Differences In Geometric Mean Concentrations Research Articles

Explore the optimal timing for administering the second dose of the varicella vaccine in China.

The prevalence of varicella in China has been increasing annually, with a relatively high incidence rate of breakthrough cases. Administering two doses of the varicella vaccine (Varv) proves to be the most effective measure. The objective of this study is to assess the immunogenicity of two doses of the Varv at varying intervals and explore the optimal timing for administering the second dose of the Varv. Utilizing a prospective cohort study design, the quantification of varicella immunoglobulin G (IgG) antibodies' geometric mean concentrations (GMC) is conducted through glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). A total of 903 infants were included in the per-protocol population. After completing the first dose of the Varv, the GMC of antibody after 1 month (Group A) was 463.8 (447.6-480.1) mIU/mL. There was a statistically significant difference in GMC and seroconversion rates among the groups (B/C/D) that received the second dose of the Varv (p < 0.05). Multiple comparisons revealed that the group with a 3-year interval between the two vaccine doses had a higher GMC of 665.2 (622.6-707.8) mIU/mL compared to the group with a 1-year interval of 611.1 (577.1-645.3) mIU/mL and the group with a 5-year interval of 564.7 (540.1-589.4) mIU/mL. To effectively prevent and control the varicella epidemic in Jiangsu Province, two dose Varvvaccination is recommended, the optimal time point for the second dose Varvis 3 years after the first vaccination.

Immunogenicity of the UK group B meningococcal vaccine (4CMenB) schedule against groups B and C meningococcal strains (Sched3): outcomes of a multicentre, open-label, randomised controlled trial

The use of the multicomponent meningococcal vaccine 4CMenB in the UK schedule at 2, 4, and 12 months of age has been shown to be 59·1% effective at preventing invasive group B meningococcal disease. Here, we report the first data on the immunogenicity of this reduced-dose schedule to help to interpret this effectiveness estimate. In this multicentre, parallel-group, open-label, randomised clinical trial, infants aged up to 13 weeks due to receive their primary immunisations were recruited via child health database mailouts in Oxfordshire and via general practice surgeries in Gloucestershire and Hertfordshire. Infants were randomly assigned (1:1) with permuted block randomisation to receive a 2 + 1 (2, 4, and 12 months; group 1) or 1 + 1 (3 and 12 months; group 2) schedule of the 13-valent pneumococcal conjugate vaccine (PCV13). All infants also received 4CMenB at 2, 4, and 12 months of age, and had blood samples taken at 5 and 13 months. Participants and clinical trial staff were not masked to treatment allocation. Proportions of participants with human complement serum bactericidal antibody (hSBA) titres of at least 4 were determined for group B meningococcus (MenB) reference strains 5/99 (Neisserial Adhesin A [NadA]), NZ98/254 (porin A), and 44/76-SL (factor H binding protein [fHbp]). Geometric mean titres (GMTs) with 95% CIs were also calculated, and concomitant vaccine responses (group C meningococcus [MenC], Haemophilus influenzae b [Hib], tetanus, diphtheria, and pertussis) were compared between groups. The primary outcome was PCV13 immunogenicity, with 4CMenB immunogenicity and reactogenicity as secondary outcomes. All individuals by randomised group with a laboratory result were included in the analysis. The study is registered on the EudraCT clinical trials database, 2015-000817-32, and ClinicalTrials.gov, NCT02482636, and is complete. Between Sept 22, 2015, and Nov 1, 2017, of 376 infants screened, 213 were enrolled (106 in group 1 and 107 in group 2). 204 samples post-primary immunisation and 180 post-boost were available for analysis. The proportion of participants with hSBA of at least 4 was similar in the two study groups. For strain 5/99, all participants developed hSBA titres above 4 in both groups and at both timepoints. For strain 44/76-SL, these proportions were 95·3% (95% CI 88·5-98·7) or above post-priming (82 of 86 participants in group 1), and 92·4% (84·2-97·2) or above post-boost (73 of 79 participants in group 1). For strain NZ98/254, these proportions were 86·5% (78·0-92·6) or above post-priming (83 of 96 participants in group 2) and 88·6% (79·5-94·7) or above post-boost (70 of 79 participants in group 1). The MenC rabbit complement serum bactericidal antibody (rSBA) titre in group 1 was significantly higher than in group 2 (888·3 vs 540·4; p=0·025). There was no significant difference in geometric mean concentrations between groups 1 and 2 for diphtheria, tetanus, Hib, and pertussis post-boost. A very small number of children did not have a protective response against 44/76-SL and NZ98/254. Local and systemic reactions were similar between the two groups, apart from the 3 month timepoint when one group received an extra dose of PCV13 and recorded more systemic reactions. These data support the recent change to the licensed European schedule for 4CMenB to add an infant 2 + 1 schedule, as used in the routine UK vaccine programme with an effectiveness of 59·1%. When compared with historical data, our data do not suggest that effectiveness would be higher with a 3 + 1 schedule, however a suboptimal boost response for bactericidal antibodies against vaccine antigen fHbp suggests a need for ongoing surveillance for vaccine breakthroughs due to fHbp-matched strains. Changing from a 2 + 1 to a 1 + 1 schedule for PCV13 for the UK is unlikely to affect protection against diphtheria, tetanus, and Hib, however an unexpected reduction in bactericidal antibodies against MenC seen with the new schedule suggests that ongoing surveillance for re-emergent MenC disease is important. Bill & Melinda Gates Foundation and the National Institute for Health Research.

