Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study.

BACKGROUND: Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population. METHODS: This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2-4, 5-10 and 11-17years), was conducted in Poland and the Russian Federation. For the 2-4years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31days post-vaccination, respectively, and serious AEs (SAEs) throughout the study. RESULTS: Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child. CONCLUSION: PHiD-CV was immunogenic and well tolerated in 2-17-year-old children with asplenia or splenic dysfunction. Clinical Trial Registry: www.clinicaltrials.gov, NCT01746108.

Incidence of pertussis in patients of general practitioners in Poland.

We estimated the incidence of pertussis in patients consulting general practitioners (GPs). Between July 2009 and April 2011, we conducted a prospective cohort study of patients attending 78 general practices (158 863 persons overall). We included patients aged ≥ 3 years, with cough lasting 2-15 weeks, who gave informed consent. GPs interviewed eligible patients, collected a blood specimen, and a nasopharyngeal swab. At follow-up 30-60 days after the initial visit, physicians collected a second blood specimen and conducted patient interview. Cases were confirmed by specific IgA and/or IgG antibody titre exceeding significantly the general population background level or detection of bacterial DNA by real-time PCR. During the study period, 3864 patients with prolonged cough consulted the participating GPs, of those 1852 met the inclusion criteria, 1232 were recruited, and 288 were confirmed as pertussis cases (4% by PCR, 96% by serology). The adjusted incidence rate was 201.1/100 000 person-years [95% confidence interval (CI) 133.9-302.0], ranging from 456.5 (95% CI 239.3-870.8) in the 15-19 years group to 94.0 (95% CI 33.4-264.5) in the 25-29 years group. The reporting ratio was 61, ranging from 4 in those aged 3-5 years, to 167 in those aged 65-69 years. The study confirmed high incidence of pertussis in all age groups in the general population, in particular in adults, not appropriately documented by the existing surveillance system.

A phase II, randomised clinical trial to demonstrate the non-inferiority of low-dose MF59-adjuvanted pre-pandemic A/H5N1 influenza vaccine in adult and elderly subjects.

BACKGROUND: Effective planning and preparedness against a possible future A/H5N1 influenza pandemic is a major global challenge. Because dose sparing strategies are required to meet the global demand for vaccine, efforts have focused on the development of adjuvanted vaccine formulations of relatively lower antigen content. AIM: This study aimed to demonstrate the non-inferiority of a low-antigen-dose (3.75 µ) [DOSAGE ERROR CORRECTED] A/H5N1 pre-pandemic vaccine compared with a licensed, higher-dose (7.5 mg) formulation in adult and elderly subjects. Immunogenicity was assessed according to European and U.S. licensure criteria. METHODS: A total of 722 subjects were randomized in equal numbers to receive either the licensed or low-dose formulation. All subjects received two vaccine doses administered three weeks apart. Immunogenicity was assessed three weeks after the administration of each vaccine dose by hemagglutination inhibition (HI), single radial haemolysis (SRH) and microneutralization assays (MN). Local and systemic reactions were assessed over a seven day period post-vaccination. Adverse events were recorded throughout. RESULTS: The low-dose vaccine was demonstrated to be non-inferior to the licensed formulation in terms of antibody titres against the vaccine strain. All three European licensure criteria were met by adult subjects in response to the low-dose vaccine; two criteria were met by the elderly age group. Cross-reactive antibodies were detected against the heterologous A/H5N1 antigen strains A/Indonesia/05/05 and A/turkeyTurkey/01/05. Both vaccines were generally well tolerated by both age groups. CONCLUSION: These data demonstrate that a low antigen dose in combination with MF59 adjuvant is adequate for the routine pre-pandemic immunization of adult and elderly subjects.

A novel combined Hib-MenC-TT glycoconjugate vaccine as a booster dose for toddlers: a phase 3 open randomised controlled trial.

OBJECTIVE: To study the immunogenicity and reactogenicity of a combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) when administered as a booster dose in combination with a measles, mumps and rubella vaccine (MMR). DESIGN: A phase 3 open randomised controlled trial. SETTING: One centre in Oxford, UK and nine centres in Poland. SUBJECTS: 12-15-month-old healthy children. INTERVENTIONS: In the primary stage of the study 500 healthy 6-12-week-old infants were randomised in a 3:1 ratio to receive Hib-MenC-TT+DTPa-IPV or MenC-CRM197 vaccine+DTPa-IPV-Hib. In the booster stage, 476 participants (190 in the UK and 286 in Poland) were vaccinated with Hib-MenC-TT and MMR. MAIN OUTCOME MEASURES: The proportion of children with protective serum antibody levels against MenC and Hib 6 weeks following a Hib-MenC-TT booster dose. RESULTS: The co-primary objectives were met: the Hib-MenC-TT booster dose induced protective antibody titres in children vaccinated with Hib-MenC-TT+DTPa-IPV or MenC-CRM197+DTPa-IPV-Hib at 2, 3 and 4 months of age. 94.8% (lower limit of (LL) 95% CI 92.4) of participants had rSBA-MenC >or=1:128 and 100% (LL 95% CI 99.2) achieved anti-PRP concentrations >or=1.0 microg/ml. The percentage of toddlers with a post boost rSBA-MenC of 1:128 was significantly higher after priming with Hib-MenC-TT (97.7%) than after MenC-CRM197 (86%) (difference: 11.7%; 95% CI 6.2 to 19.4). CONCLUSION: The waning antibody titres against Hib and MenC following primary immunisation can be boosted to protective levels by administering the Hib-MenC-TT vaccine at 12-15 months of age, supporting the recent introduction of this vaccine in the UK immunisation schedule to sustain protection of children against Hib and MenC disease. TRIAL REGISTRATION NUMBER: NCT00258700. Study ID: 103974 (http://clinicaltrials.gov).

[Hepatitis B virus infection in children]. / Wirusowe zapalenie watroby typu B u dzieci.

Retrospective analysis of 256 medical records of children with confirmed diagnosis of hepatitis B virus infection was done. The study focused on significance of patient's age and sex in the course of the disease, on circumstance accompanying the HBV infection and on course of infection, especially a chronic HBV infection. It has been found that factors increasing the risk of infection include: former hospitalizations, surgical procedures, malfunctions of an immune system and familial contacts. Hepatitis occurred more frequently in infants and young children and in this age it more often converted into a chronic form. The course of hepatitis infection depended on dynamics of the disease process. Seroconversion occurred more often after acute phase of the disease and asymptomatic course of infection most often resulted in chronic form. Treatment with immuno-potent (TFX, isoprinosine) had no effect on the course of hepatitis B infection. It should be recommended to extend prophylaxis to children of the risk group and to introduce routine test for HBs antigen in each inpatient child.

[Effect of Zovirax on the course of Varicella-zoster virus (VZV) infections in children with decreased immune response]. / Wplyw Zoviraxu na przebieg zakazen wirusem Varicella-zoster (VZV) u dzieci z oslabiona odpowiedzia immunologiczna.

In 21 children with weakened immune response++ (18 patients after immunosuppression and/or after radiotherapy because of neoplastic disease, 1 patients with diagnosed hepatitis chronica persistens, 1 patient with streptococcal septicemia and one infant with protein deficiency and severe anemia) Zovirax was applied in treatment of Varicella virus infection. Clinical observation showed a positive effect of Zovirax in treatment of VZV infection which was manifested by a milder course of the infection and disappearance symptoms. Better effects were obtained when the treatment was started in the first 72 hours of infection.