Impact of tetanus-diphtheria-acellular pertussis immunization during pregnancy on subsequent infant immunization seroresponses: follow-up from a large randomized placebo-controlled trial.

BACKGROUND: Pertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization. METHODS: This phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6-14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (270/7-366/7 weeks' gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination. RESULTS: 601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5-77.1%) versus placebo (90.0-99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related. CONCLUSIONS: Pertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant's ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02422264.

Serratia marcescens outbreak in a neonatology unit of a Spanish tertiary hospital: Risk factors and control measures.

BACKGROUND: We describe the investigation undertaken and the measures adopted to control a Serratia marcescens outbreak in the neonatology unit of La Paz University Hospital in Madrid, Spain. METHODS: Weekly rectal and pharyngeal screenings for S marcescens were performed in the neonates starting after detection of the outbreak. Environmental samples and samples from health care workers (HCWs) were obtained for microbiological analysis. An unmatched case-control study was carried out to investigate risk factors for infection/colonization. RESULTS: The outbreak began in June 2016 and ended in March 2017, affecting a total of 59 neonates. Twenty-five (42.37%) neonates sustained an infection, most frequently conjunctivitis and sepsis. Multivariate logistic regression identified the following risk factors: parenteral nutrition (odds ratio [OR], 103.4; 95% confidence interval [CI], 11.9-894.8), history of previous radiography (OR, 15.3; 95% CI, 2.4-95.6), and prematurity (OR, 5.65; 95% CI, 1.5-21.8). Various measures were adopted to control the outbreak, such as strict contact precautions, daily multidisciplinary team meetings, cohorting, allocation of dedicated staff, unit disinfection, and partial closure. Hands of HCWs were the main suspected mechanism of transmission, based on the inconclusive results of the environmental investigation and the high number of HCWs and procedures performed in the unit. CONCLUSIONS: S marcescens spreads easily in neonatology units, mainly in neonatal intensive care units, and is often difficult to control, requiring a multidisciplinary approach. Strict measures, including cohorting and medical attention by exclusive staff, are often needed to get these outbreaks under control.

Immunization of preterm infants with GSK's hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine: A review of safety and immunogenicity.

BACKGROUND: Infants with history of prematurity (<37 weeks gestation) and low birth weight (LBW, <2500 g) are at high risk of infection due to functional immaturity of normal physical and immunological defense mechanisms. Despite current recommendations that infants with history of prematurity/LBW should receive routine immunization according to the same schedule and chronological age as full-term infants, immunization is often delayed. METHODS: Here we summarize 10 clinical studies and 15 years of post-marketing safety surveillance of GSK's hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular-pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib) conjugate vaccine, when administered alone, or co-administered with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with history of prematurity/LBW in clinical trials. RESULTS: At least 92.5% of infants with history of prematurity/LBW as young as 24 weeks gestation in clinical studies were seropositive to all vaccine antigens after 3-dose primary vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine, with robust immune responses to booster vaccination. Seropositivity rates and antibody concentrations to hepatitis B and Hib appeared lower in infants with history of prematurity/LBW than term infants. Between 13-30% of medically stable infants with history of prematurity developed apnea after vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine; usually after dose 1. The occurrence of post-immunization cardiorespiratory events appears to be influenced by the severity of any underlying neonatal condition. Most cardiorespiratory events resolve spontaneously or require minimal intervention. GSK's hexavalent DTPa-HBV-IPV/Hib vaccine was well tolerated in co-administration regimens. CONCLUSION: GSK's hexavalent DTPa-HBV-IPV/Hib vaccine alone or co-administered with other pediatric vaccines has a clinically acceptable safety and immunogenicity profile when used in infants with history of prematurity/LBW for primary and booster vaccination. Additional studies are needed in very premature and very LBW infants. However, currently available data support using GSK's hexavalent DTPa-HBV-IPV/Hib vaccine to immunize infants with history of prematurity/LBW according to chronological age.

