PMID: 

Vaccine. 2016 12 7 ;34(50):6172-6180. Epub 2016 Nov 10. PMID: 27840013

Abstract Title: 

Simultaneous vaccination with MMR and DTaP-IPV-Hib and rate of hospital admissions with any infections: A nationwide register based cohort study.

Abstract: 

BACKGROUND: In Denmark, live measles, mumps, and rubella vaccine (MMR) is associated with a reduced risk of infectious disease admissions, particularly for lower respiratory tract infections. In low-income countries, simultaneous vaccination (i.e. vaccination at the same visit) with live and inactivated vaccines may increase child mortality compared with the live vaccine alone. We examined the hypothesis that simultaneous administration of MMR and the inactivated DTaP-IPV-Hib vaccine compared with MMR alone is associated with higher incidence of infectious disease admissions.METHODS: Nationwide, retrospective, register based cohort study of 520,859 children born in Denmark 1997-2006, who were followed from 15months to 4years of age. Incidence rate ratios (IRRs) of hospital admissions were estimated by Cox regression and adjusted for background factors including exact age.RESULTS: By 2years of age, 4965 children had simultaneous MMR and DTaP-IPV-Hib as their most recent vaccination. Compared with MMR alone, simultaneous administration was associated with a higher rate of lower respiratory tract infections (adjusted incidence rate ratio (IRR), 1.27; 95% confidence interval (CI), 1.13-1.42). There was no effect on other infections. Overall, simultaneous administration was associated with a 7% (95% CI, 0-15%) increase in infectious disease admissions.CONCLUSIONS: Simultaneous administration of MMR and DTaP-IPV-Hib compared with MMR alone may increase the rate of hospital admissions related to lower respiratory tract infections. These findings require replication in other high-income settings.

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PMID: 

Metabolism. 2019 Nov ;100S:153944. PMID: 31610849

Abstract Title: 

Fine particle environmental pollution and cardiovascular diseases.

Abstract: 

Air pollution affects 90% of the world's population and has caused 9 million deaths in 2015, becoming the most important cause of premature deaths in the world. Exposure to fine particulate matter, a major component of urban air pollution, has been associated with an increase in cardiovascular risk and associated mortality. Impact of fine particles on the cardiovascular system includes inflammation, activation of prothrombotic pathways, oxidative stress, vascular dysfunction and remodeling, and neurological dysfunction. Genetic and epigenetic factors might also increase the susceptibility to air pollution. Consequently, epidemiologic studies have identified correlations between air particulate matter concentrations and acute coronary events, ischemic cardiomyopathy, acute heart failure, and stroke. Interestingly, these effects are present even for fine particulate matter concentrations below current US and EU regulatory standards, and seems to be more harmful in the most fragile population such as low-income or elderly subjects, or patients with previous cardiovascular disease. This review aims to summarize recent data on the pathophysiology and epidemiology of cardiovascular disease after particulate matter exposure. It will also discuss potential strategies to reduce the impact of air pollution on current and future populations' health.

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PMID: 

Toxicol Pathol. 2019 Dec ;47(8):976-992. Epub 2019 Oct 14. PMID: 31610749

Abstract Title: 

The Impact of Inhaled Ambient Ultrafine Particulate Matter on Developing Brain: Potential Importance of Elemental Contaminants.

Abstract: 

