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Thailand incorporated the hepatitis B (HepB) vaccine into the infant combination vaccine known as pentavalent wP-containing vaccines (DTwP-HB-Hib) and hexavalent aP-containing vaccines (DTaP-IPV-HB-Hib). We followed healthy children from the clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent or hexavalent vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (at 18 months), following the monovalent HepB vaccine at birth. Blood samples were collected to evaluate the persistence of hepatitis B surface antibody (anti-HBs) at 3, 4, 5, 6 and 7 years of age. The results showed that at 7 years of age, a higher percentage of children in the hexavalent group maintained anti-HBs levels ≥ 10 mIU/mL compared to those in the pentavalent group (86.9 % vs. 59.7 %). This study showed good persistence of anti-HBs among hexavalent-vaccinated children 5.5 years after the last dose of the HepB vaccine.

ABSTRACTIntroduction Hexaxim® is fully liquid, hexavalent, combination vaccine that provides immunization against diphtheria, tetanus, pertussis (whooping cough), polio, hepatitis B, and invasive diseases caused by Haemophilus influenzae type b. Combination vaccines such as Hexaxim reduce the number of injections needed, improving both vaccination compliance and operational efficiency.Areas covered Safety and immunogenicity data were reviewed from >25 clinical trials involving approximately 7200 infants/toddlers, identified using PubMed searches to April 2023. These trials have evaluated a diverse range of primary series and booster schedules, including antibody persistence, co-administration of Hexaxim with other routine pediatric vaccines, and specific populations (born to Tdap-vaccinated women, preterm, and immunocompromised infants). Lastly, post-marketing surveillance and real-world effectiveness data were assessed.Expert opinion An extensive program of clinical development prior to licensure demonstrated favorable vaccine safety and good immunogenicity of each antigen, and Hexaxim was first approved for use in 2012. In the 10 years since licensure, Hexaxim has been adopted widely, with more than 180 million doses distributed worldwide. The widespread use of this hexavalent vaccine is a crucial tool in the ongoing and future control of six pediatric infectious diseases globally.

Cement kiln co-processing is a major technique for disposing of hazardous solid wastes, yet the formation of toxic soluble compounds during the process may induce further contamination upon leaching. Hexavalent chromium compounds are generally considered to be the only soluble chromium species in cement. Here, we identified Ca5(CrO4)3O0.5, a compound with solubility of 10–150 mg/L at 20–50 °C containing pentavalent chromium, in cement co-processed with tanning sludge at temperatures higher than 800 °C. This hexagonal crystal is partly responsible for the leachability of chromium from cement. Approximately 10% of the soluble chromium compounds in the co-processed cement were attributed to the formation of Ca5(CrO4)3O0.5. The formation of Ca5(CrO4)3O0.5 results rather from the reduction of CaCrO4 by free CaO at 800–1300 °C than from the oxidation of trivalent chromium. Our findings imply that the formation of pentavalent chromium during cement production could pose a threat to environmental safety. [ABSTRACT FROM AUTHOR]

The pentavalent DTwP-HB-Hib (Shan-5) vaccine was first introduced into the Thailand Expanded Program on Immunization (EPI) in 2019. The Shan-5 vaccine is administered to infants at 2, 4, and 6 months of age, after initial vaccination with monovalent hepatitis B (HepB) and Bacillus Calmette-Guérin (BCG) vaccines at birth. This study compared the immunogenicity of the HepB, diphtheria, tetanus, and Bordetella pertussis antigens incorporated in the EPI Shan-5 vaccine versus the optional pentavalent (DTwP-HB-Hib) Quinvaxem and hexavalent (DTaP-HB-Hib-IPV) Infanrix-hexa vaccine. Three-dose Shan-5-vaccinated children were prospectively enrolled at the Regional Health Promotion Centre 5, Ratchaburi province, Thailand, between May 2020 and May 2021. Blood sampling was performed at months 7 and 18. The levels of HepB surface antibody (anti-HBs), anti-diphtheria toxoid (DT) IgG, anti-tetanus toxoid (TT) IgG, and anti-pertussis toxin (PT) IgG were evaluated using commercially available enzyme-linked immunoassays. Anti-HBs levels of ≥10 mIU/mL were achieved in 100 %, 99.2 %, and 99.2 % of infants in the Shan-5 EPI group, hexavalent group and Quinvaxem group one month after four dose immunization (at 0, 2, 4, 6 months of age), respectively. The geometric mean concentrations of the EPI Shan-5 and hexavalent groups were comparable but were higher than those of the Quinvaxem group. At one month after primary vaccination (month 7), infants in the Shan-5 EPI group had significantly higher levels of anti-DT IgG, anti-TT IgG, and anti-PT IgG than infants in the hexavalent and Quinvaxem groups. The immunogenicity of the HepB surface antigen in the EPI Shan-5 vaccine was similar to that achieved by the hexavalent vaccine, but was higher than that achieved by the Quinvaxem vaccine. The Shan-5 vaccine is highly immunogenic and generates robust antibody responses after primary immunization. [ABSTRACT FROM AUTHOR]

In South Korea, the ready-to-use hexavalent vaccine (against diphtheria, tetanus, pertussis, poliovirus, Haemophilus influenzae type b, and hepatitis B) is not listed despite its facility of no need to reconstitute. It, therefore, has the potential to augment the efficiency of prevention against the six infectious diseases, and it may reduce vaccine-related errors of reconstitution when compared with the currently used vaccination scheme of the pentavalent vaccine with the additional shots against hepatitis B. Given the assumed clinical equivalence between the two vaccination schemes, a cost-minimization analysis has been performed from a societal perspective including all the medical and non-medical direct and indirect costs when vaccinating one birth cohort. The results indicate that the ready-to-use hexavalent vaccine induces a cost reduction of KRW 47,155 (USD36.22) per infant or 12,026 million Korean Won ($9,236,417) in total for the whole birth cohort with 260,500 children. Using the ready-to-use hexavalent vaccine causes a lower infection rate, has fewer vaccination sessions, and may save much time as compared with the current vaccination scheme in place. The ready-to-use hexavalent vaccine may, therefore, benefit the National Immunization Program by reducing the total societal costs of vaccination while improving convenience of infants, parents, and medical care professionals. [ABSTRACT FROM AUTHOR]

Hexavalent chromium is resistant to degradation and harmful toxic substance to environment and community health. Physicochemical treatment methods are demanding high cost, used large quantities of chemicals & energy, release large amount of secondary toxic degradants. Mycoremediation is an eco-friendly alternative treatment method. The main objective of this research is to isolate and characterize chrome (VI) tolerant fungi from farm soil & industry effluent for mycoremedation purpose. The screening and isolation of yeast was carried out on potato dextrose agar media. PDA and broth assay test for fungi tolerance to hexavalent chromium at different concentration, temperature and pH was evaluated. Fungi species was identified biochemically using Biolog Microstation depending on carbon utilization and chemical sensitivity test. The result revealed that 10 yeast species was identified with full ID from effluent waste and farm soil based on their probability ≥ 75% and similarity index ≥ 0.5 as well as their Cr (VI) tolerance ability up to 2500 ppm. These are Yarrowia lipolytica (100%, 0.7), Cryptococcus luteolus(100%, 0.64), Rhodotorula aurantiaca A(100%, 0.62), Ustilago maydis(100%, 0.58) Trichosporon beigelii B (100%, 0.51), Cryptococcus terreus A (100%, 0.62), Zygosaccharomyces bailii (98%, 0.65), Nadsoniafulvenscens (90%, 0.62), Schizoblastosporonstarkeyihenricii (89%, 0.56), Endomycopsis vivi (84%, 0.62), Rhodotorula pustula (Sim, 0.59). Two yeast species Yarrowia lipolytica and Nadsoniafulvenscens show the highest growth mean Optical density (OD) measure 0.74 ± 0.2 & 0.60 ± 0.2 respectively at pH 7 & 25 °C. The highest tolerance index (mm) was recorded by Schizoblastosporon starkey henricii 0.3067 ± 0.152. Cr (VI)-tolerance ability of these yeast strains used in the development of chromium-bioremediation technologies provide an alternative option for chromium sequestration after HPLC analysis& molecular characterization. [ABSTRACT FROM AUTHOR]