Bla-OXA48 gene microorganisms outbreak, in a tertiary Children's Hospital, Over 3 years (2012-2014): Case Report.

RATIONALE: Carbapenem-resistant Enterobacteriaceae are an emerging problem in children. Nosocomial spread remains the principal risk factor for acquisition of these microorganisms. PATIENTS CONCERNS: We describe an outbreak of Klebsiella pneumoniae OXA48 (KOXA48) in a tertiary children's hospital during the years 2012 to 2014, as well as the preventive measures put in place in colonized and infected cases. DIAGNOSES: We studied, "in vitro," the KOXA48 susceptibility to antiseptics and surface disinfectants. Moreover, an epidemiological surveillance of infection or colonization by these microorganisms, with molecular typing of the KOXA48, was performed, and carbapenemase genes were confirmed by polymerase chain reaction (PCR). INTERVENTIONS: The bundles recommended (early detection, cohorting of children and health care workers [HCW], contact precautions, etc.) to control the KOXA48 outbreak were taken from those described in the centers for disease control (CDC) 2012 guide, and adapted according to our experience in controlling other outbreaks. OUTCOMES: All the KOXA48 microorganisms isolated from children belonged to the same strain (ST11) and were susceptible to alcohol solutions but not the surface disinfectant previously employed in our hospital (tensoactive). We reinforced the surface disinfection using a double application (tensoactive + alcohol). The outbreak of KOXA48 begun in 2012 (16 cases in neonatal intensive care unit [NICU] and 1 in pediatric intensive care unit [PICU]) ended before the end of the same year and was not transmitted to new patients in 2013 to 2014, despite readmission of some colonized cases, in intensive care units (ICUs) and other units, of our children hospital. LESSONS: Infected children are the tip of the iceberg (3/17) of KOXA48 prevalence making it necessary to identify the cases colonized by these bacteria. At the beginning of the outbreak, the susceptibility of the epidemic strain to antiseptics and surface disinfectants should be studied. Moreover, the measures taken (cohorts, contact precautions, etc.) must be thorough in both colonized and infected cases, immediately, after microbiological diagnosis.

Circulating Antibody 1 and 2 Years After Vaccination With the 13-Valent Pneumococcal Conjugate Vaccine in Preterm Compared With Term Infants.

BACKGROUND: Premature infants have lower short-term immune responses to vaccination than term infants, but patterns of antibody persistence in preterm infants over longer periods are not well established. This study assessed the persistence of antibody response to the 13-valent pneumococcal conjugate vaccine (PCV13) in formerly preterm versus term infants. METHODS: In total, 100 preterm and 100 term infants received PCV13 with routine vaccines at ages 2, 3, 4 and 12 months. Serotype-specific anticapsular immunoglobulin G (IgG)-binding antibodies and opsonophagocytic activity were determined 1 and 2 years after the last PCV13 dose. RESULTS: At 1 and 2 years after the last vaccination (toddler dose), IgG geometric mean concentrations (GMCs) for all serotypes had declined from levels measured 1 month after the toddler dose but remained above pretoddler dose levels. IgG GMCs were significantly lower in preterm than term subjects for a majority of serotypes at both follow-up time points. IgG GMCs increased in both groups for some serotypes from the 1-year to 2-year follow-up, whereas others declined. Opsonophagocytic activity results supported the IgG results. CONCLUSIONS: The routine (3 + 1) vaccination schedule is likely to offer long-term protection against invasive pneumococcal disease in preterm infants and should be initiated regardless of gestational age or weight at birth, without delay of the toddler dose.

Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.

In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.

13-valent pneumococcal conjugate vaccine (PCV13) in preterm versus term infants.

