showed that IFIs were more common in older children. Although proven and probable IFI episodes were more frequently diagnosed in cases of relapse and AML, children with ALL and AML had similar frequencies of experiencing at least one episode

Nasopharyngeal Meningococcal Carriage among Children and Adolescents in Turkey in 2018: An Unexpected High Serogroup X Carriage.

Meningococcal carriage studies and transmission modeling can predict IMD epidemiology and used to define invasive meningococcal disease (IMD) control strategies. In this multicenter study, we aimed to evaluate the prevalence of nasopharyngeal Neisseria meningitidis (Nm) carriage, serogroup distribution, and related risk factors in Turkey. Nasopharyngeal samples were collected from a total of 1267 children and adolescents and were tested with rt-PCR. Nm carriage was detected in 96 participants (7.5%, 95% CI 6.1-9.0), with the peak age at 13 years (12.5%). Regarding age groups, Nm carriage rate was 7% in the 0-5 age group, was 6.9%in the 6-10 age group, was 7.9% in the 11-14 age group, and was 9.3% in the 15-18 age group. There was no statistically significant difference between the groups (p > 0.05). The serogroup distribution was as follows: 25% MenX, 9.4% MenA, 9.4% MenB, 2.1% MenC, 3.1% MenW, 2.1% for MenY, and 48.9% for non-groupable. The Nm carriage rate was higher in children with previous upper respiratory tract infections and with a high number of household members, whereas it was lower in children with antibiotic use in the last month (p < 0.05 for all). In this study, MenX is the predominant carriage strain. The geographical distribution of Nm strains varies, but serogroup distribution in the same country might change in a matter of years. Adequate surveillance and/or a proper carriage study is paramount for accurate/dynamic serogroup distribution and the impact of the proposed vaccination.

Changing epidemiology of influenza and other respiratory viruses in the first year of COVID-19 pandemic.

INTRODUCTION: We aimed to determine the epidemiological change in influenza and other respiratory tract viruses isolated from patients with nasopharyngeal swab samples in our hospital during the COVID-19 period. METHODS: We investigated nasopharyngeal swabs for respiratory viruses between March 2020 and February 2021 during the first year of pandemic in Turkey. We used QIAStat Dx Respiratory panel (Qiagen, Germany) in QIAStat Dx (Qiagen, Germany) for detection of respiratory viruses between March 2020 and February 2021. Respiratory panel kit included influenza A, B, influenza A H1N1, rhinovirus/enterovirus, parainfluenza (PIV) 1,2,3,4, coronaviruses (CoVs) NL 63, 229E, OC43 and HKU1, human metapneumovirus (MPV) A/B, bocavirus, respiratory syncytial virus (RSV) A/B and adenovirus. RESULTS: We retrospectively analyzed the results of 319 nasopharyngeal swab samples. The average age of 199 (62.4%) male and 120 (37.6%) female patients between the ages of 0-92 was 16 years. We found that 101 (31.7%) samples were positive for viruses. Rhino/enteroviruses were the most common viruses in all age groups. Influenza positivity rate during the first year of pandemic declined to 2.3% from 17.3% among the previous year. MPV infection activity did not change during the pandemic. DISCUSSION: According to our findings we argue that epidemiology of respiratory viruses has changed during the pandemic period. Despite the current clinical focus on the COVID-19 pandemic, clinicians should keep in mind that rhino/enterovirus and MPV infections may mimic COVID-19 and respiratory infections should be differentially diagnosed with rapid multiplex kits containing SARS-CoV-2, rhino/enterovirus and MPV.

Epidemiological, Clinical, and Laboratory Features of Children With COVID-19 in Turkey.