Predictors of the immune response to booster immunisation against tetanus in Czech healthy adults.

An evaluation of the relationship between predictors and immune response was conducted using data obtained from a clinical trial in 200 Czech healthy adults aged 24-65 years receiving a booster dose of a monovalent tetanus vaccine in 2017. The response was determined from ELISA antibody concentrations of paired sera obtained before and 4 weeks after the immunisation. While all subjects with initial antibody levels 2.2 IU/ml. The immune response was not affected by sex, age, tetanus vaccine type, concomitant medication, related adverse events or post-vaccination period since there were no significant differences in geometric mean concentrations or seroconversion rates. The seroconversion rate of 56% in smokers was significantly lower than that of 73% achieved in non-smokers. Although the seroconversion rates did not differ between individuals with normal or higher body weight, the adjusted odds ratio (1.3; 95% Cl 1.08-1.60) revealed a positive correlation between seroconversion rate and body mass index (BMI). Although the vaccine-induced response was influenced by pre-vaccination antibody levels, smoking or BMI, the booster immunisation against tetanus produced a sufficient response regardless the predictors.

Urine Excretion of Caffeine and Select Caffeine Metabolites Is Common in the US Population and Associated with Caffeine Intake1–4

Background: Caffeine is a widely consumed psychoactive stimulant and is of epidemiologic interest. Major sources of caffeine are challenging to standardize, and the use of biomarkers is proposed as an alternative means of assessing intake.Objective: We described urine caffeine and caffeine metabolite concentrations (n = 2466) and excretion rates (n = 2261) in the US population ≥6 y by age, sex, race-ethnicity, and caffeine intake (from foods, beverages, and dietary supplements).Methods: We measured caffeine and 14 of its metabolites in spot urine samples from the cross-sectional NHANES 2009–2010 by use of LC-tandem mass spectrometry.Results: Caffeine and its metabolites were detectable in the urine of most persons, generally at concentrations ≥1 μmol/L. Median concentrations (95% CI) ranged from 0.560 (0.497, 0.620) μmol/L to 58.6 (48.6, 67.2) μmol/L; median excretion rates from 0.423 (0.385, 0.468) nmol/min to 46.0 (40.7, 50.2) nmol/min. Urine concentrations and excretion rates for 9 analytes (caffeine, theophylline, paraxanthine, 1-methylxanthine, 1-methyluric acid, 1,3-dimethyluric acid, 1,7-dimethyluric acid, 1,3,7-trimethyluric acid, and 5-acetylamino-6-amino-3-methyluracil) had moderate correlations with caffeine intake (Spearman ρ = 0.55–0.68, P < 0.0001); the remaining analytes had low correlations (ρ = 0.15–0.33, P < 0.0001). We observed larger differences in geometric mean concentrations and excretion rates between the highest vs. lowest quartiles of caffeine intake for these 9 compounds than the rest. Consistent with dietary caffeine intake, we observed that urine concentrations and excretion rates for most compounds were significantly (P < 0.05) higher in men than women, non-Hispanic whites than Hispanics and non-Hispanic blacks, and highest in persons aged 40–59 y.Conclusion: Excretion of caffeine and its metabolites in urine is common in the US population. According to the observed associations between spot urine concentrations or excretion rates with caffeine intake, several of these compounds show promise as potential biomarkers of caffeine intake.