Vaccination during pregnancy with tetanus, diphtheria, acellular pertussis (aP) (Tdap) antigens is important for early protection of newborn infants against pertussis, particularly for preterm infants. This study evaluated the effect of Tdap vaccination during pregnancy on the immunogenicity of a diphtheria (D), tetanus (T), aP, inactivated poliovirus (IPV), hepatitis B (HB), and Haemophilus influenzae type b (PRP ∼ T) vaccine in term and preterm populations. A prospective, observational study (NCT02511327) recruited women and their infants based on delivery (term or preterm) and vaccination status (vaccinated with a Tdap vaccine [Boostrix™, GlaxoSmithKline] during pregnancy or not vaccinated in the last 5 years). All infants received licensed DTaP-IPV-HB-PRP ∼ T (Hexyon™, Sanofi) (8, 12, 16 week primary series and booster at 13 months of age [preterm infants] or 15 months of age [term infants]). Immunogenicity was evaluated using validated assays. Data were pooled into term (N = 127) and preterm infants (N = 105), and infants of women who received a Tdap vaccine during pregnancy (N = 199) or not (N = 33). Before primary vaccination, antibody levels were higher for term than preterm infants for anti-D, anti-polio 1, 2, 3, anti-PT, anti-FHA, and anti-PRP, and similar for anti-HBs and anti-T. At this time, infants of Tdap-vaccinated women had higher anti-D, anti-T, anti-PT, anti-FHA, and anti-PRP antibody levels than infants of Tdap-unvaccinated women; anti-HBs and anti-polio antibody levels were similar in both groups. Post-primary, pre-booster, and post-booster, there were only small differences in seroprotection rates (anti-D, anti-T, anti-polio 1, 2, 3, anti-HBs, anti-PRP) and seroconversion rates (anti-PT, anti-FHA), except for anti-HBs ≥ 10 mIU/mL and anti-PRP ≥ 0.15 µg/mL post-primary vaccination (higher for term [98.31 % and 90.91 %, respectively] versus preterm infants [89.80 % and 79.41 %, respectively]). These data support the use of DTaP-IPV-HB-PRP ∼ T vaccine for primary and booster vaccination in term and preterm born infants and in infants born to Tdap-vaccinated or Tdap-unvaccinated women. [ABSTRACT FROM AUTHOR]

Hexaxim® is fully liquid, hexavalent, combination vaccine that provides immunization against diphtheria, tetanus, pertussis (whooping cough), polio, hepatitis B, and invasive diseases caused by Haemophilus influenzae type b. Combination vaccines such as Hexaxim reduce the number of injections needed, improving both vaccination compliance and operational efficiency. Safety and immunogenicity data were reviewed from >25 clinical trials involving approximately 7200 infants/toddlers, identified using PubMed searches to April 2023. These trials have evaluated a diverse range of primary series and booster schedules, including antibody persistence, co-administration of Hexaxim with other routine pediatric vaccines, and specific populations (born to Tdap-vaccinated women, preterm, and immunocompromised infants). Lastly, post-marketing surveillance and real-world effectiveness data were assessed. An extensive program of clinical development prior to licensure demonstrated favorable vaccine safety and good immunogenicity of each antigen, and Hexaxim was first approved for use in 2012. In the 10 years since licensure, Hexaxim has been adopted widely, with more than 180 million doses distributed worldwide. The widespread use of this hexavalent vaccine is a crucial tool in the ongoing and future control of six pediatric infectious diseases globally. [ABSTRACT FROM AUTHOR]

Hexavalent chromium (Cr(VI)) is a highly mobile cancerogenic and teratogenic heavy metal ion. Among the varied technologies applied today to address chromium water pollution, photocatalysis offers a rapid reduction of Cr(VI) to the less toxic Cr(III). In contrast to classic photocatalysts, Metal-Organic frameworks (MOFs) are porous semiconductors that can couple the Cr(VI) to Cr(III) photoreduction to the chromium species immobilization. In this minireview, we wish to discuss and analyze the state-of-the-art of MOFs for Cr(VI) detoxification and contextualizing it to the most recent advances and strategies of MOFs for photocatalysis purposes. The minireview has been structured in three sections: (i) a detailed discussion of the specific experimental techniques employed to characterize MOF photocatalysts, (ii) a description and identification of the key characteristics of MOFs for Cr(VI) photoreduction, and (iii) an outlook and perspective section in order to identify future trends. [ABSTRACT FROM AUTHOR]

Background: Combination vaccines reduce the number of pediatric injections but must be as safe, immunogenic, and effective as each of the individual vaccines given separately. Additionally, consistency in manufacturing lots is essential for WHO prequalification. This study aimed to establish the lot-to-lot consistency of a fully liquid, hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)-Haemophilus influenzae b (PRP-T) (DTwP-IPV-HB-PRP∼T) vaccine and to demonstrate non-inferiority to licensed DTwP-HB-PRP∼T and IPV vaccines. Methods: A Phase III, randomized, active-controlled, and open-label study was conducted at multiple centers across India. Healthy infants who had received a birth dose of oral poliovirus vaccine and hepatitis B vaccine received one of three lots of DTwP-IPV-HB-PRP∼T or separate DTwP-HB-PRP∼T and IPV vaccines at 6–8, 10–12, and 14–16 weeks of age. Oral rotavirus vaccine was co-administered at 6–8 weeks of age and 10–12/14–16 weeks of age. DTwP-IPV-HB-PRP∼T lot-to-lot consistency and non-inferiority (pooled DTwP-IPV-HB-PRP∼T) versus DTwP-HB-PRP∼T and IPV post-third dose were assessed using seroprotection rates (anti-D, anti-T, anti-HBs, anti-PRP, anti-polio 1, 2, 3) and adjusted geometric mean concentrations (anti-PT, anti-FIM). Safety was assessed by parental reports. Results: Lot-to-lot consistency was demonstrated for DTwP-IPV-HB-PRP∼T and non-inferiority versus DTwP-HB-PRP∼T and IPV was confirmed with 95% CIs for seroprotection rate differences and adjusted geometric mean concentration ratios within pre-defined clinical margins. Pooled seroprotection rate was ≥ 99.7% for anti-D ≥ 0.01 IU/mL, anti-T ≥ 0.01 IU/mL, anti-HBs ≥ 10 mIU/mL, anti-PRP ≥ 0.15 µg/mL, and anti-polio 1, 2, and 3 ≥ 8 (1/dil) and vaccine response rate was 83.9% for anti-PT and 97.7% for anti-FIM. There were no safety concerns. Conclusions: Immunogenicity of three lots of the fully liquid DTwP-IPV-HB-PRP∼T vaccine was consistent and non-inferior to licensed comparators following vaccination at 6–8, 10–12, and 14–16 weeks of age. There were no safety concerns and no evidence of any effect of co-administration with rotavirus vaccine.

This first in human study was designed as an open label clinical trial to assess the safety and immunogenicity of SIIPL DTwP-HepB-IPV-Hib (Hexavalent) combination vaccine in healthy toddlers, aged 16–24 months. A total of 24 healthy toddlers were administered a 0.5 ml single dose of SIIPL DTwP-HepB-IPV-Hib vaccine intramuscularly, and followed for 28 days for safety outcomes viz. immediate, solicited, unsolicited and serious adverse events. Blood samples were collected immediately prior to and 28 days after vaccination to assess the immunogenicity. Twenty four completed the study in compliance with the study protocol. None of the participants experienced any immediate or any serious adverse event. In terms of the frequency and intensity, the adverse events were comparable to DTwP-based combination vaccines. The vaccine elicited a strong booster response as demonstrated by a large increase in antibodies against all vaccine antigens. One month post booster vaccination seroprotection for diphtheria, tetanus, Hepatitis B, Haemophilus influenzae type b and polio virus type 1 and 3 was 100%. The percentage sero-response for pertussis was 75%. Four-fold increase in antibody concentration for pertussis was achieved in 87.5% subjects. Indigenously developed DTwP-HepB-IPV-Hib vaccine by Serum Institute of India Pvt. Ltd. was found to be safe, well tolerated and showed a robust immune response in toddlers. It was concluded that this vaccine should be assessed in the next phases of clinical development in the target population. Clinical Trial Registration – CTRI/2018/10/015875.