OBJECTIVES: This study evaluated the immune response and safety profile of 13-valent pneumococcal conjugate vaccine (PCV13) in preterm infants compared with term infants. METHODS: This Phase IV, open-label, 2-arm, multicenter, parallel-group study enrolled 200 healthy infants (preterm, n = 100; term, n = 100) aged 42 to 98 days. All subjects received PCV13 at ages 2, 3, 4 (infant series), and 12 (toddler dose [TD]) months, together with routine vaccines (diphtheria-tetanus-acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine and meningococcal group C conjugate vaccine). RESULTS: Most subjects achieved an anticapsular immunoglobulin G (IgG) antibody concentration ≥ 0.35 µg/mL for all serotypes: >85% after the infant series (except preterm infants for serotypes 5, 6A, and 6B) and >97% after TD (except for serotype 3). Preterm infants had overall lower IgG geometric mean concentrations compared with term infants; however, geometric mean fold increases after TD were similar for all serotypes. Opsonophagocytic activity results were consistent with IgG results and titers increased after TD in both groups for all serotypes, including serotype 3. PCV13 was generally well tolerated, with similar safety profiles in all preterm subgroups. CONCLUSIONS: Immune responses were lower in preterm infants than in term infants. However, the majority of subjects in both groups achieved both pneumococcal serotype-specific IgG antibody levels after the infant series that exceeded the World Health Organization-established threshold of protection and functional antibody responses. Responses were uniformly higher after TD, reinforcing the importance of a timely booster dose. PCV13 was well tolerated regardless of gestational age.

Evaluation of cytomegalovirus infection in low-birth weight children by breast milk using a real-time polymerase chain reaction assay.

Human Cytomegalovirus (CMV) is the most common cause of intrauterine and perinatal infections worldwide. Postnatal CMV transmission has usually no consequences, but in some cases it may produce disease in preterm infants. Literature reports a broad range of breast milk-acquired CMV infections (5.7-58.6%), which depends on the study's design and the treatment of the milk. To evaluate CMV transmission via breast milk, a prospective study using a real-time PCR assay was performed. One hundred and thirty-one mothers (accounting for 160 children) accepted the participation in the study. Urine samples from the infants and breast milk samples from their mothers were collected at 3, 15, 30, 60, and 90 days after delivery. CMV-DNA in breast milk was analysed by quantitative real-time PCR assay Affigene® CMV Trender (Cepheid, Bromma, Sweden). The breast milk samples from 92 mothers (92 of 131, 70.2%) were positive for CMV by PCR. CMV infection was detected in thirteen children by PCR, and four of them (30.7%) had clinical symptoms. There were not significant differences in morbidity between symptomatic and non- symptomatic patients; nonetheless, the average length of hospitalization in symptomatic children was higher than that of non-symptomatic children (P < 0.05). The rtPCR technique is useful for detection of mothers with high viral loads of CMV-DNA in milk, and might be of help to decide whether to freeze the breast milk in preterm children less than 28 weeks.

[Anti-D isoimmunization severe in a twin pregnancy. Case report]. / Isoinmunización grave anti-D en una gestación gemelar. Caso clínico.

Perinatal hemolytic disease occurs secondary to a hemolytic phenomenon of immune origin resulting in fetal or neonatal anemia. A 38-year-old pregnant woman was referred to the Department of high risk Obstetrics, Hospital Universitario La Paz Madrid because of presenting a dichorionic diamniotic twin pregnancy spontaneously, pre-pregnancy diabetes poorly controlled and severe alloinmunization anti-D. Her first pregnancy ended in a normal delivery at term; in the period of 4 years, she has three newborn with 36, 34 and 40 weeks respectively, who die with a week of life. After that, two intrauterine fetal death occur at 26 weeks of gestation. The patient who is RhD negative, suffers anti-D inmunization with a antibody titration of 1/1024 with 14 weeks of gestation. Twelve plasmapheresis, eight doses of anti-D inmunoglobulins and intrauterine transfusions has been the treatment received. A severe anemia is found during the ultrasound control of the middLe cerebral artery peak systolic velocity in both twins since the 16th week. It remains stable thanks to the treatment. Finally at the 28th week of gestation, pregnancy is terminated with a cesarean section. The twins are born alive and premature, but with good general state. The measurement of the middle cerebral artery peak systolic velocity predicts moderate-severe fetal anemia cases, which are the most important in the clinical management because of the need of active treatment or finish the pregnancy.