Importance of Timing of Maternal Combined Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Immunization and Protection of Young Infants

Pertussis booster vaccine (Tdap) recommendations assume that pertussis-specific antibodies in women immunized preconception, during, or after previous pregnancies persist at sufficient levels to protect newborn infants. Pertussis-specific immunoglobulin G (IgG) was measured by IgG-specific enzyme-linked immunosorbent assay (ELISA) in maternal-umbilical cord serum pairs where mothers received Tdap during the prior 2 years. Geometric mean concentrations (GMCs) of pertussis antibodies and cord-maternal GMC ratios were calculated. One hundred five mothers (mean age, 25.3 years [range, 15.3-38.4 years]; mean gestation, 39 weeks [range, 37-43 weeks]) immunized with Tdap vaccine a mean of 13.7 months (range, 2.3-23.9 months) previously were included; 72 (69%) had received Tdap postpartum, 31 at a routine healthcare visit and 2 as contacts of another newborn. There was no difference in GMCs for pertussis-specific IgG in maternal delivery or infant cord sera for women immunized before (n = 86) or during (n = 19) early pregnancy. Placental transport of antibodies was 121%-186% from mothers immunized before and during pregnancy, respectively. Estimated GMC of IgG to pertussis toxin was <5 ELISA units (EU)/mL at infant age 2 months (start of infant immunization series). More infants of mothers immunized during pregnancy had pertussis toxin levels estimated to be higher than the lower limit of quantitation of the assay (4 EU/mL) through age 2 months (52% vs 38%; P = .34). Infants of mothers immunized preconception or in early pregnancy have insufficient pertussis-specific antibodies to protect against infection. Maternal immunization during the third trimester, immunization of other infant contacts, and reimmunization during subsequent pregnancies may be necessary.

Immunogenicity, reactogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV7) concurrently administered with a DTPa-HBV-IPV/Hib combination vaccine in healthy infants

Background To evaluate immunogenicity, reactogenicity, and safety of a hexavalent combination vaccine diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus- Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) when coadministered with a 7-valent pneumococcal conjugate vaccine (PCV7). Methods Infants received either a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus- H. influenzae type b vaccine concomitantly with PCV7 or DTPa-HBV-IPV/Hib alone infants were vaccinated at 2, 3 and 4 months (primary immunization) and 12–15 months of age (booster dose). Local and systemic reactions and adverse events were monitored following each dose and compared between groups. Blood was obtained prior to dose 1, one month after dose 3, immediately prior to and 1 month following the booster dose to measure antibody responses to each of the antigens. Results Two hundred and fifty-three subjects (PCV7, 127; Control, 126) were enrolled. Antibody responses were compared in 226 subjects for the primary immunization and 212 for the booster dose (per-protocol (PP) population). Although there were some differences in geometric mean concentrations (GMCs) to the DTPa-HBV-IPV/Hib antigens after the primary series, GMCs for all antigens after the booster dose were similar in both groups, except for diphtheria which was significantly higher in the PCV7 group (PCV7, 7.41 IU/mL; Control, 5.78 IU/mL). Reactogenicity and safety data were compared in 252 infants receiving primary immunization and 235 children receiving the booster dose. Site reactions were similar in both groups. Fever ≥38.0 °C following each vaccination was reported more frequently in the PCV7 group (28.3–50.0%) than in the Control group (15.6–33.6%) whereas fever >39.0 °C occurred only in a few cases and to the same extent in both groups (PCV7, 0.8–2.7%; Control, 1.6–4.1%). Only one reported serious adverse event was characterized as being related to the study vaccines: control subject was hospitalized with a fever. Conclusion DTPa-HBV-IPV/Hib and PCV7 were highly immunogenic, well-tolerated and safe when coadministered at 2, 3 and 4 months of age with a booster dose at 12–15 months of age. These results support the coadministration of PVC7 with DTPa-HBV-IPV/Hib as part of the routine immunization schedule for infants and children.