Human immunodeficiency virus (HIV)-exposed infants may be at increased risk of vaccine-preventable disease. This study was conducted as a post-licensure commitment in this population to evaluate the primary series, antibody persistence, and booster response to a licensed fully liquid hexavalent vaccine containing diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), hepatitis B (HB), and Haemophilus influenzae type b antigens (PRP~T). This was a Phase III, open-label, randomized study conducted at a single center in the Republic of South Africa. The DTaP-IPV-HB-PRP~T vaccine was administered to HIV-exposed infected (Group A: N = 14) and HIV-exposed uninfected (Group B: N = 50) infants as a 6, 10, 14 week primary series with a toddler booster at 15–18 months of age. Immunogenicity of each antigen was measured using validated assays and vaccine reactogenicity was recorded using diary cards. The low number of HIV-exposed infected participants, due to widespread pre- and peri-natal retroviral treatment, meant that between-group comparisons should be treated with caution. In each group, primary series and booster immune seroprotection rates were strong, and pre-booster antibody persistence was good, although anti-HBs ≥10 mIU/mL in Group A was 78.6% post-primary series, 58.3% pre-booster, and 75.0% post-booster. There were no safety concerns. In conclusion, primary series and booster vaccination of the DTaP-IPV-HB-PRP~T vaccine were immunogenic and safe in HIV-exposed infected and uninfected infants. These results were comparable to historical data in healthy infants and toddlers.

Background: The combination of whole-cell pertussis (wP) antigens with established diphtheria (D), tetanus (T), hepatitis B (HB), Haemophilus influenzae type b (Hib), and inactivated poliomyelitis (IPV) antigens provides a high-quality DTwP-IPV-HB-PRP∼T vaccine. This study evaluated a DTwP-IPV-HB-PRP∼T booster coadministered with measles, mumps, and rubella (MMR) vaccine. Methods: Phase II, open-label, randomized study. Healthy toddlers who had previously completed a DTwP-IPV-HB-PRP∼T or separate DTwP-HB-PRP∼T and IPV primary vaccination series received a DTwP-IPV-HB-PRP∼T booster vaccine at 12–24 months of age. All participants had also received 1 or 2 doses of measles-containing vaccine between primary vaccination and enrolment (N = 100 and N = 6, respectively). Those who had received 1 prior measles-containing vaccine received an MMR dose either concomitantly (N = 50) or 28 days after (N = 50) the DTwP-IPV-HB-PRP∼T booster. Immunogenicity was evaluated using validated assays and safety by parental reports. Results: Pre-booster vaccination, 100.0% participants showed antibody persistence after DTwP-IPV-HB-PRP∼T or DTwP-HB-PRP∼T and IPV for anti-T (≥0.01 IU/mL), anti-Hib (≥0.15 µg/mL), and anti-polio 3 (≥8 1/dil) and at least 95.8% of participants for anti-D (≥0.01 IU/mL), anti-HB (≥10 mIU/mL), and anti-polio 1 and 2 (≥8 1/dil). For the pertussis antigens, pre-booster antibody persistence (≥2 EU/mL) ranged from 88.6 to 88.7% (anti-PT), 91.4–98.6% (anti-FHA), 69.0–74.3% (anti-PRN), and 97.1–97.2% (anti-FIM). For the booster response, seroprotection based on either the primary series or measles-containing vaccination regimen was 100.0% for anti-D and anti-T (≥0.01 IU/mL and ≥0.10 IU/mL), anti-HB (≥10 mIU/mL and ≥100 mIU/mL), anti-Hib (≥0.15 µg/mL and ≥1 µg/mL) and anti-polio 1, 2, and 3 (≥8 1/dil), and for the pertussis antigens booster response ranged from 88.6 to 91.8% (anti-PT), 91.1–95.9% (anti-FHA), 88.6–93.9% (anti-PRN), and 95.9–98.6% (anti-FIM). There were no safety concerns in any group. Conclusions: This study showed good antibody persistence of the DTwP-IPV-HB-PRP∼T vaccine and good immunogenicity and safety of a booster dose given with MMR in the second year of life.Clinical Trials Registry India Number: CTRI/2018/04/013375.

Introduction Genotoxicity of chemical compounds is primarily associated with the interaction with DNA, formation of mutations, damage to chromosomes and initiating carcinogenesis processes. Currently, many compounds found in the environment are considered to be genotoxic agents, among them chromium: trivalent (III) and hexavalent (VI). The genotoxicity of hexavalent (VI) chromium has been proven in numerous epidemiological, in vitro and in vivo studies. The main source of Cr (VI) is environmental pollution associated with its use in various industries. On the other hand, the role of chromium (III) as a microelement is widely discussed. Due to its beneficial properties, associated with maintaining adequate blood glucose levels and supporting weight loss, it is widely used in the form of dietary supplements, often in doses exceeding the daily requirement. However, the safety of chromium compounds is disputable. Data about the mechanism of genotoxic effects are still incomplete. Objective The aim of this review is to present the current knowledge about the induction of genotoxicity from two forms of chromium: trivalent (III) and hexavalent (VI). State of knowledge Chromium (VI) is a carcinogen with proven mutagenic and genotoxic effects, but this issue is still being investigated by scientists. In recent years, numerous studies have also been conducted on the genotoxic effect of chromium (III). Conclusions Due to the still unexplained mechanism of the genotoxic action and incomplete knowledge about the transformation of chromium in the body, further research is needed, especially due to the growing popularity of Cr (III) compounds and their consumption in the form of dietary supplements and doubts as to the safety of its use, as well as environmental exposure to Cr (VI).

In randomized active-comparator controlled studies, DTaP5-HB-IPV-Hib showed comparable immunogenicity and safety to other licensed vaccines. This study assessed persistence of anti-hepatitis B surface antigen (HBs) and anti-pertussis antibodies, when children were 4 to 5 years of age, 3 to 4 years after initial infant/toddler hexavalent vaccination. This was an extension of 2 European studies in which infants/toddlers received either DTaP5-HB-IPV-Hib or DTaP3-HB-IPV/Hib on a 2 + 1 or 3 + 1 schedule. Primary endpoints included percentages with anti-HBs ≥10 mIU/mL, and anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), anti-pertactin (PRN), and anti-fimbriae types 2 & 3 (FIM) greater than or equal to the lower limit of quantitation (LLOQ). One month after 2 + 1 or 3 + 1 dosing, nearly all toddlers had anti-HBs ≥10 mIU/mL, and responded to the received pertussis antigens. Approximately 3 to 4 years later, 65.8%-70.2% in the DTaP5-HB-IPV-Hib and 82.0%-83.7% in the DTaP3-HB-IPV/Hib groups, respectively, had anti-HBs ≥10 mIU/mL. Percentages of children with pertussis antibodies above LLOQ after 2 + 1 dosing were 58.4% and 41.5% (anti-PT), 80.9% and 88.3% (anti-FHA), 66.1% and 72.6% (anti-PRN), and 94.4% and 3.3% (anti-FIM), in the DTaP5-HB-IPV-Hib and DTaP3-HB-IPV/Hib groups, respectively. This study demonstrated, as expected, waning of hepatitis B and pertussis antibodies during the 3 to 4 years after completion of a 3 + 1 or 2 + 1 hexavalent vaccination schedule. Nonetheless, anti-HBs levels ≥10 IU/mL and detectable antibodies against acellular pertussis antigens persisted in most study participants. The implications of these findings for the long-term prevention of hepatitis B and pertussis are further discussed.