Objectives: The aim of this study is to identify the epidemiological, clinical, and laboratory features of coronavirus disease 2019 (COVID-19) in children. Methods: A retrospective study was conducted by pediatric infectious disease specialists from 32 different hospitals from all over Turkey by case record forms. Pediatric cases who were diagnosed as COVID-19 between March 16, 2020, and June 15, 2020 were included. Case characteristics including age, sex, dates of disease onset and diagnosis, family, and contact information were recorded. Clinical data, including the duration and severity of symptoms, were also collected. Laboratory parameters like biochemical tests and complete blood count, chest X-ray, and chest computed tomography (CT) were determined. Results: There were 1,156 confirmed pediatric COVID-19 cases. In total, male cases constituted 50.3% (n = 582) and females constituted 49.7% (n = 574). The median age of the confirmed cases was 10.75 years (4.5-14.6). Of the total cases, 90 were younger than 1 year of age (7.8%), 108 were 1-3 years of age (9.3%), 148 were 3-6 years of age (12.8%), 298 were 6-12 years of age (25.8%), 233 were 12-15 years of age (20.2%), and 268 cases were older than 15 years of age (23.2%). The most common symptom of the patients at the first visit was fever (50.4%) (n = 583) for a median of 2 days (IQR: 1-3 days). Fever was median at 38.4°C (38.0-38.7°C). The second most common symptom was cough (n = 543, 46.9%). The other common symptoms were sore throat (n = 143, 12.4%), myalgia (n = 141, 12.2%), dyspnea (n = 118, 10.2%), diarrhea (n = 112, 9.7%), stomachache (n = 71, 6.1%), and nasal discharge (n = 63, 5.4%). When patients were classified according to disease severity, 263 (22.7%) patients were asymptomatic, 668 (57.7%) patients had mild disease, 209 (18.1%) had moderate disease, and 16 (1.5%) cases had severe disease. One hundred and forty-nine (12.9%) cases had underlying diseases among the total cases; 56% of the patients who had severe disease had an underlying condition (p < 0.01). The need for hospitalization did not differ between patients who had an underlying condition and those who do not have (p = 0.38), but the need for intensive care was higher in patients who had an underlying condition (p < 0.01). Forty-seven (31.5%) of the cases having underlying conditions had asthma or lung disease (38 of them had asthma). Conclusions: To the best of our knowledge, this is one of the largest pediatric data about confirmed COVID-19 cases. Children from all ages appear to be susceptible to COVID-19, and there is a significant difference in symptomatology and laboratory findings by means of age distribution.

Risk Factors for Respiratory Syncytial Virus Infections in Moderate/Late Premature Infants in Turkey: A Prospective Multicenter Epidemiological Study.

OBJECTIVE: Respiratory syncytial virus (RSV) is one of the most prevalent causes of lower respiratory tract infection (LRTI). The primary objective of this study is to provide the risk modelling of confirmed RSV infection in children who were born preterm at 29 to 35 weeks of gestational age and presented with LRTI. STUDY DESIGN: This prospective, multicenter study was performed between October 2015 and March 2017. Premature infants born with gestational age between 29 and 35 weeks that were ≤2 years of age at the beginning of the RSV season and admitted to the hospital with clinical findings of LRTI during the season were included. RSV-positive and -negative infants were compared in terms of demographic features, risk factors, and requirement of hospitalization. RESULTS: RSV positive group was lower than RSV negative group and ratio of ≤3 months age at admission was significant higher in RSV (+) group. RSV-positive infants were found to be significantly born during or 3 months prior to RSV season. The rate and duration of hospitalization and need for mechanical ventilation were significantly higher in RSV positive infants. The rate and duration of hospitalization in RSV positive patients was related to the chronological age. CONCLUSION: This study showed that preterm infants with RSV-associated LRTI significantly needed more hospitalization, intensive care admission, and mechanical ventilation. In addition need of hospitalization and duration of hospitalization were significant higher in ≤3 months of age. Therefore, we suggest the importance of palivizumab prophylaxis in infants ≤ 3 months chronological age, especially during the RSV season.

[Evaluation of Micafungin Use in Children]. / Çocuklarda Mikafungin Kullaniminin Degerlendirilmesi.