Epidemiological studies report associations between air pollution (AP) exposures and several neurodevelopmental disorders including autism, attention deficit disorder, and cognitive delays. Our studies in mice of postnatal (human third trimester brain equivalent) exposures to concentrated ambient ultrafine particles (CAPs) provide biological plausibility for these associations, producing numerous neuropathological and behavioral features of these disorders, including male-biased vulnerability. These findings raise questions about the specific components of AP that underlie its neurotoxicity, which our studies suggest could involve trace elements as candidate neurotoxicants. X-ray fluorescence analyses of CAP chamber filters confirm contamination of AP exposures by multiple elements, including iron (Fe) and sulfur (S). Correspondingly, laser ablation inductively coupled plasma mass spectrometry of brains of male mice indicates marked postexposure elevations of Fe and S and other elements. Elevations of brain Fe and S in particular are consistent with potential ferroptotic, oxidative stress, and altered antioxidant capacity-based mechanisms of CAPs-induced neurotoxicity, supported by observations of increased serum oxidized glutathione and increased neuronal cell death in nucleus accumbens with no corresponding significant increase in caspase-3, in male brains following postnatal CAP exposures. Understanding the role of trace element contaminants of particulate matter AP as a source of neurotoxicity is critical for public health protection.

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PMID: 

PLoS Pathog. 2017 01 ;13(1):e1006117. Epub 2017 Jan 19. PMID: 28103317

Abstract Title: 

Genetically Thermo-Stabilised, Immunogenic Poliovirus Empty Capsids; a Strategy for Non-replicating Vaccines.

Abstract: 

While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated) vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer. However it is known that the Sabin vaccine strains are genetically unstable and can revert to a virulent transmissible form. A possible solution to the need for virus growth would be to generate empty viral capsids by recombinant technology, but hitherto such particles are so unstable as to be unusable. We report here the genetic manipulation of the virus to generate stable empty capsids for all three serotypes. The particles are shown to be extremely stable and to generate high levels of protective antibodies in animal models.

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PMID: 

J Investig Med. 2019 Oct 16. Epub 2019 Oct 16. PMID: 31619486

Abstract Title: 

Association between coarse particulate matter (PM) and nasopharyngeal carcinoma among Taiwanese men.

Abstract: 

The nasopharyngeal tract traps mainly coarse particles in inhaled air. Soluble carcinogenic compounds, endotoxins, and trace metals contained in these particles are potential causes of inflammation and oxidative stress which could enhance carcinogenesis. The aim of this study was to determine the association between coarse particulate matter (PM) and nasopharyngeal cancer (NPC). A total of 521,098 men (355 cases and 520,743 non-cases), aged≥40 years were included in this study. Data were retrieved from the Taiwan Cancer Registry, the Adult Preventive Medical Services Database, and the Air Quality Monitoring Database. PMwas significantly associated with a higher risk of NPC after adjusting for SO, NOx, O, age, body mass index, smoking, alcohol drinking, betel nut chewing, exercise, hypertension, diabetes, and hyperlipidemia. With PM

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PMID: 

Lancet Infect Dis. 2017 07 ;17(7):745-753. Epub 2017 Apr 25. PMID: 28454674

Abstract Title: 

Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants

Abstract: 