Background: Multivalent vaccines containing whole-cell pertussis (wP) antigens combined with established diphtheria (D), tetanus (T), hepatitis B (HB), Haemophilus influenzae type b (Hib), and inactivated poliomyelitis (IPV) antigens allow the provision of a high-quality, affordable DTwP-IPV-HB-PRP∼T vaccine. Methods: Phase I/II, randomized, active-controlled, open-label study in healthy toddlers (Cohort I) and infants (Cohort II). Toddlers in Cohort I who had completed primary series D, T, P, HB, Hib, and polio vaccination received a booster dose of DTwP-IPV-HB-PRP∼T (N = 30) or DTwP-HB-PRP∼T + IPV (N = 15) vaccines at 15–18 months of age. After satisfactory review of safety data in Cohort I, infants in Cohort II received DTwP-IPV-HB-PRP∼T (N = 100) or DTwP-HB-PRP∼T + IPV (N = 50) at 6–8, 10–12, and 14–16 weeks of age. All infants in Cohort II had received previous oral polio and HB vaccines per country recommendations. Results: Booster and primary series vaccinations were well tolerated with no clinically significant differences between vaccine groups. Most adverse events were mild and resolved spontaneously; there were no vaccine-related serious adverse events and no deaths. In both vaccine groups, anti-D, anti-T, anti-HB, anti-Hib, and anti-polio 1, 2, and 3 seroprotection was 100% post-booster and post-primary series. For the pertussis antigens, booster response rate was > 86% in both groups. For the primary series, vaccine response rate was slightly higher for DTwP-IPV-HB-PRP∼T than DTwP-HB-PRP∼T + IPV for anti-PT (80.2% and 70.8%) and anti-FHA (81.3% and 68.8%), slightly lower for anti-PRN (72.5% and 81.3%), and similar in each group for anti-FIM (95.6% and 97.9%). Conclusions: This study demonstrated a good safety and immunogenicity profile of the hexavalent DTwP-IPV-HB-PRP∼T vaccine for infant primary series vaccination at 6–8, 10–12, and 14–16 weeks of age and booster vaccination at 15–18 months of age and supported progression to the next development phase.

In South Korea, the ready-to-use hexavalent vaccine (against diphtheria, tetanus, pertussis, poliovirus, Haemophilus influenzae type b, and hepatitis B) is not listed despite its facility of no need to reconstitute. It, therefore, has the potential to augment the efficiency of prevention against the six infectious diseases, and it may reduce vaccine-related errors of reconstitution when compared with the currently used vaccination scheme of the pentavalent vaccine with the additional shots against hepatitis B. Given the assumed clinical equivalence between the two vaccination schemes, a cost-minimization analysis has been performed from a societal perspective including all the medical and non-medical direct and indirect costs when vaccinating one birth cohort. The results indicate that the ready-to-use hexavalent vaccine induces a cost reduction of KRW 47,155 (USD36.22) per infant or 12,026 million Korean Won ($9,236,417) in total for the whole birth cohort with 260,500 children. Using the ready-to-use hexavalent vaccine causes a lower infection rate, has fewer vaccination sessions, and may save much time as compared with the current vaccination scheme in place. The ready-to-use hexavalent vaccine may, therefore, benefit the National Immunization Program by reducing the total societal costs of vaccination while improving convenience of infants, parents, and medical care professionals.

Diphtheria-tetanus-pertussis (DTP) combination vaccines are a cornerstone of infant vaccinations worldwide. DTP vaccine acceptance could be impacted by sub-optimal relationships between parents and healthcare professionals (HCPs). This survey, conducted in France and India between 14/2/2020 and 26/3/2020, aimed to understand perspectives and expectations of parents and HCPs toward DTP vaccination. Participants were parents (parents/guardians of ≤3-year-old children; France: n = 1002, India: n = 1021) and HCPs (general practitioners/pediatricians initiating DTP vaccination; France: n = 300; India: n = 300) who chose to take part. A representative sample of parents was achieved via quotas and random iterative weighting to match key demographics of the target population. In India, only parents from socio-economic classes A/B/C and private HCPs were included. Whilst DTP vaccine acceptance was high among parents in France (85%) and India (98%), French HCPs overestimated parental acceptance (99% thought parents were very/fairly accepting). The proportions of parents reporting that the HCP is someone they trust versus the proportions of HCPs wanting to be seen as trusted were discrepant in France (76% versus 90%) but not India (83% versus 85%). Some surveyed parents indicated that, ideally, they would like some input in vaccine brand decisions alongside HCPs, an opinion shared by some HCPs. In France, short-term experience post-vaccination was more important to parents than HCPs, for whom long-term protection was more important. In India, these aspects were equally important to both. Increased awareness of parents’ priorities and concerns regarding DTP vaccination can support HCPs in their discussions with parents and help build trust, which may impact vaccine acceptance.

To evaluate cost implications of a hexavalent vaccine (diphtheria, tetanus, and acellular pertussis [DTaP]–inactivated polio vaccine [IPV]–hepatitis B [HB]– Haemophilus influenzae type B [Hib] polysaccharide conjugated to T protein [PRP∼T]) as an alternative to DT-whole-cell pertussis (wP)–HB//Hib, DTwP, IPV, and oral polio vaccines in the Expanded Program on Immunization schedule in Colombia. Primary vaccination (DTaP–IPV–HB–PRP∼T or DTwP–HB–Hib + IPV [2, 4, 6 months]) and booster (DTaP–IPV–HB–PRP∼T or DTwP + oral polio vaccine [18 months]) (scenario 1) and primary vaccination only (DTaP–IPV–HB–PRP∼T or DTwP–HB–Hib + IPV) (scenario 2) were evaluated. An estimated cost-minimization analysis was based on a micro costing technique for vaccination-associated activities. Adverse event (AE)-associated costs, out-of-pocket costs, and productivity losses for caregivers were included. A budget impact (12-month temporal horizon) was estimated according to the distribution of full-term and premature infants. A 5% annual discount rate was used. A 2-way univariate (tornado) analysis evaluated which variables had the greatest impact on the overall cost. DTaP–IPV–HB–PRP∼T resulted in a cost increase of 29.38% (scenario 1) and 22.19% (scenario 2) for full-term infants and a decrease of 0.99% (scenario 1) and 18.88% (scenario 2) for premature infants, probably because of the higher incidence of wP-related AEs and associated costs in premature infants. With a 100% replacement rate, the budget impact for full-term infants and full-term plus premature infants was 23.73% and 21.80% (scenario 1), respectively, and 13.02% and 11.14% (scenario 2), respectively, of the national immunization program budget. The variables with most impact were the hexavalent vaccine price and costs associated with the pentavalent safety profile. Incorporation of the hexavalent vaccine in the Expanded Program on Immunization schedule would lead to an increase in spending largely mitigated by reduced AE incidence and reduced logistic and social costs. • Currently, diphtheria, tetanus, whole-cell pertussis (DTwP)–hepatitis B (HB)// Haemophilus influenzae type B (Hib), DTwP, inactivated polio vaccine (IPV), and oral polio vaccine (OPV) are used for infant and toddler vaccination in the Expanded Program on Immunization schedule in Colombia. Safety concerns with wP-containing vaccines are well documented, and OPV is associated with a low incidence of vaccine-associated paralytic poliomyelitis and vaccine-derived polioviruses. A fully liquid, hexavalent DT, and acellular pertussis (aP)–IPV–HB–Hib polysaccharide conjugated to tetanus protein (PRP∼T) vaccine that includes aP and IPV antigens, thereby eliminating the safety concerns linked to wP and OPV use, has shown good immunogenicity and safety. Although there is little literature on economic evaluations of the hexavalent vaccine, some studies of cost-effectiveness, cost minimization, or budget impact have been performed in some countries. • Although the safety and immunogenicity of the DTaP–IPV–HB–PRP∼T vaccine are well documented, a robust economic analysis of its implementation is lacking. This study provides the first such analysis of the economic impact of introducing the DTaP–IPV–HB–PRP∼T vaccine in Colombia and includes a comprehensive range of costed variables including logistic and social costs. • The results of this analysis add an economic perspective to support the introduction of the DTaP–IPV–HB–PRP∼T vaccine in the Expanded Program on Immunization schedule in Colombia, complementing established clinical data. The more expensive cost of the DTaP–IPV–HB-PRP∼T vaccine is largely mitigated by reduced costs associated with its better safety profile. The overall difference between the current and proposed schedule is in favor of the DTaP–IPV–HB–PRP∼T vaccine for the primary series in premature infants. [ABSTRACT FROM AUTHOR]

