IMPORTANCE: Maternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine could prevent infant pertussis. OBJECTIVE: To evaluate the safety and ...immunogenicity of Tdap immunization during pregnancy and its effect on infant responses to diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine. DESIGN, SETTING, AND PARTICIPANTS: Phase 1-2, randomized, double-blind, placebo-controlled, clinical trial conducted from 2008 to 2012. Forty-eight pregnant women aged 18 to 45 years received Tdap (n = 33) or placebo (n = 15) at 30 to 32 weeks’ gestation, with crossover immunization postpartum. INTERVENTIONS: Tdap vaccination at 30 to 32 weeks’ gestation or postpartum. MAIN OUTCOMES AND MEASURES: Primary outcomes were maternal and infant adverse events, pertussis illness, and infant growth and development until age 13 months. Secondary outcomes were antibody concentrations in pregnant women before and 4 weeks after Tdap immunization or placebo, at delivery and 2 months’ postpartum, and in infants at birth, at 2 months, and after the third and fourth doses of DTaP. RESULTS: No Tdap-associated serious adverse events occurred in women or infants. Injection site reactions after Tdap immunization were reported in 26 (78.8% 95% CI, 61.1%-91.0%) and 12 (80% 95% CI, 51.9%-95.7%) pregnant and postpartum women, respectively (P > .99). Systemic symptoms were reported in 12 (36.4% 95% CI, 20.4%-54.9%) and 11 (73.3% 95% CI, 44.9%-92.2%) pregnant and postpartum women, respectively (P = .03). Growth and development were similar in both infant groups. No cases of pertussis occurred. Significantly higher concentrations of pertussis antibodies were measured at delivery in women who received Tdap during pregnancy vs postpartum (eg, pertussis toxin antibodies: 51.0 EU/mL 95% CI, 37.1-70.1 and 9.1 EU/mL 95% CI, 4.6-17.8, respectively; P < .001) and in their infants at birth (68.8 EU/mL 95% CI, 52.1-90.8 and 14.0 EU/mL 95% CI, 7.3-26.9, respectively; P < .001) and at age 2 months (20.6 EU/mL 95% CI, 14.4-29.6 and 5.3 EU/mL 95% CI, 3.0-9.4, respectively; P < .001). Antibody responses in infants born to women receiving Tdap during pregnancy were not different following the fourth dose of DTaP. CONCLUSIONS AND RELEVANCE: This preliminary assessment did not find an increased risk of adverse events among women who received Tdap vaccine during pregnancy or their infants. For secondary outcomes, maternal immunization with Tdap resulted in high concentrations of pertussis antibodies in infants during the first 2 months of life and did not substantially alter infant responses to DTaP. Further research is needed to provide definitive evidence of the safety and efficacy of Tdap immunization during pregnancy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00707148
Abstract Globally, group B Streptococcus (GBS) remains a leading cause of sepsis and meningitis in infants in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at ...increased risk of transmitting GBS to their newborns has been effective in reducing part, but not all, of the GBS disease burden in many high income countries (HICs). In low- and middle-income countries (LMICs), IAP use is low. Immunization of pregnant women with a GBS vaccine represents an alternative strategy to protecting newborns and young infants, through transplacental antibody transfer and potentially by reducing new vaginal colonization. This vaccination strategy was first suggested in the 1970s and several potential GBS vaccines have completed phase I/II clinical trials. During the 2015 WHO Product Development for Vaccines Advisory Committee meeting, GBS was identified as a high priority for the development of a vaccine for maternal immunization because of the major public health burden posed by GBS in LMICs, and the high technical feasibility for successful development. Following this meeting, the first WHO technical consultation on GBS vaccines was held on the 27th and 28th of April 2016, to consider development pathways for such vaccines, focused on their potential role in reducing newborn and young infant deaths and possibly stillbirths in LMICs. Discussion topics included: (1) pathophysiology of disease; (2) current gaps in the knowledge of global disease burden and serotype distribution; (3) vaccine candidates under development; (4) design considerations for phase III trials; and (5) pathways to licensure, policy recommendations and use. Efforts to address gaps identified in each of these areas are needed to establish the public health need for, the development and deployment of, efficacious GBS vaccines. In particular, more work is required to understand the global disease burden of GBS-associated stillbirths, and to develop quality-assured standardized antibody assays to identify correlates of protection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Survivors of infant group B streptococcal (GBS) disease are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified. This is the 10th of 11 articles ...estimating the burden of GBS disease. Here we aimed to estimate NDI in survivors of infant GBS disease.
We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature LILACS, World Health Organization Library Information System WHOLIS, and Scopus) and sought unpublished data on the risk of NDI after invasive GBS disease in infants <90 days of age. We did meta-analyses to derive pooled estimates of the percentage of infants with NDI following GBS meningitis.