Natural and vaccine-induced immunity against Haemophilus influenzae type b in patients with β-thalassemia

Natural and vaccine-induced immunity and immunological memory to Haemophilus influenzae type b (Hib) were evaluated in adolescents and adults with β-thalassemia. At baseline 10/23 (43%) unvaccinated patients had naturally acquired anticapsular antibodies >0.15 μg/ml, the threshold of protection, compared to 9/10 (90%) aged-matched controls. Hib-conjugate vaccine (PRP-T) induced protective immune responses in all subjects and there were no differences in geometric mean concentrations at 1 month (GMC) between patients and controls (69.04 versus 40.5, respectively). Vaccine-induced immunological memory was assessed in 12 subjects with β-thalassemia who had been vaccinated against Hib in the past. All subjects had retained PRP > 1 μg/ml at baseline; PRP-T revaccination induced anamnestic responses which were similar, in terms of post vaccination antibody concentration ( P = 0.54) and avidity ( P = 0.08), with primary responses given by previously unvaccinated patients. A single dose of PRP-T induces adequate and long-lasting immunity and should be given in all unvaccinated adolescents and adults with β-thalassemia.

Immunogenicity and immunological memory induced by a 7-valent pneumococcal CRM197 conjugate vaccine in symptomatic HIV-1 infected children

A 7-valent CRM197 conjugate pneumococcal vaccine (PCV)-induced immune response were evaluated in all Greek symptomatic HIV-1 infected children and 21 age-matched controls. PCV immunogenicity was inferior in HIV patients compared with the controls although differences in geometric mean concentrations (GMC) were not significant ( P > .05). Immune responses were strikingly different after anamnestic immunization, given in all study subjects, 12 months later. HIV-positive children achieved lower GMC for all serotypes compared with the controls ( P = .002) and avidity for all except serotype 6B was inferior compared to baseline. Long-term PCV effectiveness is expected to be reduced among symptomatic HIV-1 infected children.

Atmospheric concentrations and deposition of organochlorine pesticides in the US Mid-Atlantic region

Organochlorine pesticides (OCPs) were measured in the atmosphere over the period January 2000–May 2001 at six locations as part of New Jersey Atmospheric Deposition Network (NJADN). Gas phase, particle phase and precipitation concentrations of 22 OCP species, including chlordanes, DDTs, HCHs, endosulfan I and II, aldrin and diedrin, were measured. OCPs are found predominantly in the gas phase in all seasons, representing over 95% of the total air concentrations. Most of the pesticides measured display highest concentrations at urban sites (Camden and New Brunswick), although in many cases the differences in geometric mean concentrations are not statistically significant. The relationship of gas-phase partial pressure with temperature was examined using the Clausius–Clapeyron equation; significant temperature dependencies were found for all OCPs, except aldrin. Atmospheric depositional fluxes (gas absorption into water+dry particle deposition+wet deposition) to the New York–New Jersey Harbor Estuary of selected OCPs were estimated at NJADN sites. Atmospheric concentrations of dieldrin, aldrin and the HCHs are similar to those measured by the Integrated Atmospheric Deposition Network (IADN) in the Great Lake Region. In contrast, concentrations of DDTs, chlordanes and heptachlor are higher in the Mid-Atlantic compared to the Great Lakes, suggesting that the New York–New Jersey Harbor Estuary receives higher fluxes of these chemicals than the Great Lakes.

Metal concentrations in zebra mussels and sediments from embayments and riverine environments of eastern Lake Erie, southern Lake Ontario, and the Niagara River.

Concentrations of 14 metals were studied in the soft tissues of zebra mussels ( Dreissena polymorpha) and sediments from 16 Great Lakes embayments and riverine environments. Samples were collected in 1993 and 1994 during the early and late autumn period when the body mass of mussels is least affected by reproductive activities. There was a significant difference in geometric mean concentrations of all metals except Cu in mussels sampled from different sites, and there was a significant difference in the geometric mean concentrations of all metals but Cd, Mn, and Zn between years. The higher metal concentrations in mussels from this study were generally similar to those in mussels from contaminated European and U.S. locations, and those with lower concentrations were similar to those from uncontaminated European and U.S. locations. Geometric mean sediment concentrations of all metals differed significantly among sites. Sediment concentrations of metals from some sites were above EPA guidelines for moderately polluted harbor sediments. Sites where zebra mussels had higher concentrations of Al, Cr, and V tended to be the same sites as those where sediment concentrations of these metals were also higher. However, there was not a significant statistical relationship between concentrations of metals in zebra mussels and sediments, except for Mg.