Relevance/aims: Multivalent vaccines are crucial in the control of diseases including diphtheria (D), tetanus (T), pertussis (P), polio, hepatitis B (HB), and Haemophilus influenzae type b (Hib [PRP~T]). To evaluate the safety and immunogenicity of a fully liquid, hexavalent DTaP-IPV-HB-PRP~Tvaccine in infants in the Russian Federation.Materials & methods. Infants (N=100) who had received a standalone HB vaccine within 24 hours after birth and at 1 month of age and a pentavalent (DTaP-IPV/PRP~T) vaccine at 3 and 4.5 months of age were enrolled and received the hexavalent DTaP-IPV-HB-PRP~T vaccine at 6 months of age. Safety was assessed from parental reports and immunogenicity using validated assays.Results. There were no safety concerns, with 38.0% and 49.0% of participants experiencing ≥ 1 solicited injection site and ≥ 1 solicited systemic reaction within 7 days after vaccination, respectively, and 16.0% reporting an unsolicited adverse event (AE) within 30 days after vaccination. The incidence of each solicited reaction with severity Grade 3 was ≤6.0% and all unsolicited AEs were Grade 1 or 2. Most AEs started ≤ 3 days post-vaccination, were short-lived, and resolved spontaneously. There were no serious AEs. On month post-vaccination 100.0% of participants had antibodies ≥ 10 mIU/ mL for anti-HBs, ≥ 0.01 IU/mL for anti-D and anti-T, ≥8 (1/dil) for anti-polio-1,2, 3, and 97.9% of participants had anti-PRP antibodies ≥ 0.15 gg/ml. For anti-PT and anti-FHA, GMCs were in the expected range.Conclusion. These results support vaccination with the DTaP-IPV-HB-PRP~T vaccine in the Russian Federation following the recommended national immunization schedule.

In this work, Bi 2 XO 6 (X = W, Mo) are synthesized at different temperatures. The results of tests find the optimal temperatures of Bi 2 WO 6 and Bi 2 MoO 6 are 180 and 160°C (BW-180, BM-160). Then, BW-180 and BM-160 are further compounded with different contents of CuS. The results of photoelectrochemical (PEC) tests show that CuS can improve the PEC performance of semiconductor materials, and it has better performance when CuS mass fraction is 5%. These maybe the photoelectron potentials generated by CuS/Bi 2 XO 6 (X = Mo, W) heterojunction reduce the combination of photogenerated electrons and holes. When the PEC sensor based on 5%-CuS/BW-180 detects Cr(VI), it has a linear range of 1–80 μmol/L with detection limit of 0.95 μmol/L, while the PEC sensor based on 5%-CuS/BM-160 detects Cr(VI) has a linear range of 0.5–230 μmol/L and a detection limit of 0.12 μmol/L. Thus, 5%-CuS/Bi 2 XO 6 has potential application in hexavalent chromium detection. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Genotoxicity of chemical compounds is primarily associated with the interaction with DNA, formation of mutations, damage to chromosomes and initiating carcinogenesis processes. Currently, many compounds found in the environment are considered to be genotoxic agents, among them chromium: trivalent (III) and hexavalent (VI). The genotoxicity of hexavalent (VI) chromium has been proven in numerous epidemiological, in vitro and in vivo studies. The main source of Cr (VI) is environmental pollution associated with its use in various industries. On the other hand, the role of chromium (III) as a microelement is widely discussed. Due to its beneficial properties, associated with maintaining adequate blood glucose levels and supporting weight loss, it is widely used in the form of dietary supplements, often in doses exceeding the daily requirement. However, the safety of chromium compounds is disputable. Data about the mechanism of genotoxic effects are still incomplete. Objective: The aim of this review is to present the current knowledge about the induction of genotoxicity from two forms of chromium: trivalent (III) and hexavalent (VI). State of knowledge: Chromium (VI) is a carcinogen with proven mutagenic and genotoxic effects, but this issue is still being investigated by scientists. In recent years, numerous studies have also been conducted on the genotoxic effect of chromium (III). Conclusions: Due to the still unexplained mechanism of the genotoxic action and incomplete knowledge about the transformation of chromium in the body, further research is needed, especially due to the growing popularity of Cr (III) compounds and their consumption in the form of dietary supplements and doubts as to the safety of its use, as well as environmental exposure to Cr (VI). [ABSTRACT FROM AUTHOR]

Objective: Antibody persistence evaluation for all antigens of a fully liquid DTaP-IPV-HB-PRP~T vaccine at 3.5 and 4.5 y of age following different primary series and booster schedules in South Africa and Latin America. Methods: Participants had completed one of two previous studies (Study 1-South Africa; Study 2-Latin America). In Study 1, participants who had not received HB vaccine at birth received a 6–10-14 week primary series of DTaP-IPV-HB-PRP~T or DTwP/PRP~T-Hib+HB+OPV and a third group who had received HB vaccine at birth received a 6–10-14 week primary series of DTaP-IPV-HB-PRP~T; all received a booster (15–18 months) of the primary series vaccine(s) except for HB in the DTwP/PRP~T-Hib group. In Study 2, participants received HB vaccine at birth, a 2–4-6 month primary series of DTaP-IPV-HB-PRP~T or DTaP-HB-IPV//PRP~T, and a DTaP-IPV-HB-PRP~T or DTaP-HB-IPV//PRP~T booster (12–24 months). Participants were followed up at 3.5 and 4.5 y of age for antibody persistence. Results: Approximately 80% of eligible participants were assessed. In Study 1, a birth dose of HB increased anti-HBs persistence (≥10 mIU/mL) following DTaP-IPV-HB-PRP~T primary and booster vaccination from 76.3% to 96.1% at 3.5 y of age and from 73.3% to 96.1% at 4.5 y of age; in Study 2, anti-HBs persistence was high and similar in each group. For the other antigens, there were no differences between groups or studies at 3.5 or 4.5 y. Conclusion: Good persistence of antibodies to each antigen in the DTaP-IPV-HB-PRP~T vaccine up to pre-school age, irrespective of the vaccination schedule during the first 2 y of life.

Objective: To evaluate the long-term persistence of anti-hepatitis B surface (HBs) antibodies and the response to a HB challenge re-vaccination in children who had received a primary series of DTaP-IPV-HB-PRP∼T (Hexaxim™) or DTaP-IPV-HB/PRP∼T (Infanrix hexa™). Methods: Two cohorts of participants who had previously received HB vaccine at birth followed by either DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T co-administered with PCV7 at 2, 4, 6 months of age in a randomized, Phase III, observer-blind study in Thailand, were followed up for anti-HBs antibodies (geometric mean concentrations [GMCs] and seroprotection [SP] rate [% of participants with a titer ≥10 mIU/mL]) at 12–18 months of age and 9–10 years of age. A monovalent HB challenge re-vaccination was administered at 9–10 years of age and the anamnestic response was evaluated. Results: Anti-HBs GMCs and SP rates in the DTaP-IPV-HB-PRP∼T and DTaP-IPV-HB/PRP∼T groups were high and similar post-primary vaccination series (2477 mIU/mL and 99.5% and 2442 mIU/mL and 99.5%, respectively) and declined to a similar extent in each group at 12–18 months (154.5 mIU/mL and 90.8% and 162.3 mIU/mL and 96.5%, respectively). Antibody levels further declined at 9–10 years of age (13.3 mIU/mL and 49.3% and 8.0 mIU/mL and 42.9%) and a strong anamnestic response occurred in each group post-HB challenge re-vaccination (92.8% and 98.7%, respectively). Conclusion: The kinetics of long-term anti-HBs antibody persistence were similar following a primary series of DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T. The response to a subsequent HB challenge re-vaccination was strong and similar in each group, demonstrating persisting immune memory.