Micafungin is recommended especially in patients with liver and kidney failure and in the presence of other side effects due to antifungals apart from its known priority indications such as invasive candidiasis. The aim of this study was to evaluate the children who have received micafungin treatment. In the study, 125 children who were hospitalized in the pediatric wards and intensive care units of our hospital and had used micafungin between November 2016 and January 2019 were analyzed retrospectively. Clinical data, micafungin indication, blood values on the first and fourth days of the treatment, side effects of the drug and efficacy were evaluated. Sixty percent (75/125) of the patients were male and the mean age of all the patients were 58 ± 67 (0-215, 30) months. Approximately half of the cases (48%) had malignancy and 13% of them were premature. Sixty-two percent (n= 37) of the malignencies were hematological (27 acute lymphocytic leukemia, nine acute myeloid leukemia, one myelodysplastic syndrome) and 38% (n= 23) were oncological (six neuroblastoma, four Hodgkin lymphoma, two Non-Hodgkin's lymphoma, five sarcomas, one hepatoblastoma, five others) malignencies. The major cause of hospitalization was sepsis (53%). The patients had several risk factors like immunosuppressive therapy (n= 68, 54%), neutropenia (n= 61, 49%), central venous catheter (n= 102, 82%), nasogastric tube (n= 63, 50%), endotracheal intubation tube (n= 49, 39%), urinary catheter (n= 14, 11%) and total parenteral nutrition (n= 81, 65%). Thirteen percent (n= 16) of the cases were post-operative patients. Candida species were cultivated in 97 clinical specimens (blood, endotracheal aspirate, sputum, urine, etc.) among 23 (18%) of the patients. Thirteen (10%) of the patients had candidemia and 62% of them were non-albicans strains. In all candidemias, strains were echinocandin susceptible, and blood cultures were negative within four days. When all the patients (n= 125) were evaluated, a significant decrease in C-reactive protein, an increase in sodium, and a decrease in alanine aminotransferase were observed on the fourth day of micafungin treatment (p<0.05). A total of 39 (31%) patients underwent various antifungal treatments for median seven (1-60) days prior to micafungin treatment. Fourteen (36%) of these 39 patients, had elevated liver function tests (LFT), 10 (26%) of them had hypokalemia, and five (13%) of them had elevated renal function tests. Ten (26%) patients had antifungal-induced hypokalemia previously; and potassium levels were normalized after micafungin treatment (p= 0.0001). The patients for which micafungin treatment was chosen due to elevated liver function tests (n= 47, 38%), whether the antifungalinduced or not; alanine aminotransferase and aspartate aminotransferase levels were decreased after micafungin treatment (p= 0.0001 and p= 0.0001, respectively). Nineteen (15%) of the patients have died within the first 30 days of micafungin treatment and one of them had candidemia. No micafungin treatment related significant side effects were observed in any of the patients. Our study showed that micafungin could be a safe and effective option in pediatric cases including newborns with high liver and kidney function tests.

COVID-19 and re-opening of schools: Opinions with scientific evidence.

Due to the COVID-19 pandemic, more than 90% of students worldwide were affected by education loss. Moreover, for school-age children and adolescents, there may be worsening of nutrition, increasing mental health disorders, lack of physical activity, and related deleterious consequences raise concerns about negative habits, child violence, and abuse. Face-to-face education in schools provides positive educational opportunities that cannot be achieved with online education. In studies from various countries, children have milder disease, constituting as little as 1-8% of all laboratory-confirmed COVID-19 cases, with less transmission capacity to household contacts than adults (0.5-7% vs. 10-20%). Symptomatic or asymptomatic children can infect other people less than adults. Also, the transmission of illness between students at school is less than expected, and the transmission of COVID-19 to students is usually acquired from sick adults rather than sick students. Therefore, with suitable measures, infection risk is less than expected and seems not to be higher than in other public places. COVID-19 measures in schools can be summarized as follows: avoiding crowded/close contact environments as much as possible, respecting the protective (social) distance, wearing appropriate masks, hand hygiene, and some essential protective measurements of classrooms and environment. Measurements should be participatory (students, teachers, education staff, parents, administration), applicable, sustainable, and flexible according to the conditions.

Quadrivalent Influenza Vaccine Prevents Illness and Reduces Healthcare Utilization Across Diverse Geographic Regions During Five Influenza Seasons: A Randomized Clinical Trial.

BACKGROUND: We evaluated an inactivated quadrivalent influenza vaccine (IIV4) in children 6-35 months of age in a phase III, observer-blind trial. METHODS: The aim of this analysis was to estimate vaccine efficacy (VE) in preventing laboratory-confirmed influenza in each of 5 independent seasonal cohorts (2011-2014), as well as vaccine impact on healthcare utilization in 3 study regions (Europe/Mediterranean, Asia-Pacific and Central America). Healthy children were randomized 1:1 to IIV4 or control vaccines. VE was estimated against influenza confirmed by reverse transcription polymerase chain reaction on nasal swabs. Cultured isolates were characterized as antigenically matched/mismatched to vaccine strains. RESULTS: The total vaccinated cohort included 12,018 children (N = 1777, 2526, 1564, 1501 and 4650 in cohorts 1-5, respectively). For reverse transcription polymerase chain reaction confirmed influenza of any severity (all strains combined), VE in cohorts 1-5 was 57.8%, 52.9%, 73.4%, 30.3% and 41.4%, respectively, with the lower limit of the 95% confidence interval >0 for all estimates. The proportion of vaccine match for all strains combined in each cohort was 0.9%, 79.3%, 72.5%, 24.1% and 28.6%, respectively. Antibiotic use associated with influenza illness was reduced with IIV4 by 71% in Europe, 36% in Asia Pacific and 59% in Central America. CONCLUSIONS: IIV4 prevented influenza in children 6-35 months of age in each of 5 separate influenza seasons in diverse geographical regions. A possible interaction between VE, degree of vaccine match and socioeconomic status was observed. The IIV4 attenuated the severity of breakthrough influenza illness and reduced healthcare utilization, particularly antibiotic use.