Five-year antibody persistence and safety following a booster dose of combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine.

BACKGROUND: Booster vaccination with the combined Haemophilus influenza type b-Neisseria meningitides serogroup C-tetanus toxoid vaccine (Hib-MenC-TT) has been reported to induce different MenC antibody responses depending on the priming vaccines, with a possible impact on long-term protection. Here, the five-year persistence of immune responses induced by a booster dose of Hib-MenC-TT was evaluated in toddlers primed with either Hib-MenC-TT or MenC-TT. METHODS: This is the follow-up of a phase III, open, randomized study, in which a Hib-MenC-TT booster dose was given at 13.14 months of age to toddlers primed with either 3 doses of Hib-MenC-TT or 2 doses of MenC-TT in infancy. Children in the control group had received 3 primary doses and a booster dose of MenC-CRM197. Functional antibodies against MenC were measured by a serum bactericidal assay with rabbit complement (rSBA-MenC) and antibodies against Hib polyribosylribitol phosphate by enzyme-linked immunosorbent assay. Serious adverse events considered by the investigator to be possibly related to vaccination were to be reported throughout the study. RESULTS: At 66 months postbooster, rSBA-MenC titers ≥8 were retained by 82.6% of children primed with Hib-MenC-TT, 94.1% of children primed with MenC-TT, and 60.9% of children in the control group. All children who received the Hib-MenC-TT booster dose retained anti- polyribosylribitol phosphate concentrations ≥0.15 µg/mL. No serious adverse events considered possibly related to vaccination were reported. CONCLUSIONS: There is evidence of good antibody persistence against MenC and Hib for more than five years postbooster vaccination with Hib-MenC TT in toddlers primed with Hib-MenC-TT or MenC-TT.

Safety, reactogenicity and immunogenicity of the human rotavirus vaccine in preterm European Infants: a randomized phase IIIb study.

BACKGROUND: Rotavirus disease is more severe in preterm infants than in full-term infants. This study assessed the safety, reactogenicity and immunogenicity of a human rotavirus vaccine, RIX4414, in European preterm infants. METHODS: A total of 1009 preterm infants were randomized (2:1, vaccine:placebo) and stratified into 2 groups: 20% of early (27-30 weeks, group 1) and 80% of late (31-36 weeks, group 2) gestational age preterm infants in each group. Two doses of RIX4414/placebo were administered to these preterm infants according to the recommended chronologic age for full-term infants with an interval of 30-83 days between doses. Serious adverse events were recorded throughout the study period. Solicited and unsolicited adverse events were recorded for 15 and 31 days post-each dose. Antirotavirus IgA concentrations (enzyme-linked immunosorbent assay cutoff = 20 U/mL) and geometric mean concentration were determined pre-dose 1 and 30-83 days post-dose 2 in a subset of 300 infants. This study is registered with ClinicalTrials.gov, number NCT00420745 (eTrack106481). RESULTS: Serious adverse events were reported at a similar frequency in both groups (P = 0.266). Fifty-seven infants reported at least 1 serious adverse event (5.1% [3.5-7.0] in the RIX4414 group and 6.8% [4.3-10.0] in the placebo group). During the 15-day postvaccination follow-up period, diarrhea, vomiting and fever occurred at a similar frequency in both groups; fever could have been due to concomitant vaccines. Five cases (RIX4414 = 3, Placebo = 2) of rotavirus gastroenteritis were reported. The onset of rotavirus gastroenteritis in the RIX4414 group was 1-5 days after vaccination (vaccine strain identified in all cases) and in the placebo group it was 3-4 days after receiving placebo (wild-type rotavirus identified from both cases). Antirotavirus IgA seroconversion rates at 30-83 days post-dose 2 were 85.7% (79.0-90.9) in the RIX4414 group and 16.0% (8.8-25.9) in the placebo group. Geometric mean concentrations were 202.2 U/mL (153.1-267.1) in the RIX4414 group and <20 U/mL in the placebo group. Seroconversion rate in groups 1 and 2 in RIX4414 recipients were 75.9% (95% confidence interval [CI]: 56.5-89.7%) and 88.1% (95% CI: 80.9-93.4%), respectively; the geometric mean concentrations in the respective groups were 110.2 U/mL (95% CI: 56.1-216.5) and 234.8 U/mL (95% CI: 173.4-318.0; exploratory analysis). CONCLUSIONS: Two doses of RIX4414 were immunogenic and well-tolerated in European preterm infants.

