Kanra G

Beneficial effects of dexamethasone in children with pneumococcal meningitis.

Fifty-six children older than 2 years with meningitis caused by Streptococcus pneumoniae were enrolled in a prospective, double blind, placebo-controlled trial to evaluate the efficacy of dexamethasone therapy in addition to antimicrobial therapy. Twenty-nine of 56 received dexamethasone (0.6 mg/kg/day iv, divided into 4 daily doses for 4 days) and the remaining 27 received placebo. At the beginning of therapy the clinical and laboratory characteristics of the patients in the treatment groups were comparable, except for the Glasgow coma score (P = 0.004), which was lower in the dexamethasone group. Patients were examined daily during hospitalization and 6 weeks after discharge from the hospital. Hearing was assessed 6 weeks after discharge by means of pure tone audiometry. Two patients in the dexamethasone group and one patient in the placebo group died. There were no differences between the two groups with regard to the duration of fever, the incidence of secondary fever and electrolyte imbalance, seizure activities occurring during hospitalization and rash. Although the differences were statistically insignificant, moderate or severe unilateral or bilateral sensorineural hearing loss at 6 weeks and the overall neurologic sequelae, including hearing loss, at 1 year were higher in the placebo group, at 23% vs. 7.4% (P = 0.11) and 26.9% vs. 7.4% (P = 0.062), respectively. At 3 months after discharge, because of the improvement in hearing loss in one dexamethasone-treated patient the incidence of hearing impairment was significantly less than that in the placebo group, at 3.7% vs. 23%, respectively (P = 0.044). No improvement in hearing loss was observed after 3 months.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Priming effect, immunogenicity and safety of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular pertussis (DTaP) combination vaccine administered to infants in Belgium and Turkey.

To evaluate the priming effect, immunogenicity and safety of an Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular (two component) pertussis (DTaP) combination vaccine, a randomized, comparative study was conducted in two centers, one in Belgium and one in Turkey. A total of 410 healthy infants, 160 in Belgium and 250 in Turkey, randomly received DTaP and PRP-T vaccines in one of three fashions. One group (N = 138) received DTaP and PRP-T vaccines reconstituted immediately prior to injection at 3, 4 and 5 months of age, and are referred to as the combined, short schedule group (Co-S). A second group (N = 135) received DTaP + PRP-T simultaneously but injected at different sites according to the same schedule, and are referred to as the associated, short schedule group (As-S). The third group (N = 137) also received DTaP + PRP-T at separate sites, but at 2, 4 and 6 months, and are referred to as the associated, long schedule group (As-L). The As-L group allowed for serological bridging with a Senegalese two-component pertussis vaccine efficacy trial, using the same batch of DTaP vaccine. Children of both short-schedule groups (Co-S and As-S) received, at the age of 12-14 months, a booster dose of DTaP vaccine associated with unconjugated PRP vaccine. Mixing of the vaccines did not affect the immune response to the antigens included in the DTaP vaccine. The immune response to Hib capsular polysaccharide, however, was significantly lower after combined administration (Co-S group) than after associated (As-S group) administration (P < 0.0001), with a similar trend among both countries (GMTs, 1.78 microg/ml and 6.19 microg/ml in Belgium, and 5.02 microg/ml and 11.67 microg/ml in Turkey). Booster vaccination with the unconjugated PRP induced a vigorous and similar anamnestic response in both groups. Belgian infants showed a significantly lower immune response to all antigens than Turkish infants (P < or = 0.001 for all antigens), with a similar trend among each study group. In all groups, the incidence of adverse events was lower than that usually reported after DTwP(whole-cell) vaccine. Higher rates of systemic reactions were observed in the Belgian population, possibly due to differences in reporting practice. Our results indicate (1) that the combination vaccine, DTaP//PRP-T, represents an important improvement over the existing uncombined vaccines; (2) that immunogenicity studies should include at least one booster injection to evaluate priming effects by combined vaccines; and (3) that it is feasible and valuable to co-randomize combination vaccine studies in sufficiently different geographical areas and child populations.