Clinical Presentation of Influenza in Children 6 to 35 Months of Age: Findings From a Randomized Clinical Trial of Inactivated Quadrivalent Influenza Vaccine.

BACKGROUND: In an exploratory analysis of an inactivated quadrivalent influenza vaccine (IIV4) trial in children 6-35 months without risk factors for influenza, we evaluated clinical presentation of influenza illness and vaccine impact on health outcomes. METHODS: This phase III trial was conducted in 13 geographically diverse countries across 5 influenza seasons (2011-2014). Children were randomized 1:1 to IIV4 or control. Active surveillance was performed for influenza-like episodes (ILE); influenza was confirmed by reverse transcription polymerase chain reaction (RT-PCR). The total vaccinated cohort was evaluated (N = 12,018). RESULTS: 5702 children experienced ≥1 ILE; 356 (IIV4 group) and 693 (control group) children had RT-PCR-confirmed influenza. Prevalence of ILE was similar in RT-PCR-positive and RT-PCR-negative cases regardless of vaccination. Breakthrough influenza illness was attenuated in children vaccinated with IIV4; moderate-to-severe illness was 41% less likely to be reported in the IIV4 group than the control group [crude odds ratio: 0.59 (95% confidence intervals: 0.44-0.77)]. Furthermore, fever >39°C was 46% less frequent following vaccination with IIV4 than with control [crude odds ratio: 0.54 (95% confidence intervals: 0.39-0.75)] in children with breakthrough illness. Health outcome analysis showed that, each year, IIV4 would prevent 54 influenza cases per 1000 children and 19 children would need to be vaccinated to prevent 1 new influenza case. CONCLUSIONS: In addition to preventing influenza in 50% of participants, IIV4 attenuated illness severity and disease burden in children who had a breakthrough influenza episode despite vaccination.

[Results of the use of micafungin in newborns]. / Yenidoganlarda mikafungin kullanimi sonuçlari.

Invasive candidiasis is a common and serious infection in premature newborns. Preventing and treating fungal infections is very important to improve the prognosis of premature infants. Fluconazole and amphotericin B are used as the first choice in the treatment of invasive fungal infections of the newborns. In some cases, fluconazole and amphotericin B cannot be used due to nephrotoxicity, hepatotoxicity or resistant strains. Micafungin, which is among recently developed echinocandins, is the drug of choice in these cases. The use of micafungin in newborns is new and there is a limited experience about the effect of high dose usage in the central nervous system. The aim of this study was to evaluate the electronic files of patients who used micafungin for the treatment of culture-proven or possible invasive fungal infection during their hospital stay in the neonatal intensive care unit during a 24-month period (2016-2017) in the third-level intensive care unit. A total of 15 patients (10 premature and 5 term babies) were included in the study. The mean birth weight of the patients was 1732 ± 999 g and the mean gestational age was 32.2 ± 5.8 weeks. All patients had long-term intensive care and increased risk of invasive candidiasis infection. Central venous catheterization and multiple antibiotics usage were the most common risk factors in these patients. The other risk factors included intubation, total parenteral nutritional use and surgical procedure application. Candida species were isolated from the cultures of four patients. Candida species isolated from patients were Candida albicans, Candida glabrata, Candida catenulata, Candida parapsilosis. The mean time for onset of micafungin was 29.9 ± 16.6 days. Mean duration of micafungin therapy was 22.4 ± 11.2 days. Eight patients received amphotericin B, three patients received fluconazole therapy and four patients did not receive any antifungal therapy before the onset of micafungin. None of these patients had an abnormal kidney or liver function tests due to micafungin use. As a conclusion, high dose (10 mg/kg/day) micafungin is a safe and effective treatment choice both in the treatment of neonatal culture proven or probable invasive candida infections that were caused by refractory Candida strains, and in the case of nephrotoxicity and hepatotoxicity.

The prevalence, serogroup distribution and risk factors of meningococcal carriage in adolescents and young adults in Turkey.