We identified 6127 studies, of which 18 met eligibility criteria, all from middle- or high-income contexts. All 18 studies followed up survivors of GBS meningitis; only 5 of these studies also followed up survivors of GBS sepsis and were too few to pool in a meta-analysis. Of meningitis survivors, 32% (95% CI, 25%-38%) had NDI at 18 months of follow-up, including 18% (95% CI, 13%-22%) with moderate to severe NDI.
GBS meningitis is an important risk factor for moderate to severe NDI, affecting around 1 in 5 survivors. However, data are limited, and we were unable to estimate NDI after GBS sepsis. Comparability of studies is difficult due to methodological differences including variability in timing of clinical reviews and assessment tools. Follow-up of clinical cases and standardization of methods are essential to fully quantify the total burden of NDI associated with GBS disease, and inform program priorities.
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Group B Streptococcus (GBS) remains a leading cause of neonatal sepsis in high-income contexts, despite declines due to intrapartum antibiotic prophylaxis (IAP). Recent evidence suggests higher ...incidence in Africa, where IAP is rare. We investigated the global incidence of infant invasive GBS disease and the associated serotypes, updating previous estimates.
We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature LILACS, World Health Organization Library Information System WHOLIS, and Scopus) and sought unpublished data regarding invasive GBS disease in infants aged 0-89 days. We conducted random-effects meta-analyses of incidence, case fatality risk (CFR), and serotype prevalence.
We identified 135 studies with data on incidence (n = 90), CFR (n = 64), or serotype (n = 45). The pooled incidence of invasive GBS disease in infants was 0.49 per 1000 live births (95% confidence interval CI, .43-.56), and was highest in Africa (1.12) and lowest in Asia (0.30). Early-onset disease incidence was 0.41 (95% CI, .36-.47); late-onset disease incidence was 0.26 (95% CI, .21-.30). CFR was 8.4% (95% CI, 6.6%-10.2%). Serotype III (61.5%) dominated, with 97% of cases caused by serotypes Ia, Ib, II, III, and V.
The incidence of infant GBS disease remains high in some regions, particularly Africa. We likely underestimated incidence in some contexts, due to limitations in case ascertainment and specimen collection and processing. Burden in Asia requires further investigation.
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Early-onset group B streptococcal disease (EOGBS) occurs in neonates (days 0-6) born to pregnant women who are rectovaginally colonized with group B Streptococcus (GBS), but the risk of EOGBS from ...vertical transmission has not been systematically reviewed. This article, the seventh in a series on the burden of GBS disease, aims to estimate this risk and how it varies with coverage of intrapartum antibiotic prophylaxis (IAP), used to reduce the incidence of EOGBS.
We conducted systematic reviews (Pubmed/Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), World Health Organization Library Information System WHOLIS, and Scopus) and sought unpublished data from investigator groups on maternal GBS colonization and neonatal outcomes. We included articles with ≥200 GBS colonized pregnant women that reported IAP coverage. We did meta-analyses to determine pooled estimates of risk of EOGBS, and examined the association in risk of EOGBS with IAP coverage.
We identified 30 articles including 20328 GBS-colonized pregnant women for inclusion. The risk of EOGBS in settings without an IAP policy was 1.1% (95% confidence interval CI, .6%-1.5%). As IAP increased, the risk of EOGBS decreased, with a linear association. Based on linear regression, the risk of EOGBS in settings with 80% IAP coverage was predicted to be 0.3% (95% CI, 0-.9).
The risk of EOGBS among GBS-colonized pregnant women, from this first systematic review, is consistent with previous estimates from single studies (1%-2%). Increasing IAP coverage was linearly associated with decreased risk of EOGBS disease.
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Preterm birth complications are the leading cause of deaths among children <5 years of age. Studies have suggested that group B Streptococcus (GBS) maternal rectovaginal colonization during pregnancy ...may be a risk factor for preterm delivery. This article is the fifth of 11 in a series. We aimed to assess the association between GBS maternal colonization and preterm birth in order to inform estimates of the burden of GBS.
We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature LILACS, World Health Organization Library Information System WHOLIS, and Scopus) and sought unpublished data from investigator groups on the association of preterm birth (<37 weeks' gestation) and maternal GBS colonization (GBS isolation from vaginal, cervical, and/or rectal swabs; with separate subanalysis on GBS bacteriuria). We did meta-analyses to derive pooled estimates of the risk and odds ratios (according to study design), with sensitivity analyses to investigate potential biases.