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).

Immunogenicity and efficacy of one dose measles-mumps-rubella (MMR) vaccine at twelve months of age as compared to monovalent measles vaccination at nine months followed by MMR revaccination at fifteen months of age

BACKGROUND AND METHODS measles is a common cause of morbidity and mortality in developing countries. Although the measles-mumps-rubella vaccine (MMR) is currently in use in developed countries, monovalent measles vaccine (MV) is routinely recommended by World Health Organization (WHO) at 9 months of age in Turkey, as in many other developing countries. In this study, 442 Turkish children received MV at 9 months of age and were revaccinated with MMR vaccine at 15 months of age. In the second group 495 children received MMR at 12 months of age with no earlier measles vaccination. Antibodies were measured before the first vaccination and 6 weeks after the MMR. All children had been followed for occurrence of measles infection for 60 months. Two vaccination schedules were compared for immunogenicity and protection rates. CONCLUSIONS seroconversion and clinical protection rates were significantly higher in children who received only MMR at 12 months of age than in children revaccinated at 15 months of age. Seroconversion rate for measles was 69.9% in children who received MMR at 12 months of age and 90.3% in children revaccinated at 15 months of age (P=0.0003). While there was no measles case in children who were revaccinated, 12 (2.7%) children in the first group acquired measles during the follow-up period. Vaccination at 12 months of age appeared to be better than the current national standard. The late elimination of maternal antibodies and the inhibitory effect of a weak antibody response after the first dose of vaccine at 9 months may explain the better immunogenicity and efficacy of the MMR vaccine given at 12 months of age.

Immunogenicity study of a combined diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis vaccine used to reconstitute a freeze-dried Haemophilus influenzae type b vaccine (DTaP-IPV//PRP-T) administered simultaneously with a hepatitis B vaccine at two, three and four months of life

This study was designed to assess the immunogenicity of a vaccine combining diphtheria and tetanus toxoids, acellular pertussis vaccine, and inactivated poliovirus vaccine reconstituting Haemophilus influenzae type b polysaccharide conjugated to tetanus protein (DTaP-IPV//PRP-T; Pasteur Mérieux Connaught, Lyon, France) administered simultaneously in association with hepatitis B vaccine (RECOMBIVAX (¿trade mark omitted¿) Merck, Sharp & Dohme, West Point, PA, USA) for the primary immunization of infants. The vaccines were administered at two, three and four months of age. One hundred and sixty-two healthy infants, aged 8-10 weeks, were enrolled in the study. Blood samples were taken before the first dose and 4 weeks after the third dose. The infants were observed for 15 minutes after vaccination for any immediate reaction. Adverse events requiring a medical consultation were recorded by the parents in a diary over the 7 days following vaccination. Four weeks after the third immunization, the percentages of infants fulfilling seroconversion criteria were 98.9% for pertussis toxin, 95.9% for filamentous haemagglutinin, 100.0% for tetanus, 100.0% for diphtheria, 99.3% for poliovirus type 1, 100.0% for both poliovirus types 2 and 3, 98.0% for Haemophilus influenzae type b, and 100% for hepatitis B surface antigen. No vaccine-related serious adverse event was reported. The simultaneous administration of DTaP-IPV//PRP-T and hepatitis B vaccines at two, three and four months of age yielded clinically satisfactory immune responses to all antigens compared with historical controls and gave a good safety profile.

