Ates Kara

Comparison of immunogenicity and tolerability of a virosome-adjuvanted and a split influenza vaccine in children.

Objective. To compare the immunogenicity and safety of a virosome-adjuvanted influenza vaccine (Inflexal V; Berna Biotech, Berne, Switzerland) and a split influenza vaccine (Fluarix; GlaxoSmithKline Biologicals, Rixensart, Belgium) in children. Subjects and methods. The subjects, 453 children ages 6 to 71 months, were stratified into primed and unprimed and age groups (6 to 35 and 36 to 71 months) and then randomized 1:1 to receive virosome-adjuvanted (n = 224) or split influenza vaccine (n = 229), a half or full dose was given intramuscularly according to age. Unprimed children received a second dose after 4 weeks. Blood samples (n = 326) collected pre-and 28 days postvaccination were analyzed by hemagglutination inhibition test. Safety assessments were made at baseline and follow-up visits by the investigators and by parents for the 4 days after vaccinations. Results. Both vaccines induced an effective immune response. Seroconversion rates (>4-fold titer rise) against the WHO recommended strains A/New Caledonia (H3N2), A/Moscow (H1N1) and B/Hongkong (B) were 80.1, 66.0 and 90.4% for the virosome-adjuvanted and 75.9, 62.9 and 89.4% for the split influenza vaccine, respectively. Unprimed children’s seroconversion rates for H3N2 were significantly higher (P = 0.02) for the virosome-adjuvanted (88.8%) than for split influenza vaccine (77.5%). Seroprotection rates (titer of > 40) for H3N2, H1N1 and B, respectively, were 87.8, 80.1 and 90.4% after vaccination with the virosome-adjuvanted vaccine and 82.9, 78.2 and 89.4% after the split influenza vaccine. Unprimed children’s seroprotection rate was significantly higher (P = 0.03) for H3N2 after the virosome-adjuvanted (88.8%) than those for the split influenza vaccine (78.3%). Equivalent geometric mean titer fold increases were evident for both vaccines. No serious adverse events were seen. Pain/ tenderness, redness and swelling/induration was found in 25.4, 11.2 and 8.9% for the virosome-adjuvanted vaccine and in 24.0, 9.2 and 6.1% for the split influenza vaccine, respectively. The rates of fever, malaise/irritability and shivering was 6.3, 11.6 and 2.7% for the virosome-adjuvanted vaccine and 8.3, 11.8 and 2.6% for the split influenza vaccine, respectively. Conclusions. The virosome-adjuvanted influenza vaccine showed greater immunogenicity over the split influenza vaccine in unprimed children and showed a trend toward better immunogenicity in the rest of the study population. Both vaccines were well-tolerated.

Role of procalcitonin and CRP in differentiating a stable from a deteriorating clinical course in pediatric febrile neutropenia.

In clinical practice, when neutropenic-fever patients present with no microbiologically and clinically defined infection, the risk of underestimating an occult infection is of major concern, the clinicians have to make a decision on when to modify antibiotic therapy. Hence, a reliable, specific, and sensitive marker, which is regulated independently from the leukocyte count and the underlying disease, is needed for the early diagnosis of infections in cases of neutropenic fever. We have evaluated the diagnostic and follow-up value of procalcitonin (PCT) compared with C-reactive protein (CRP) and erythrocyte sedimentation rate in documenting the infection in neutropenic-fever patients undergoing intensive chemotherapy, as evidenced by the durational change in these parameters in the presence of defined infection. Forty-nine patients, who had 60 febrile episodes, and who were hospitalized in the Hacettepe University Ihsan Doğramacı Childrens Hospital between January 1, 2004 and January 1, 2005 were included in this prospective study. All patients had been diagnosed with neutropenic fever after intensive chemotherapy. In our study, PCT and CRP levels were significantly higher in neutropenic-fever patients (group I and group II separately) than in control patients (P<0.001) throughout the study period; but erythrocyte sedimentation rate levels did not show any significant difference (P>0.05). In sequential analyses of patients without documented infections, the median of PCT concentrations shows a tendency to fall after the 8th hour of onset of fever, whereas in patients with documented infections PCT concentrations fell after the 48th hour. In conclusion, our study suggests that PCT, when measured periodically, is a more useful diagnostic inflammation parameter in pediatric neutropenic-fever patients than CRP, both in estimating the severity of the infection and, the duration and origin of the fever. Hence, PCT might be helpful when deciding on initial therapy modification.