The serogroup epidemiology of invasive meningococcal disease (IMD), which varies considerably by geographic region and immunization schedule, changes continuously. Meningococcal carriage data are crucial for assessing IMD epidemiology and designing f potential vaccination strategies. Meningococcal seroepidemiology in Turkey differs from that in other countries: serogroups W and B are the predominant strains for IMD during childhood, whereas no serogroup C cases were identified over the last 10 y and no adolescent peak for IMD was found. There is a lack of data on meningococcal carriage that represents the whole population. The aims of this multicenter study (12 cities in Turkey) were to evaluate the prevalence of Neisseria meningitidis carriage, the serogroup distribution and the related risk factors (educational status, living in a dormitory or student house, being a household contact with Hajj pilgrims, smoking, completion of military service, attending bars/clubs) in 1518 adolescents and young adults aged 10-24 y. The presence of N. meningitidis DNA was tested, and a serogroup analysis was performed using polymerase chain reaction. The overall meningococcal carriage rate was 6.3% (n = 96) in the study population. A serogroup distribution of the 96 N. meningitidis strains isolated from the nasopharyngeal specimens revealed serogroup A in 5 specimens (5.2%), serogroup B in 9 specimens (9.4%), serogroup W in 64 specimens (66.6%), and serogroup Y in 4 specimens (4.2%); 14 were classified as non-grouped (14.4%). No serogroup C cases were detected. The nasopharyngeal meningococcal carriage rate was 5% in the 10-14 age group, 6.4% in the 15-17 age-group, and 4.7% in the 18-20 age group; the highest carriage rate was found in the 21-24 age group (9.1%), which was significantly higher than those of the other age groups (p < 0.05). The highest carriage rate was found in 17-year-old adolescents (11%). The carriage rate was higher among the participants who had had close contact with Hajj/Umrah pilgrims (p < 0.01) or a history of upper respiratory tract infections over the past 3 months (p < 0.05). The nasopharyngeal carriage rate was 6.3% among adolescents and young adults in Turkey and was similar to the recent rates observed in the same age groups in other countries. The most prevalent serogroup was W, and no serogroup C cases were found. In conclusion, the present study found that meningococcal carriage reaches its peak level by age 17, the highest carriage rate was found in 21 - to 24 - year-olds and the majority of the carriage cases were due to serogroup W. Adolescents and young adult carriers seem to be a potential reservoir for the disease, and further immunization strategies, including adolescent immunization, may play a role in the control of IMD.

Potential Cost-Effectiveness of RSV Vaccination of Infants and Pregnant Women in Turkey: An Illustration Based on Bursa Data.

BACKGROUND: Worldwide, respiratory syncytial virus (RSV) is considered to be the most important viral cause of respiratory morbidity and mortality among infants and young children. Although no active vaccine is available on the market yet, there are several active vaccine development programs in various stages. To assess whether one of these vaccines might be a future asset for national immunization programs, modeling the costs and benefits of various vaccination strategies is needed. OBJECTIVES: To evaluate the potential cost-effectiveness of RSV vaccination of infants and/or pregnant women in Turkey. METHODS: A multi-cohort static Markov model with cycles of one month was used to compare the cost-effectiveness of vaccinated cohorts versus non-vaccinated cohorts. The 2014 Turkish birth cohort was divided by twelve to construct twelve monthly birth cohorts of equal size (111,459 new-borns). Model input was based on clinical data from a multicenter prospective study from Bursa, Turkey, combined with figures from the (inter)national literature and publicly available data from the Turkish Statistical Institute (TÜÏK). Incremental cost-effectiveness ratios (ICERs) were expressed in Turkish Lira (TL) per quality-adjusted life year (QALY) gained. RESULTS: Vaccinating infants at 2 and 4 months of age would prevent 145,802 GP visits, 8,201 hospitalizations and 48 deaths during the first year of life, corresponding to a total gain of 1650 QALYs. The discounted ICER was estimated at 51,969 TL (26,220 US $ in 2013) per QALY gained. Vaccinating both pregnant women and infants would prevent more cases, but was less attractive from a pure economic point of view with a discounted ICER of 61,653 TL (31,106 US $ in 2013) per QALY. Vaccinating only during pregnancy would result in fewer cases prevented than infant vaccination and a less favorable ICER. CONCLUSION: RSV vaccination of infants and/or pregnant women has the potential to be cost-effective in Turkey. Although using relatively conservative assumptions, all evaluated strategies remained slightly below the threshold of 3 times the GDP per capita.