Acellular pertussis diphtheria-tetanus-pertussis vaccine containing separately purified pertussis toxoid, filamentous haemagglutinin and 69 kDa outer membrane protein as a booster in children

In two double-blind, randomized, comparative studies involving a total of 218 children, an acellular pertussis (DTPa) vaccine containing diphtheria and tetanus toxoids and pertussis components filamentous haemagglutinin (FHA), pertussis toxoid (PT), and 69 kDa outer membrane protein (69 kDa OMP) was administered as a booster to 17-month-old and 5-year-old children with a history of routine whole-cell diphtheria-tetanus-pertussis (DTPw) vaccination. The control groups in these studies received DTPw vaccine. Among 17-month-old toddlers, significantly lower proportions of DTPa vaccine recipients had local pain (7.3%), redness (14.5%) and swelling (9.1%) than DTPw vaccine recipients (23.6%, 30.9% and 23.6%, respectively). A trend toward fewer local reactions was also seen in 5-year-old children vaccinated with DTPa in private practice and public clinics although differences were not statistically significant. Fever (rectal temperature ≥38°C) was reported more frequently for DTPw vaccine recipients in both age groups. White no differences existed between groups in terms of geometric mean antibody titres (GMTs) prior to booster vaccination, anti-PT antibody GMTs were higher among DTPa vaccine recipients than among DTPw vaccine recipients after booster vaccination. The difference was statistically significant in 5-year-old subjects. Furthermore, significantly higher anti-FHA and anti-69 kDa OMP GMTs were seen in DTPa vaccine recipients in both age groups. In pre-vaccination seropositive subjects and in pre-vaccination seronegative subjects the rate of immune response to pertussis antigens was higher for DTPa than for DTPw vaccine recipients with the exception of the rate of response induced to 69 kDa OMP in 5-year-old children. The lower frequency of side-effects and similar or greater immunogenicity of DTPa vaccine when used as a booster in subjects primed with DTPw encourage the introduction of this type of vaccine for the fourth and fifth DTP doses that are routinely administered in many countries.

Complement component deficiencies and infection: C5, C8 and C3 deficiencies in three families

Three families are described with complement component deficiencies. In one family, five children had C5 deficiency; in a second family, two children had C8 deficiency and one child in a third family had C3 deficiency. The index cases were identified during screening of patients with recurrent pyogenic infections, recurrent meningitis and meningococcaemia. Two of the five C5 deficient patients had recurrent meningitis and meningococcaemia, two had recurrent respiratory tract infections and otitis and one was healthy. One of the C8 deficient patients had meningitis, meningococcaemia and pneumonia, whereas his sibling with the same deficiency was healthy. The patient with C3 deficiency had four episodes of meningitis and recurrent otitis.

Varicella seroprevalence in a random sample of the Turkish population.

Chicken pox highly contagious and common throughout the world, is an infectious disease caused by varicella zoster virus (VZV). This study was conducted to determine the seroprevalence of VZV in a population under age 30 and to identify the relationship of VZV seroprevalence and several characteristics of the study subjects in nine provinces of Turkey. The sampling method of 30 clusters recommended for field studies was used for selecting subjects of a pre-determined number in the rural and urban areas in each province. For this, a total of 60 groups, 30 clusters in the rural and 30 in the urban areas were determined. It was planned that a total of 4800 subjects, including 600 subjects from five big provinces (Istanbul, Ankara, Izmir, Adana, Diyarbakir) and 450 subjects from the remaining smaller provinces (Samsun, Erzurum, Trabzon, Edirne), be included in the study. ELISA method was used to examine the blood samples for VZV seropositivity. Positive VZV seroprevalence was detected in 77.8% of 4387 subjects under age 30 in nine provinces of Turkey. There was no difference in seroprevalence rate between rural and urban areas. Seroprevalence was found to be 79.0% in urban areas and 76.3% in rural areas. Seroprevalence increased with age. Seroprevalence was 20% at the age of 1 year, subsequently increased to 40% at the age of 4 years, 60% at the age 6 years, 80% at the age of 8 years, 85% at the age of 10 years, and then remained at 85-90% in subjects over the age of 10 years. In order to develop vaccination protocols and take appropriate preventive health care measures against diseases in different countries, it is very important to know the seroprevalence of any disease for an individual country.

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.