DTaP-IPV-Hib-HepB is a fully-liquid, hexavalent combination vaccine (Vaxelis™) approved for vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and invasive disease due to Haemophilus influenzae type b (Hib). Hib capsular polysaccharide, polyribosylribitol phosphate (PRP), is conjugated to Neisseria meningitidis outer membrane protein complex (OMPC). Safety and immunogenicity of DTaP-IPV-Hib-HepB were evaluated in 6 Phase III clinical studies including > 5,200 children. Studies included vaccination schedules in the United States (2, 4, 6 months of age) and Europe (2, 3, 4, 12 months of age and 2,4,11–12 months of age). Data pertaining to anti-PRP responses of DTaP-IPV-Hib-Hep B compared to control vaccines from 5 Phase III studies are summarized. Post-infant series, the percentage of participants that achieved protective antibody thresholds for PRP (anti-PRP titer ≥ 0.15 μg/mL and ≥ 1.0 μg/mL, respectively) were higher in DTaP-IPV-Hib-HepB recipients compared to recipients who received control vaccines. A high level of protective responses (96.6% at ≥ 0.15 μg/mL [95% CI:94.8, 97.9%]; 72.9% at ≥ 1.0 μg/mL [95% CI:69.2,76.4%]) were seen post-dose 2 of the 2 + 1 vaccination schedule and met superiority criteria over comparator, p-value < 0.001. In the same schedule, prior to administration of the toddler dose (in the second year of life), anti-PRP titers were higher in DTaP-IPV-Hib-HepB recipients (91.4% at ≥ 0.15 μg/mL; 46.8% at ≥ 1.0 μg/mL) as compared to recipients who received control vaccines (63.4% at ≥ 0.15 μg/mL; 17.1% at ≥ 1.0 μg/mL). One-month post-toddler dose, high levels of anti-PRP titers were achieved in both DTaP-IPV-Hib-HepB recipients (99.8% at ≥ 0.15 μg/mL; 96.6% at ≥ 1.0 μg/mL) and recipients who received control vaccines (99.5% at ≥ 0.15 μg/mL; 94.9% at ≥ 1.0 μg/mL). These results support that DTaP-IPV-Hib-HepB induces a robust and sustained early Hib response. During the high-risk period for Hib disease after the infant vaccine and prior to the toddler dose; >90% of recipients maintained superior protective anti-PRP levels compared to control. [ABSTRACT FROM AUTHOR]

Hypotonic-hyporesponsive (HHE) episodes are known and recognized phenomena, which typically occur within 48 hours of immunisation..Our aim is to describe 12 cases of HHE brought to the Center of Pediatric Sleep Medicine, with attention to the clinical features of the episode and their follow-up. Medical charts of infants visited between 2005–2015 were reviewed. Twelve infants showed a HHE using HHE using Brighton Collaboration Criteria. All infants received a Hexavalent diphtheria -tetanus -pertussis acellular component -hepatitis B-,inactivated poliovirus- Haemophilus influenzae type-b conjugate vaccine. Five out of 12 were brought to Emergency Department, where 2 were symptomatic (one was hyporeactive, the other had fever). No infant died during the episode, or the follow-up, nor developed neurological disease after subsequent vaccinations. HHE are confirmed as benign events, even after administration of hexavalent vaccination, devoid of negative neuropsychomotor outcome.

In Thailand, the hepatitis B (HB) vaccine is administered as a tetravalent vaccine (DTwP-HB) to all infants at 2, 4, and 6 months of age, following an initial vaccination with a monovalent HB vaccine at birth. As part of ongoing vaccine evaluation, we aimed to compare the hepatitis B immunogenicity profiles of children who had received either the pentavalent (DTwP-HB-Hib) or the hexavalent (DTaP-HB-Hib-IPV) vaccine. Two groups of infants, whose mothers previously received the tetanus-diphtheria-acellular pertussis vaccine (Tdap), were randomly vaccinated with either pentavalent or hexavalent vaccine at 2, 4, 6, and 18 months of age, following monovalent HB vaccine at birth. Blood samples were obtained at birth, one-month post-primary series immunization (mo 7), pre-booster (mo 18), one-month post-booster (mo 19), and six months post-booster (mo 24). The third group of infants, whose mothers did not receive Tdap, was vaccinated with DTwP-HB-Hib (EPI pentavalent group). Levels of HBsAg, anti-HBc, and anti-HBs were evaluated by means of an automated Chemiluminescent Microparticle Immunoassay. Anti-HBs levels of ≥10 mIU/ml were achieved in 99.2% (hexavalent group), 99.2% (pentavalent group), and 98.5% (EPI pentavalent group) of infants, after four-dose immunization (at 0, 2, 4, 6 months of age). One month after the additional dose given at 18 months of age, anti-HBs levels of ≥10 mIU/ml were observed in 100% (hexavalent group), 99.2% (pentavalent group), and 93.8% (EPI pentavalent group) of infants. At 24 months of age, higher percentages of infants achieving anti-HBs levels ≥10 mIU/ml were found in the hexavalent group (98.3%) compared to the pentavalent group (86.5%). Both vaccines were effective in inducing anti-HBs levels of ≥10 mIU/ml, and therefore either can be used as a single formula booster at 18 months of age to simplify vaccine administration under the Expanded Program on Immunization in Thailand. [ABSTRACT FROM AUTHOR]

Introduction: Combination vaccines reduce the number of injections received by children, hence improving timeliness and coverage, and general acceptability among caregivers and health-care providers. The most recent hexavalent vaccine, DTaP5-HBV-IPV-Hib, has been also approved by the FDA. Areas covered: DTaP5-HBV-IPV-Hib has demonstrated good immunogenic and safety profiles, not inferior to other hexavalent vaccines already in use in the European market. Either (2p+1/3p+1) immunization schedules can be used with no significant differences. A low incidence of severe adverse events has been shown, similar to other combination vaccines. No issues have arisen when concomitantly administered with other vaccines. Expert opinion: The inclusion of two additional acellular pertussis components (FIM2 and FIM3) might yield better protection against the disease, but this remains to be clinically proven. The new vaccine uses Hib with unique protein carrier (PRP-OMPC) which elicits higher earlier immune response without compromising safety. Compliance with the immunization schedules is expected to increase by decreasing the number of injections needed in combined vaccines for a single visit. In addition, the improvements on the ease-of-use by its liquid-formulation, makes the vaccine preparation more acceptable for use in clinics and may reduce the odds of administration errors. [ABSTRACT FROM AUTHOR]

Introduction: Combination vaccines reduce the ‘shot burden’ and simplify the childhood immunization schedule. Only 5-valent DTaP-based vaccines are licensed in the U.S. Areas covered: A new combination vaccine – DTaP5-IPV-Hib-HepB – is described, which induces antibody responses in infants (given in different schedules, including a 2, 4, and 6-month schedule) that are similar to the respective component vaccines. The vaccine appears to be safe and would be expected to protect against six diseases: diphtheria, tetanus, pertussis, hepatitis B, H influenzae type b, and polio. Administration is associated with higher rates of mild fever, but without significant safety signals. Expert commentary: Incorporation of this hexavalent vaccine into the U.S. schedule could improve coverage rates and timeliness, and addition to the E.U. market would add depth to the available repertoire of combination vaccines.

Translocation between sex-chromosomes and autosomes generates multiple sex-chromosome systems. It happens unexpectedly, and therefore, the evolutionary meaning is not clear. The current study shows a multiple sex chromosome system comprising three different chromosome pairs in a Taiwanese brown frog (Odorrana swinhoana). The male-specific three translocations created a system of six sex-chromosomes, ♂X1Y1X2Y2X3Y3-♀X1X1X2X2X3X3. It is unique in that the translocations occurred among three out of the six members of potential sex-determining chromosomes, which are known to be involved in sex-chromosome turnover in frogs, and the two out of three include orthologs of the sex-determining genes in mammals, birds and fishes. This rare case suggests sex-specific, nonrandom translocations and thus provides a new viewpoint for the evolutionary meaning of the multiple sex chromosome system.