Crimean-Congo hemorrhagic fever in children

Abstract Background Crimean-Congo hemorrhagic fever (CCHF) virus causes a severe disease in humans with a mortality up to 30%. In Turkey there has been an increase in the number of cases during years since 2002. Humans of all ages living in endemic areas,especially those who are working as shepherds and toddlers, have high risk of acquiring CCHF. Objectives The epidemiological, clinical, and laboratory characteristics of the children, who were diagnosed as Crimean-Congo hemorrhagic fever (CCHF) were described. Study design The children infected with CCHF virus between April 2008 and October 2009, and hospitalised in Ankara Dışkapı Childrens and Research Hospital were included. Results Laboratory diagnosis was set by detection of CCHF IgM antibodies and/or genetic detection of CCHF virus. Thirtyone cases included to the study, and all were from the northeastern Anatolia and the southern parts of Black sea region. The mean age was 9.45±4.9 years, the proportion of females was 38.7%. The majority (87%) of the cases had the history of tick bite. There was no fatal case. All the patients had the history of fever. Malaise,tonsillopharyngitis, nausea-vomiting, headache, diarrhea, myalgia and rash were the most common symptoms. The mean AST and ALT levels on the admission were 116 (range 25–389) and 61 (range 8–180)U/L respectively. The mean platelet count on admission was 125,000/mm3, and the lowest was 23,000/mm3. The mean of the lowest white blood cell count was 2353/mm3 and the mean of the highest lactate dehydrogenase was 861IU/L. Conclusions The clinical course of CCHF among children seems to be milder than in adults. Tonsillopharyngitis is a common symptom among children with CCHF.

Secondary hemophagocytic lymphohistiocytosis in Turkish children.

Between January 1998 and January 2005, a total of 18 children 2 weeks–72 months of age were diagnosed as having secondary hemophagocytic lymphohistiocytosis. The frequency of secondary hemophagocytic lymphohistiocytosis among total hospitalized patients during this period was 0.05% (18 of 34,250). Of the 18 patients, 8 (44.5%) had bacterial infections; cytomegalovirus and Epstein-Barr virus infections were present in 5 (28%) and 1 (5.5%), patient, respectively. Leishmaniasis was diagnosed in 2 patients (11%), and herpes simplex virus was diagnosed in 2 patients (11%). Six patients died during treatment, and 1 patient was lost to follow-up. The survival rate was 61%.

Effect of aluminum adjuvants on safety and immunogenicity of Haemophilus influenzae type b-CRM197 conjugate vaccine

Abstract Objective : The present study was carried out to evaluate the safety and immunogenicity of the Haemophilus influenzae type b‐CRM197 (Hib‐CRM197) conjugate vaccine in relation to the change of adjuvant from aluminum hydroxide to aluminum phosphate (AlPO4).