Combined Haemophilus Influenzae type B-Neisseria meningitidis serogroup C vaccine is immunogenic and well tolerated in preterm infants when coadministered with other routinely recommended vaccines.

BACKGROUND: Preterm infants are at greater risk of morbidity from vaccine-preventable diseases. Therefore, their responses to vaccination are of particular interest. METHODS: In this open, controlled, Spanish multicenter study, we assessed immunogenicity and safety following primary vaccination of 163 preterm infants (n = 56, <31 weeks' gestation; n = 107, 31-36 weeks' gestation) and 150 full-term infants (>36 weeks' gestation), with Haemophilus Influenzae type B (Hib)-MenC-TT, DTaP(diphtheria-tetanus-acellular pertussis vaccine)-HepB-IPV, and PCV7 at 2 to 4-6 months of age followed by booster vaccination at 16 to 18 months of age. Serum bactericidal activity (rabbit complement) against MenC, and antibodies to Hib and hepatitis b (anti-HBs) were determined. Local/general symptoms were assessed after each vaccination via diary cards. Serious adverse events were recorded throughout the study. RESULTS: There were no statistically significant differences between preterm and full-term infants in either Hib or MenC seroprotection rates or geometric mean concentrations at 1 month postdose 3, before or 1 month postbooster. Postdose 3, >99% of participants had seroprotective anti-HBs antibody concentrations. Anti-HBs geometric mean concentrations was significantly lower in the <31-week group compared with other groups and this difference persisted until 16 to 18 months of age. Hib-MenC-TT vaccine was well tolerated at all ages. There was one death caused by meningococcal serogroup-B sepsis (full term). No serious adverse events were assessed by the investigator as being vaccine related. CONCLUSIONS: Hib-MenC-TT vaccine had a similar immunogenicity and safety profile in preterm and full-term infants. These results demonstrate that preterm infants can be safely vaccinated with Hib-MenC-TT at the recommended chronologic age without impacting the responses to the Hib and MenC antigens.

Immunization of preterm infants with 10-valent pneumococcal conjugate vaccine.

OBJECTIVE: The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in preterm infants were assessed in this study. METHODS: Three parallel groups of infants received 3-dose primary immunization with PHiD-CV at 2, 4, and 6 months of age and a booster dose at 16 to 18 months: preterm I (gestation period ≥ 27 and <31 weeks, N = 50); preterm II (≥31 and <37 weeks, N = 87); and term (≥37 weeks, N = 149). Solicited symptoms and adverse events were recorded. Immune responses to PHiD-CV and coadministered vaccine antigens were measured. RESULTS: The incidence of solicited general symptoms was similar across groups, and the frequency of grade 3 general symptoms was low. Incidences of redness and swelling were generally lower in preterm infants. PHiD-CV was immunogenic for each of the 10 vaccine pneumococcal serotypes (postprimary, ≥92.7% of infants reached enzyme-linked immunosorbent assay antibody concentrations ≥ 0.2 µg/mL and postbooster, ≥97.6%) and for protein D, with a trend for lower postprimary geometric mean antibody concentrations and opsonophagocytic activity (OPA) titers in preterm infants for some pneumococcal serotypes. Postbooster, ≥91.9% of subjects in each group had an OPA titer ≥ 8 for each of the vaccine serotypes. Pneumococcal antibody concentrations and OPA titers after priming and booster vaccination were comparable between the 2 preterm groups. CONCLUSIONS: PHiD-CV was well tolerated and immunogenic in preterm infants when given as a 3-dose primary vaccination, with robust enzyme-linked immunosorbent assay antibody and OPA booster responses in the second year of life.