Background: In 2012, Danish authorities submitted a proposal to the European Chemical Agency restricting the content of hexavalent chromium to a maximum of 3 ppm in leather goods. Following its adoption, this proposal was implemented in 2015 as a directive in the EU. Objectives: To examine the temporal trend of chromium contact allergy in adult dermatitis patients patch tested between 2002 and 2017, and to determine clinical characteristics and causative exposures in these patients. Methods: All adult dermatitis patients patch tested between 2002 and 2017 were included. Patch test data were reviewed retrospectively. Comparisons were performed with the χ2 test and logistic regression analysis. Results: A total of 13 379 adults aged 18 to 99 years were patch tested between 2002 and 2017. The overall prevalence of chromium allergy was 2.2%. An overall decreasing trend was found for the prevalence of chromium allergy (Ptrend = 0.00002). Specifically, a significant difference was found for the study periods 2010 to 2013 (Ptrend = 0.002) and 2014 to 2017 (Ptrend < 0.0001) as compared with 2002 to 2005. Leather remained the most important single cause of allergic contact dermatitis caused by chromium. The proportion of clinically relevant leather exposures increased from 42.3% during 2002 to 2009 to 54.8% during 2010 to 2017 (P = 0.04). Conclusions: The prevalence of chromium allergy is decreasing. The EU Directive restricting the use of hexavalent chromium in leather goods is thought to be playing a central role in this change. [ABSTRACT FROM AUTHOR]

Numerous critical reviews have evaluated exposure to toxic and carcinogenic hexavalent chromium (Cr(VI)) from a number of pathways; including workplace air, cement and packaging materials. The contribution of foodstuffs to dietary Cr(VI) has been increasingly under investigation, however no summary of this work has been carried out. The objective of this article is to review the last twenty years of chromium speciation research in foodstuffs. Alkaline extraction, used for chromium speciation in other solids, is the most widely-reported procedure. Previous measurement of Cr(VI) in foodstuffs is questionable due to the reducing power of organic matter and antioxidants, leading to the development of speciated isotope dilution mass spectrometry (SIDMS) techniques to monitor interconversions. Evaluation of the genotoxicity of trivalent chromium (Cr(III)), which acts through a different pathway to that of Cr(VI), requires reconsideration towards measurement of Cr(III), which is present at higher concentrations in foodstuffs following reduction of the more-bioavailable Cr(VI). [ABSTRACT FROM AUTHOR]

Immunogenicity and safety of a newly developed liquid DTwP-Hib/HepB-IPV hexavalent vaccine (EasySix™) was evaluated and compared with administration of commercially licensed Pentavac SD® (DTwP-HepB/Hib) and Imovax Polio® vaccine in an open-label, randomized multi-centric trial. 284 participants, aged 6–10 weeks, randomized in a 1:1 allocation, received three doses of test or comparator vaccines, administered 4 weeks apart. Immunogenicity of the vaccines was determined by measuring the baseline and post-vaccination antibody responses and comparing the proportions of subjects achieving seroprotection against the vaccine antigens; safety was evaluated in terms of solicited (local and systemic) and unsolicited incidences in the follow up phase. Post-vaccination, seroprotection was achieved against all six vaccine antigens in both vaccine groups. The seroresponse rate as well as geometric mean titers of antibody for all vaccine components were comparable between EasySix™ and Pentavac SD®-Imovax Polio® group. Both vaccines had similar reactogenicity profiles and were well tolerated; all adverse events resolved completely without any sequelae. Only one serious adverse event was reported that completely resolved; it was regarded unconnected to the vaccine administered. This study demonstrated that immunogenicity and safety profiles of EasySix™ vaccine, manufactured by Panacea Biotec Ltd, are non-inferior to the commercially available vaccines. Clinical trial registration: CTRI/2015/02/005578 . [ABSTRACT FROM AUTHOR]

Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15-18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPVHB- PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPVHB- PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth. [ABSTRACT FROM AUTHOR]

The analytical method outlined in this feasibility study has been used to show that trivalent chromium (Cr(III)) and hexavalent chromium (Cr(VI)) can be detected and measured in exhaled breath condensate (EBC) samples. EBC samples and urine samples were collected from a cohort of 58 workers occupationally exposed to hexavalent chromium compounds and 22 unexposed volunteers (control group). Levels of Cr(III) and Cr(VI) were determined in EBC samples and total chromium levels were determined in urine samples. Pre and post working week samples for both EBC and urine were collected in tandem. Total chromium in urine samples was analysed by inductively coupled plasma mass spectrometry (ICP-MS). Analysis of Cr(III) and Cr(VI) in EBC samples used a hyphenated micro liquid chromatography (μLC) system coupled to an ICP-MS. Separation was achieved using an anion exchange micro-sized column. The results showed that the occupationally exposed workers had significantly higher levels of Cr(III) and Cr(VI) in their EBC samples than the control group, as well as higher levels of total chromium in their urine samples. However, for the exposed workers no significant difference was found between pre and post working week EBC samples for either Cr(III) or Cr(VI). This study has established that Cr(III) and Cr(VI) can simultaneously be detected and measured in 'real' EBC samples and will help in understanding inhalation exposure. [ABSTRACT FROM AUTHOR]

The DOCK-AND-LOCKTM (DNLTM) method provides a modular approach to develop multivalent, multifunctional complexes of defined structures, of which bispecific hexavalent antibodies (bsHexAbs) are prominent examples with potential applications in targeted therapy for malignant, autoimmune, and infectious diseases. Currently, bsHexAbs are constructed by derivatizing a divalent IgG, at the carboxyl termini of either the heavy chain (the CH3-format) or the light chain (the Ck-format), to contain two stabilized dimers of Fab having a different specificity from the IgG. In this review, we briefly outline the features of the DNLTM method and describe key aspects of bsHexAbs examined with diverse preclinical studies, which include binding affinity to target cells, induction of signaling pathways, effector functions, serum stability, pharmacokinetics, and antitumor activity in human tumor xenograft models. Our findings favor the selection of the CK- over the CH3-format for further exploration of bsHexAbs in clinical trials.

Introduction & Objective: Industrial wastewaters including heavy metals, are one of the important sources of environmental pollution. Heavy metals such as chromium is found in plating wastewater and is harmful for human health and environment. The purpose of the present study was to investigate adsorption of hexavalent chromium Cr (VI) from aqueous solution onto commerical Iron powder as an effective, faster ,and cheaper adsorbent. Materials & Methods: This research was an experimental- lablatory study done in batch system. This study investigated the removal of hexavalent chromium by using commerical Iron powder with variation pH, contact time, Iron powder dose and initial hexavalent chromium concentration in batch system , and the result was analyzed by Excel software. Results: The results showed that the removal efficiency decreased with increasing pH and initial chromium concentration. Also the results showed that the removal efficiency increased with increasing Iron powder dose and contact time. With increasing adsorbent dose from 0.1g/100cc to 1.5 g/100cc, the removal efficiency increased from 47.5% to 92.5 % in constant conditions (pH=7, initial hexavalent chromium concentration = 20 mg/L ). Also removal efficiency increased from 41.1% to 48.5% with increasing contact time from 2 min to 120 min in constant conditions (pH=7, Iron powder= 0.1g/100cc, initial hexavalent chromium concentration= 20 mg/L). Experimental isotherms and kinetics models were assessed by Langmuir and Freundlich isotherms and pseudo-first-order, pseudo-second-order kinetics and modifed pseudo-first-order models. The results showed that the data were acceptably explained by Langmuir isotherms and pseudo-second-order kinetics models, respectively. Conclusion: The results showed that the removal of hexavalent chromium from aqueous solution using sawdust can be done faster and cheaper.