Measurement Accuracy of Fever by Tympanic and Axillary Thermometry

As the basic sciences develop, temperature measurement methods and devices were improved. For hundreds of years both in clinics and home, mercury-in-glass thermometer was the standard of human temperature measurements. In this study, we aimed to compare tympanic infrared thermometers with the conventional temperature option, mercury-in-glass thermometer, which is historical standard in the clinical conditions. Methods: A total of 102 randomly selected pediatric patients who admitted to our hospital were enrolled, and simultaneous temperature measurements were performed via axilla and external auditory canal with 3 different techniques. For external auditory recordings, infrared tympanic First Temp Genius for clinical use and Microlife IR 1DA1 for home usage were used. Classic mercury-in-glass thermometers were used for axillary recording. For each method, 886 measurements were performed. Results: The mean results of the axillary mercury-in-glass thermometers, infrared tympanic First Temp Genius, and Microlife IR 1DA1 were 36.8 ± 0.7, 37.5 ± 0.9, 36.9 ± 0.8, respectively. The Bland-Altman plot of differences suggests that 95% of the infrared tympanic clinical use thermometer readings were within the limits of agreement, which is +0.27 and −1.75°C range of mercury-in-glass thermometer. The Bland-Altman plot of differences suggests that 95% of the tympanic home-use thermometer readings were within the limits of agreement, which is +0.98 and −1.27°C range of mercury-in-glass thermometer. In our group, 15% of the patients were misdiagnosed as febrile with home-use tympanic thermometer, whereas this percentage was 4% with clinical tympanic thermometer. Also, 5% and 31% of febrile patients were misdiagnosed as afebrile with clinical tympanic and home-use tympanic thermometer, if axillary mercury-in-glass thermometer recording defines fever. Discussion: Our results showed that there is a significant difference in each recording with different thermometers, and this variance was present in both higher and lower readings. We recommend thathome-use infrared tympanic thermometer could be used for screening but must not be considered as a tool to decide patients follow-up.

Safety and immunogenicity of a new fully liquid DTPw-HepB-Hib combination vaccine in infants.

We assessed the safety and immunogenicity of a fully liquid, DTPw-HepB-Hib combination vaccine (Quinvaxem™) in comparison with separately administered DTPw-Hib and hepatitis B vaccines. Infants participating in this open-label, randomized, phase II study received a primary vaccination course using a 2-3-4 month schedule. Blood samples were taken immediately prior to the first and one month after the third vaccination. Adverse events were assessed over a 7-day post-vaccination period using subject diaries. After completion of the primary vaccination course, 94.7% [95%CI: 89.8 – 97.7%] of infants receiving the combination vaccine achieved protective anti-HBs antibody titers (?10 mIU/mL) with a mean 39-fold increase in GMTs in comparison with 99.3% [95%CI: 96.3 – 100%] seroprotection and a mean 29-fold GMT increase in the comparator group. Diphtheria, tetanus, and Haemophilus influenzae type B (Hib) seroprotection rates and pertussis seroconversion rates were also similar between the two groups. There was no statistically significant difference in GMTs for diphtheria between the two groups, but significant differences were shown for tetanus, Hib, and pertussis with higher GMTs for each antigen observed in the comparator group. The combination vaccine was well tolerated, with fever (body temperature 38°C) being the most frequently reported adverse event in both the DTPw-HepB-Hib (12.5% [95%CI: 7.7 – 18.8%]) and comparator (12.6% [95%CI: 7.7 – 19.0%]) groups. This study demonstrated that the fully liquid DTPw-HepB-Hib combination vaccine has safety and immunogenicity profiles similar to the DTPw-Hib and hepatitis B vaccines when administered separately.

Influenza Vaccine Adverse Event and Effect on Acceptability in Pediatric Residents