Immunogenicity and safety of AS03-adjuvanted 2009 influenza A H1N1 vaccine in children 6-35 months.

We report on the evaluation of the immunogenicity and reactogenicity/safety of AS03-adjuvanted vaccine against pandemic influenza A/H1N1/2009 in young children. In this open-label, randomized study, 157 healthy children aged 6-35 months received two doses (21 days apart) of split-virion inactivated A/California/7/2009 H1N1 vaccine containing either (i) 1.9microg hemagglutinin (HA) and AS03(B) (5.93mg tocopherol) (N=104) or (ii) 3.75mug HA and AS03(A) (11.86mg tocopherol) (N=53). At 21 days following the first dose of AS03(B)-adjuvanted vaccine (1.9microg HA) the percentage of children with hemagglutination-inhibition titers of >or=40 against the vaccine strain rose from 3.0% before vaccination to 100%. The seroconversion rate was 99% and the geometric mean titer (GMT) increased from 6 to 313. After the second dose the GMT increased further to 2008. The higher dose AS03(A)-adjuvanted 3.75microg HA vaccine did not further increase the immune response. Solicited symptoms reported within 7 days following vaccination were mainly mild to moderate. After the first dose of AS03(B)-adjuvanted vaccine (1.9microg HA) the most common solicited symptoms were pain at the injection site (35.6%) and irritability (31.7%). Fever (axillary >or=37.5 degrees C) was reported with an incidence of 20.2%. After the second dose reactogenicity tended to increase (injection site pain: 41.3%; irritability: 46.2%; fever >or=37.5 degrees C: 67.3%). Spontaneously reported adverse events with an intensity that prevented normal activities were documented for 2.9-6.7% of doses with only one event (vomiting) considered related to vaccination. There was one serious adverse event reported in the AS03(A)-adjuvanted 3.75microg HA vaccine group (traumatic brain injury) which was not considered as related to vaccination. In conclusion, these data suggest that a first dose of AS03(B)-adjuvanted A/H1N1/2009 vaccine containing 1.9microg HA in children 6-35 months old is highly immunogenic and that the overall reactogenicity profile is acceptable although reactions including fever tend to increase after a second dose.

Hepatitis B response of premature infants after primary and booster immunisation with a diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/haemophilus influenzae type B vaccine.

A range of schedules are recommended for hepatitis B vaccination of premature infants. This open-label study (217744/083) compared the immune response of premature (N = 94) and full-term infants (N = 92) to hepatitis B antigen following primary administration of hexavalent DTPa-HBV-IPV/Hib vaccine at 2-4-6 months and a booster dose at 18 months. Anti-HBsAg antibodies were determined before and one month after primary and booster doses. There were no significant differences in postprimary seroprotection rates (anti-HBsAg >10 mIU/mL; preterm 93.4%; full-term 95.2%) or geometric mean concentrations (634 versus 867 mIU/ml), and neither appeared to be related to gestational length or birth weight. Prebooster seroprotection rates were 75 and 80.6%, respectively. Six premature infants did not respond to primary and booster doses. Primary and booster vaccinations with DTPa-HBV-IPV/Hib elicit satisfactory anti-HBsAg responses in preterm infants, which are not influenced by gestational age or birth weight. This schedule and vaccine will greatly facilitate the immunisation of premature infants.