Introduction:Combination vaccines reduce the ‘shot burden’ and simplify the childhood immunization schedule. Only 5-valent DTaP-based vaccines are licensed in the U.S. Areas covered:A new combination vaccine – DTaP5-IPV-Hib-HepB – is described, which induces antibody responses in infants (given in different schedules, including a 2, 4, and 6-month schedule) that are similar to the respective component vaccines. The vaccine appears to be safe and would be expected to protect against six diseases: diphtheria, tetanus, pertussis, hepatitis B, H influenzae type b, and polio. Administration is associated with higher rates of mild fever, but without significant safety signals. Expert commentary:Incorporation of this hexavalent vaccine into the U.S. schedule could improve coverage rates and timeliness, and addition to the E.U. market would add depth to the available repertoire of combination vaccines. [ABSTRACT FROM PUBLISHER]

DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants. This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46–74 days (n = 350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n = 175) or without MenC vaccine (Group 2; n = 175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines. The proportion of participants with an anti-HBs concentration ⩾10 mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1–99.3] in the coadministration group and 96.1% [95%CI: 91.8–98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved. Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups. ClinicalTrials.gov identifier: NCT01839175 ; EudraCT number: 2012-005547-24. [ABSTRACT FROM AUTHOR]

Background Combination vaccines simplify vaccination visits and improve coverage and timeliness. DTaP5-HB-IPV-Hib is a new investigational, fully-liquid, combination vaccine designed to protect against 6 infectious diseases, including 5 pertussis antigens and OMPC instead of PT as conjugated protein for Hib component. Methods In this multicenter, double-blind, comparator-controlled, Phase III study (NCT01480258) conducted in Sweden, Italy, and Finland, healthy infants were randomized 1:1 to receive one two immunization regimens. The DTaP5-HB-IPV-Hib Group received the investigational hexavalent vaccine (DTaP5-HB-IPV-Hib) and the Control Group received Infanrix-hexa (DTPa3-HBV-IPV/Hib) at 2, 4 and 11–12 months of age. Both groups received concomitantly Prevnar 13 (PCV13) and Rotateq (RV5) or Rotarix (RV1) at 2, 4 months of age and PCV13 at 11–12 months. Subjects administered RV5 received a 3rd dose at 5 months of age. Results A total of 656 subjects were randomized to the DTaP5-HB-IPV-Hib Group and 659 subjects to Control Group. Immune responses to all vaccine antigens post-toddler dose were non-inferior in the DTaP5-HB-IPV-Hib Group as compared to the Control Group. Additionally, the post-dose 2 and pre-toddler DTaP5-HB-IPV-Hib anti-PRP responses were superior. The DTaP5-HB-IPV-Hib Group responses to concomitant RV1 were non-inferior compared to the Control Group. Solicited adverse event rates after any dose were similar in both groups, except for higher rates of pyrexia (6.4% difference; 95% CI: 1.5, 11.3) and somnolence (5.8% difference; 95% CI: 1.7, 9.8) in the DTaP5-HB-IPV-Hib Group. Vaccine-related serious adverse events occurred infrequently in the DTaP5-HB-IPV-Hib Group (0.3%) and the Control Group (0.5%). Conclusions The safety and immunogenicity of DTaP5-HB-IPV-Hib is generally comparable to Control when administered in the 2, 4, 11–12 month schedule. Early Hib responses were superior versus Control. DTaP5-HB-IPV-Hib could provide a new hexavalent option for pediatric combination vaccines, aligned with recommended immunizations in Europe. Study identification: V419-008 CLINICALTRIALS.GOV identifier: NCT01480258 [ABSTRACT FROM AUTHOR]

A non-linear approach, consistent with available mode of action (MOA) data, is most scientifically defensible for assessing the carcinogenicity of oral exposure to hexavalent chromium (CrVI). Accordingly, the current paper builds upon previous studies (Haney, 2015a, 2015b) to first develop a non-linear, non-threshold approach as well as a non-linear threshold approach for assessing the oral carcinogenicity of CrVI, and then utilizes available MOA analyses and information for selection of the most scientifically-supported approach. More specifically, a non-linear, non-threshold dose–response function was developed that adequately describes the non-linearity predicted for potential human excess risk versus oral dose due to the sub-linear relationship between oral dose and internal dose (added mg Cr/kg target tissue) across environmentally-relevant doses of regulatory interest. Additionally, benchmark dose modeling was used to derive a reference dose (RfD of 0.003 mg/kg-day) with cytotoxicity-induced regenerative hyperplasia as a key precursor event to carcinogenesis in the mouse small intestine. This RfD value shows remarkable agreement with that published previously (0.006 mg/kg-day) based on a more scientifically-sophisticated, physiologically-based pharmacokinetic modeling approach (Thompson et al., 2013b). The RfD approach is the most scientifically-defensible approach based on the weight-of-evidence of available MOA information and analyses conducted for the most scientifically-supported MOA. [ABSTRACT FROM AUTHOR]

Trivalent chromium compounds are used for leather tanning, and chromium may be released during use of leather goods. In certain instances, small amounts of hexavalent chromium can be formed and released. Both trivalent and hexavalent chromium can elicit allergic skin reaction in chromium sensitised subjects, the latter being significantly more potent. Induction of sensitisation only occurs after exposure to hexavalent chromium. A minority of subjects are sensitised to chromium, and in a fraction of these subjects allergic skin reaction have been described after wearing leather shoes or, less frequently, other leather goods. The evidence that in all these cases the reaction is related to hexavalent chromium is not always strong. The content of hexavalent chromium in leather is regulated in European Union, but rate of release rather than content is relevant for allergic skin reaction. The role of trivalent chromium appear much less relevant if at all. Modern tanning procedure do not pose significant risk due to either hexavalent or trivalent chromium. Dismissing bad quality and worn-off leather goods is relevant in reducing or eliminating the skin reaction. It should also be pointed out that shoe components or substances other than chromium in leather may cause allergic/irritative skin reactions. [ABSTRACT FROM AUTHOR]

Dose-dependent changes in target tissue absorption have important implications for determining the most defensible approach for developing a cancer-based oral toxicity factor for hexavalent chromium (CrVI). For example, mouse target tissue absorption per unit dose is an estimated 10-fold lower at the CrVI dose corresponding to the federal maximum contaminant level (MCL) than at the USEPA draft oral slope factor (SFo) point of departure dose. This decreasing target tissue absorption as doses decrease to lower, more environmentally-relevant doses is inconsistent with linear low-dose extrapolation. The shape of the dose–response curve accounting for this toxicokinetic phenomenon would clearly be non-linear. Furthermore, these dose-dependent differences in absorption indicate that the magnitude of risk overestimation by a linear low-dose extrapolation approach (e.g., SFo) increases and is likely to span one or perhaps more orders of magnitude as it is used to predict risk at progressively lower, more environmentally-relevant doses. An additional apparent implication is that no single SFo can reliably predict risk across potential environmental doses (e.g., doses corresponding to water concentrations ⩽ the federal MCL). A non-linear approach, consistent with available mode of action data, is most scientifically defensible for derivation of an oral toxicity factor for CrVI-induced carcinogenesis. [ABSTRACT FROM AUTHOR]

The mouse dose at the lowest water concentration used in the National Toxicology Program hexavalent chromium (CrVI) drinking water study (NTP, 2008) is about 74,500 times higher than the approximate human dose corresponding to the 35-city geometric mean reported in EWG (2010) and over 1000 times higher than that based on the highest reported tap water concentration. With experimental and environmental doses differing greatly, it is a regulatory challenge to extrapolate high-dose results to environmental doses orders of magnitude lower in a meaningful and toxicologically predictive manner. This seems particularly true for the low-dose extrapolation of results for oral CrVI-induced carcinogenesis since dose-dependent differences in the dose fraction absorbed by mouse target tissues are apparent (Kirman et al., 2012). These data can be used for a straightforward adjustment of the USEPA (2010) draft oral slope factor (SFo) to be more predictive of risk at environmentally-relevant doses. More specifically, the evaluation of observed and modeled differences in the fraction of dose absorbed by target tissues at the point-of-departure for the draft SFo calculation versus lower doses suggests that the draft SFo be divided by a dose-specific adjustment factor of at least an order of magnitude to be less over-predictive of risk at more environmentally-relevant doses. [ABSTRACT FROM AUTHOR]