Despite the demonstrated benefits of influenza vaccinations, the coverage is lower than expected among health-care personnel (HCP). In this study we surveyed the attitudes of pediatric residents regarding influenza immunization and adverse reactions. Forty-five female and 35 male pediatric residents with ages ranging from 24 to 28 years were vaccinated with an influenza vaccine on 2 days in the 3rd week of September 2005 by the same nurse. Among our resident, 27 (33.7%) thought the vaccine unnecessary; their vaccine coverage was only 12% in the previous year. Thirteen residents (16%) had soreness at the vaccination site; 7 (8%) had other local reactions that did not interfere with everyday activities, and 16 (20%) had any systemic side effects. The overall rate of side effects from the vaccination was 36.5% (n=29). Twenty of the 29 vaccinees who experienced side effects stated they did not want to receive the vaccine the following year because of the side effects, while 13% in the group without side effects stated the same thing, mainly because of the cost of vaccination. We would like to recommend an influenza vaccination campaign for HCP by employers, but first we must plan to take steps to improve the acceptability of the influenza vaccine among HCP.C vaccine delivery methods for prevention of global childhood diseases carry a high risk for needle contamination, vaccine wastage, and transportation and storage difficulties. Aktiv-Dry LLC’s focus is on R&D of safe and effective microparticles of vaccines and pharmaceuticals for easier storage, greater thermal stability, and ease of use. We utilize our patented CO2-Assisted Nebulization with a Bubble Dryer® (CAN-BD) system to create stable dry microparticles of compounds for administration by needle-free aerosol inhalers, sublingual solid formulations, or safer unit-dose, all-in-one auto-reconstitution syringe devices. Recently, our work has focused on vaccine prevention of measles and hepatitis B. Aktiv-Dry has developed inhalable and sublingual vaccines for measles along with a human-powered, active dry powder inhaler called the PuffHaler® for intrapulmonary delivery of the dry powder measles vaccine. CAN-BD processed measles vaccine shelf-life stability has been shown for 4 years at 2-8oC, protective immunity after intrapulmonary delivery to rhesus macaques, and no serious adverse events reported to date during on-going clinical Phase I safety trials in 60 adult males in India. We have also demonstrated stability of CAN-BD processed and dried microparticles of hepatitis B vaccine for use in a preloaded, single-dose, field-reconstitution device for parenteral delivery. Aktiv-Dry-formulated hepatitis-B vaccine was stabilized with trehalose, processed, and determined to retain stability using in-house stability assays. Our immunogenicity results from intrapulmonary mucosal membrane delivery of measles vaccine dry powder aerosols and fundamental project goals may be extended to prevention and treatment (e.g., antibiotics and antivirals) of other pulmonary diseases (e.g., tuberculosis and influenza). Jessica M.H. Thrall et al., J Vaccines Vaccin 2013, 4:5 http://dx.doi.org/10.4172/2157-7560.S1.017

Mumps meningoencephalitis effect on hearing.

Sensorineural hearing loss is an important complication of mumps. Audiologic tests of 26 children with mumps meningoencephalitis, 25 uncomplicated mumps cases and 20 control cases were performed, and hearing level thresholds at speech and high frequencies were determined. The mean hearing level thresholds in the mumps meningoencephalitis group were higher than those of mumps cases at frequencies from 6,000 to 18,000 Hz in the right ear and at 250 and from 4,000 to 18,000 Hz in the left ear (P < 0.05). Mumps meningoencephalitis cases had higher mean hearing thresholds than did control groups at all frequencies other than 125 and 250 Hz in the right ear and 10,000 Hz in the left ear. The mean hearing thresholds of mumps cases were higher than those of control group at frequencies of 1,000 and 4,000 Hz in the right ear and 1,000 and 10,000 Hz in the left ear (P < 0.05). These results show that mumps meningoencephalitis causes a higher risk of hearing loss than does mumps.

Saccharomyces boulardii CNCM I-745 in different clinical conditions

Introduction: Saccharomyces boulardii is a well-known probiotic worldwide, and there are numerous studies including experimental and clinical trials in children and adults by the use of S. boulardii. Areas covered: The objective of the present report is to provide an update on the evidence for the efficacy of S. boulardii CNCM I-745 in different clinical conditions. Saccharomyces boulardii is one of the best-studied probiotics in acute gastroenteritis (AGE) and is shown to be safe and to reduce the duration of diarrhea and hospitalization by about 1 day. Saccharomyces boulardii is one of the recommended probiotics for AGE in children by European Society of Paediatric Infectious Diseases and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Saccharomyces boulardii is also a recommended probiotic for the prevention of antibiotic-associated diarrhea (AAD), and a recent study showed promising results for the treatment of AAD in children. There is insufficient evidence to recommend the long-term use of S. boulardii in patients with irritable bowel syndrome. Although some clinical studies showed positive effects of S. boulardii on inflammation, there is no clinical evidence that S. boulardii is useful in inflammatory bowel disease. Saccharomyces boulardii could be used in patients needing Helicobacter pylori eradication because the S. boulardii improves compliance, decreases the side effects and moderately increases the eradication rate. There are new promising results (improving feeding tolerance, shorten the course of hyperbilirubinemia), but we do still not recommend the routine use of S. boulardii in newborns. Expert opinion: Saccharomyces boulardii CNCM I-745 is a good example for the statement that each probiotic needs to be taxonomically characterized and its efficacy and safety should be documented individually in different clinical settings.