BACKGROUND: Cost and supply constraints are key challenges in the use of inactivated polio vaccine (IPV). Dose reduction through adsorption to aluminium hydroxide (Al) is a promising option, and establishing its effectiveness in the target population is a crucial milestone in developing IPV-Al. The aim of this clinical trial was to show the non-inferiority of three IPV-Al vaccines to standard IPV.METHODS: In this phase 2, non-inferiority, observer-blinded, randomised, controlled, single-centre trial in the Dominican Republic, healthy infants aged 6 weeks, not previously polio vaccinated, were allocated after computer-generated randomisation by block-size of four, to receive one of four IPV formulations (three-times reduced dose [1/3 IPV-Al], five-times reduced dose [1/5 IPV-Al], ten-times reduced dose [1/10 IPV-Al], or IPV) intramuscularly in the thigh at 6, 10, and 14 weeks of age. The primary outcome was seroconversion for poliovirus types 1, 2, and 3 with titres more than or equal to four-fold higher than the estimated maternal antibody titre and more than or equal to 8 after three vaccinations. Non-inferiority was concluded if the lower two-sided 90% CI of the seroconversion rate difference between IPV-Al and IPV was greater than -10%. The safety analyses were based on the safety analysis set (randomly assigned participants who received at least one trial vaccination) and the immunogenicity analyses were based on the per-protocol population. This study is registered with ClinicalTrials.gov registration, number NCT02347423.FINDINGS: Between Feb 2, 2015, and Sept 26, 2015, we recruited 824 infants. The per-protocol population included 820 infants; 205 were randomly assigned to receive 1/3 IPV-Al, 205 to receive 1/5 IPV-Al, 204 to receive 1/10 IPV-Al, and 206 to receive IPV. The proportion of individuals meeting the primary endpoint of seroconversion for poliovirus types 1, 2, and 3 was already high for the three IPV-Al vaccines after two vaccinations, but was higher after three vaccinations (ie, after completion of the expanded programme of immunisation schedule): 1/3 IPV-Al 98·5% (n=202, type 1), 97·6% (n=200; type 2), and 99·5% (n=204, type 3); 1/5 IPV-Al: 99·5% (n=204, type 1), 96·1% (n=197, type 2), and 98·5% (n=202, type 3); and 1/10 IPV-Al: 98·5% (n=201, type 1), 94·6% (n=193, type 2), and 99·5% (n=203, type 3). All three IPV-Al were non-inferior to IPV, with absolute differences in percentage seroconversion for each poliovirus type being greater than -10% (1/3 IPV-Al type 1, -1·46 [-3·60 to 0·10], type 2, -0·98 [-3·62 to 1·49], and type 3, -0·49 [-2·16 to 0·86]; 1/5 IPV-Al type 1, -0·49 [-2·16 to 0·86], type 2, -2·45 [-5·47 to 0·27], and type 3, -1·46 [-3·60 to 0·10]; and 1/10 IPV-Al type 1, -1·47 [-3·62 to 0·10], type 2, -3·94 [-7·28 to -0·97], and type 3, -0·49 [-2·17 to 0·86]). Three serious adverse events occurred that were unrelated to the vaccine.INTERPRETATION: The lowest dose (1/10 IPV-Al) of the vaccine performed well both after two and three doses. Based on these results, this new vaccine is under investigation in phase 3 trials.FUNDING: Bill&Melinda Gates Foundation.

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PMID: 

Neurochem Int. 2019 Dec ;131:104580. Epub 2019 Oct 15. PMID: 31626830

Abstract Title: 

Developmental impact of air pollution on brain function.

Abstract: 

Air pollution is an important contributor to the global burden of disease, particularly to respiratory and cardiovascular diseases. In recent years, evidence is accumulating that air pollution may adversely affect the nervous system as shown by human epidemiological studies and by animal models. Age appears to play a relevant role in air pollution-induced neurotoxicity, with growing evidence suggesting that air pollution may contribute to neurodevelopmental and neurodegenerative diseases. Traffic-related air pollution (e.g. diesel exhaust) is an important contributor to urban air pollution, and fine and ultrafine particulate matter (PM) may possibly be its more relevant component. Air pollution is associated with increased oxidative stress and inflammation both in the periphery and in the nervous system, and fine and ultrafine PM can directly access the central nervous system. This short review focuses on the adverse effects of air pollution on the developing brain; it discusses some characteristics that make the developing brain more susceptible to toxic effects, and summarizes the animal and human evidence suggesting that exposure to elevated air pollution is associated with a number of behavioral and biochemical adverse effects. It also discusses more in detail the emerging evidence of an association between perinatal exposure to air pollution and increased risk of autism spectrum disorder. Some of the common mechanisms that may underlie the neurotoxicity and developmental neurotoxicity of air pollution are also discussed. Considering the evidence presented in this review, any policy and legislative effort aimed at reducing air pollution would be protective of children's well-being.

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PMID: 

Clin Infect Dis. 2017 Sep 1 ;65(5):851-854. PMID: 28444156

Abstract Title: 

The Immunogenicity of Fractional Intradermal Doses of the Inactivated Poliovirus Vaccine Is Associated With the Size of the Intradermal Fluid Bleb.