We identified 45 studies for inclusion. We estimated the risk ratio (RR) for preterm birth with maternal GBS colonization to be 1.21 (95% confidence interval CI, .99-1.48; P = .061) in cohort and cross-sectional studies, and the odds ratio to be 1.85 (95% CI, 1.24-2.77; P = .003) in case-control studies. Preterm birth was associated with GBS bacteriuria in cohort studies (RR, 1.98 95% CI, 1.45-2.69; P < .001).
From this review, there is evidence to suggest that preterm birth is associated with maternal GBS colonization, especially where there is evidence of ascending infection (bacteriuria). Several biases reduce the chance of detecting an effect. Equally, however, results, including evidence for the association, may be due to confounding, which is rarely addressed in studies. Assessment of any effect on preterm delivery should be included in future maternal GBS vaccine trials.
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Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic organic fluoro-compounds that are oil-, water-, and flame-resistant, making them useful in a wide range of commercial and ...consumer products, as well as resistant to environmental degradation. To assess the impact of urbanization and wastewater treatment processes, surface water and sediment samples were collected at 27 sites within the Great Lakes in the Lake Huron to Lake Erie corridor (HEC), an international waterway including the highly urbanized Detroit and Rouge Rivers. Samples were analyzed for 92 PFAS via UHPLC-MS/MS. Our previous data in the HEC found the highest amount of PFAS contamination at the Rouge River mouth. In addition to evaluating the input of the Rouge River into the HEC, we evaluated the transport of PFAS into the HEC from other major tributaries. PFAS were detected in both surface water and sediment at all sites in this study, with a total of 10 congeners quantified in all surface water samples and 16 congeners quantified in all sediment samples, indicating ubiquitous contamination. Perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were pervasive in the HEC as these two compounds were detected in all sites and matrices, often at concentrations above the US EPA's recommended lifetime interim updated health advisories. Surface water samples contained more perfluorohexanoic acid (PFHxA) than any other congener, with average aqueous PFHxA across all surface water samples exceeding the average concentration previously reported in the Great Lakes. Sediment samples were dominated by PFOS, but novel congeners, notably 3-Perfluoropentyl propanoic acid (FPePA), were also quantified in sediment. The Rouge River and other tributaries contribute significantly to the PFAS burden in the HEC including Lake Erie. Overall, our results indicate the need for expanding toxicological research and risk assessment focused on congeners such as PFHxA and PFAS mixtures, as well as regulation that is tighter at the onset of production and encompasses PFAS as a group at a national level.
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•Higher PFAS burdens are found in tributaries compared to receiving waters.•92-PFAS LC-MS method quantified novel congeners not previously reported this region.•Rouge River watershed greatly contributes to PFAS burden in Huron Erie corridor.•PFHxA was the PFAS with the highest cumulative concentration in all water samples.•Legacy PFOS and PFOA persist in sediment and water in the HEC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background. In 2006, the Advisory Committee on Immunization Practices recommended tetanus, diphtheria, acellular pertussis (Tdap) vaccination of all caregivers of infants aged <1 year ("cocooning") ...to prevent pertussis-related complications and deaths. We implemented cocooning in a predominantly Hispanic, medically underserved, uninsured population at a Houston hospital. Phase 1 (January 2008–January 2010) provided maternal postpartum Tdap vaccine; Phase 2 (June 2009–January 2010) also vaccinated infant contacts on-site. Methods. Pertussis education was provided to health care personnel and mothers. Standing orders for maternal postpartum Tdap vaccination were initiated. Mothers were interviewed to ascertain the number of additional infant contacts eligible to receive Tdap vaccine. Consenting eligible contacts received Tdap vaccine as soon as possible after delivery. Results. From 7 January 2008 through 31 January 2010, 8334 (75%) of 11,174 postpartum women received Tdap vaccine. During Phase 2, 2969 (86%) of 3455 postpartum women were vaccinated; another 197 (6%) had previously received Tdap vaccine. Mothers were Hispanic (91.4%), black (5.4%), white (0.8%), Asian (1.4%) and other (1.0%). A median of 3 (range, 1–11) other Tdap-eligible contacts per infant were identified, and a median of 2 (range, 0–10) contacts per infant received Tdap vaccine. Of 1860 contacts vaccinated, 1813 (98%) anticipated daily infant contact. A total of 1697 (91%) received Tdap vaccine before infant hospital discharge, and 144 (8%) received Tdap vaccine within 7 days after hospital discharge. Barriers to full cocooning included the need for extended vaccination hours, visiting restrictions because of pandemic H1N1 influenza, and inaccurate recall of vaccination history. Conclusion. Although practical and logistical barriers exist, Tdap cocooning was well accepted by and successfully implemented in a high-risk population by using standing orders and providing vaccinations on-site.
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