Laurin-Sandrow syndrome: review and redefinition.

We report on a newborn infant with characteristics of Laurin-Sandrow syndrome (LSS). She had hypertelorism, flat nose with grooved collumella, "V" shaped mouth with thin lips, 7 well-recognized and fused digits and 1 additional postaxial bilateral appendix on each hand. The right and left feet had 12 and 11 toes, respectively, the 4 external ones were recognizable, and the rest were fused in a uniform mass but with independent nails. There was also a 2.3 cm-long digitiform appendix in the internal part of both feet. Radiographs showed seven metacarpals and seven metatarsals with similar morphology; both hands lacking thumbs. The four lateral-most toes had regular shaped phalanges and the rest were irregular. The left digitiform appendix had three bones and the right only two. Tibiae were shorter than fibulae. Central Nervous System examination showed an abnormally shaped olivary nucleus, cerebellar cortical heterotopias, gray matter ectopias in both spinal cord and hemispheric white matter, marked ventricular dilatation, and moderate diffuse white matter gliosis. Karyotype was 46XX. A complete necropsy study is presented and all reported cases are reviewed focusing on their phenotypic differences and their nosologic classification. We propose the entity LSS only in cases with symmetric tetrameric polysyndactyly, especially cup-shaped hands and mirror feet, in association with nasal anomalies.

Immunogenicity and reactogenicity of a booster dose of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine given to toddlers of 13-14 months of age with antibody persistence up to 31 months of age.

BACKGROUND: A combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) may be a convenient alternative to separate Hib and MenC conjugate vaccines. METHODS: Healthy infants randomized in a previous study for priming at 2, 4, and 6 months: Hib-MenC-TT primed group, 3 doses of Hib-MenC-TT + DTPa-HBV-IPV (N = 87); MenC-TT primed group, 2 doses of MenC-TT (NeisVac-C; Baxter Healthcare SA, Zuürich, Switzerland) + 3 doses of DTPa/Hib containing vaccines (N = 178); MenC-CRM primed group, 3 doses of MenC-CRM197(Meningitec; Wyeth Corporation Delaware, Madison, NJ) + DTPa-HBV-IPV/Hib (N = 93). At 13-14 months of age, Hib-MenC-TT and MenC-TT primed groups received a Hib-MenC-TT booster dose and the MenC-CRM primed group a booster dose of DTPa-HBV-IPV/Hib. Blood samples were taken before and at 1 and 18 months postbooster. RESULTS: Before the booster dose, persistence of anti-polyribosyl ribitol phosphate (PRP) antibody concentration > or =0.15 microg/mL in the Hib-MenC-TT (96.4%) and MenC-TT (96.1%) primed groups and of MenC bactericidal titers > or =1:8 in the Hib-MenC-TT primed group (96.3%) was statistically significantly higher than in the MenC-CRM primed group (86.4% and 85.4%, respectively). One month after the Hib-MenC-TT booster, 99.2% subjects in the Hib-MenC-TT primed + MenC-TT primed pooled groups had anti-PRP levels > or =1 microg/mL, and 99.6% had SBA-MenC titers > or =1:128. The Hib-MenC-TT booster tended to be less reactogenic than the DTPa-HBV-IPV/Hib control and no serious adverse events related to vaccination were reported. Eighteen months after boosting with Hib-MenC-TT, SBA-MenC titers > or =1:8 persisted in 92.7% subjects and anti-PRP > or =0.15 microg/mL persisted in 99.4%. CONCLUSIONS: Primary immunization with 3 doses of Hib-MenC-TT coadministered with DTPa-HBV-IPV induced antibodies that persisted up to the second year of life. The Hib-MenC-TT booster administered to primed toddlers induced robust and persistent antibody responses to both the Hib and MenC components and had an acceptable safety profile.