Abstract: 

The immunogenicity of fractional (one-fifth, 0.1 mL) intradermal doses of the inactivated poliovirus vaccine (ID fIPV) is positively correlated with the size of the intradermal fluid bleb. Training of vaccinators for campaign and routine ID fIPV administration should focus on generating an 8- to 10-mm bleb with each injection. Clinical Trials Registration NCT01847872.

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PMID: 

Environ Res. 2020 Jan ;180:108817. Epub 2019 Oct 12. PMID: 31627156

Abstract Title: 

Ambient air pollution and diabetes: A systematic review and meta-analysis.

Abstract: 

BACKGROUND: Air pollutants are suggested to be related to type 2 diabetes (T2D). Since several high quality papers on air pollutants and T2D have been published beyond the last reviews, an extended systematic review is highly warranted. We review epidemiological studies to quantify the association between air pollutants and T2D, and to answer if diabetes patients are more vulnerable to air pollutants.METHODS: We systematically reviewed the databases of PubMed and Web of Science based on the guidelines of the Preferred Reporting Items for Systematic review and Meta-analysis (PRISMA). We calculated odds ratios (OR) or hazard ratios (HR) and their 95% confidence intervals (CI) to assess the strength of the associations between air pollutants [e.g., particulate matter with diameter ≤ 2.5 μm (PM), particulate matter with diameter ≤ 10 μm (PM), and nitrogen dioxide (NO)] and T2D. We evaluated the quality and risk of bias of the included studies and graded the credibility of the pooled evidence using several recommended tools. We also performed sensitivity analysis, meta-regression analysis, and publication bias test.RESULTS: Out of 716 articles identified, 86 were used for this review and meta-analysis. Meta-analyses showed significant associations of PMwith T2D incidence (11 studies; HR = 1.10, 95% CI = 1.04-1.17 per 10 μg/mincrement; I = 74.4%) and prevalence (11 studies; OR = 1.08; 95% CI = 1.04-1.12 per 10 μg/mincrement; I = 84.3%), of PMwith T2D prevalence (6 studies; OR = 1.10; 95% CI = 1.03-1.17 per 10 μg/mincrement; I = 89.5%) and incidence (6 studies; HR = 1.11; 95% CI = 1.00-1.22 per μg/mincrement; I = 70.6%), and of NOwith T2D prevalence (11 studies; OR = 1.07; 95% CI = 1.04-1.11 per 10 μg/mincrement; I = 91.1%). The majority of studies on glucose-homoeostasis markers also showed increased risks with higher air pollutants levels, but the studies were too heterogeneous for meta-analysis. Overall, patients with diabetes might be more vulnerable to PM.CONCLUSIONS: Recent publications strengthened the evidence for adverse effects of ambient air pollutants exposure (especially for PM) on T2D and that diabetic patients might be more vulnerable to air pollutants exposure.

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PMID: 

J Infect Dis. 2019 Oct 8 ;220(10):1551-1557. PMID: 30958543

Abstract Title: 

Immunogenicity and Safety of a Sabin Strain-Based Inactivated Polio Vaccine: A Phase 3 Clinical Trial.

Abstract: 

BACKGROUND: The Sabin strain-based inactivated polio vaccine (sIPV) plays a vital role in eradicating poliomyelitis in developing countries.METHODS: The study was designed as a randomized, controlled, double-blinded, noninferiority trial. A total of 1200 healthy infants aged 60-90 days were enrolled and randomly assigned to receive 3 doses of either sIPV (the experimental arm) or IPV (the control arm) at days 0, 30, and 60. Immunogenicity and safety outcomes were assessed using the per-protocol and safety populations, respectively.RESULTS: A total of 553 and 562 participants in the sIPV and IPV groups, respectively, were included in the per-protocol population. Seroconversion rates in the sIPV and IPV groups were 98.0% and 94.1%, respectively, for type 1 poliovirus (P

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