PMID: 

Vaccine. 2014 Oct 7 ;32(44):5809-15. Epub 2014 Aug 27. PMID: 25173482

Abstract Title: 

Investigations into an outbreak of suppurative lymphadenitis with BCG vaccine SSI(®) in Singapore.

Abstract: 

INTRODUCTION: From 2011 to 2012, we received an unexpectedly high number of reports of suppurative lymphadenitis following administration of a BCG vaccine used in our childhood vaccination programme in Singapore. We sought to determine the local incidence rates of BCG-associated suppurative lymphadenitis across the 2009 to 2012 vaccinated cohorts, and to analyse the potential factors contributing to this outbreak.METHODS: Reports of lymphadenitis following BCG vaccination from an AEFI active surveillance system at the KK Women's and Children's Hospital (KKH) and passive surveillance data from other healthcare institutions were reviewed. All valid reports received from January 2009 to December 2013 involving neonates vaccinated with the BCG vaccine in 2009 to 2012 that met case definitions were included in our analysis. Details of the demographics and vaccination history of the child, and statistics from the local vaccination programme were also obtained. Potential contributory factors were selected for further investigation based on a literature review of similar outbreaks overseas.RESULTS: We identified 283 cases of lymphadenitis, of which 76% were suppurative. A spike in suppurative lymphadenitis cases was seen in the 2011 vaccinated cohort, with an incidence rate of 3.16 per 1000 vaccinees, as compared to 0.71 to 0.85 per 1000 in the 2009, 2010 and 2012 cohorts. Our investigations identified the likely cause of the outbreak to be batch-related, arising from manufacturing issues encountered by the manufacturer, after ruling out vaccine administration-related and host-related factors.CONCLUSIONS: The three-fold spike in BCG-associated suppurative lymphadenitis cases observed in the 2011 vaccinated cohort, possibly due to batch-to-batch variation of the vaccine, highlights that manufacturing controls can continue to be a challenge. Development of a more sensitive assay to test the reactogenicity of the BCG vaccine may help reduce the occurrence of such outbreaks and improve public confidence in the nation's vaccination programme.

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PMID: 

Nutr Res. 2019 Nov 16 ;73:27-37. Epub 2019 Nov 16. PMID: 31841745

Abstract Title: 

Pomegranate peel extract reduced colonic damage and bacterial translocation in a mouse model of infectious colitis induced by Citrobacter rodentium.

Abstract: 

The pomegranate fruit peel is a rich source of polyphenols including punicalins, punicalagins, and ellagic acids, but is considered an agricultural waste product. Pomegranate derived products have been reported to have a wide variety of health promoting benefits including antibacterial properties in vitro but there is limited evidence of their antibacterial properties in vivo. The purpose of this study was to test the in vivo antibacterial properties of a pomegranate peel extract (PPX) containing punicalin, punicalagin, and ellagic acid. C3H/He mice were orally pre-treated with water or PPX prior to infection with the mouse bacterial pathogen, Citrobacter rodentium (Cr) that mimics many aspects of human enteropathogenic Escherichia coli infections. Fecal excretion of Cr was monitored and mice were euthanized on day 12 post-infection to assess Cr colonization of the colon and spleen, histological changes, and gene expression. PPX-treatment reduced Cr infection induced weight loss and mortality that was observed in water-treated infected mice. However, Cr colonization of the colon and clearance was unaffected by PPX-treatment. Consistent with this, PPX treatment did not alter the potent Th1/Th17 pro-inflammatory response elicited by Cr infection. Significant colonization of the spleen was only seen in water-treated infected mice and was inversely correlated with the dose of PPX administered. PPX treatment decreased the extent of Cr-induced colon damage that correlated with decreased mortality and reduced colonization of the spleen. Thus, a pomegranate peel extract contains bioactive compounds that mitigate the deleterious effects of an in vivo infection with the model enteropathogenic bacteria, Cr.

PMID: 

Vaccine. 2017 03 14 ;35(12):1652-1661. Epub 2017 Feb 17. PMID: 28216183

Abstract Title: 

Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials.

Abstract: 

BACKGROUND: Novel vaccine strategies are required to provide protective immunity in tuberculosis (TB) and prevent development of active disease. We investigated the safety and immunogenicity of a novel TB vaccine candidate, H4:IC31 (AERAS-404) that is composed of a fusion protein of M. tuberculosis antigens Ag85B and TB10.4 combined with an IC31® adjuvant.METHODS: BCG-vaccinated healthy subjects were immunized with various antigen (5, 15, 50, 150μg) and adjuvant (0, 100, 500nmol) doses of the H4:IC31 vaccine (n=106) or placebo (n=18) in two randomized, double-blind, placebo-controlled phase I studies conducted in a low TB endemic setting in Sweden and Finland. The subjects were followed for adverse events and CD4T cell responses.RESULTS: H4:IC31 vaccination was well tolerated with a safety profile consisting of mostly mild to moderate self-limited injection site pain, myalgia, arthralgia, fever and post-vaccination inflammatory reaction at the screening tuberculin skin test injection site. The H4:IC31 vaccine elicited antigen-specific CD4T cell proliferation and cytokine production that persisted 18weeks after the last vaccination. CD4T cell expansion, IFN-γ production and multifunctional CD4Th1 responses were most prominent after two doses of H4:IC31 containing 5, 15, or 50μg of H4 in combination with the 500nmol IC31 adjuvant dose.CONCLUSIONS: The novel TB vaccine candidate, H4:IC31, demonstrated an acceptable safety profile and was immunogenic, capable of triggering multifunctional CD4T cell responses in previously BCG-vaccinated healthy individuals. These dose-escalation trials provided evidence that the optimal antigen-adjuvant dose combinations are 5, 15, or 50μg of H4 and 500nmol of IC31.TRIAL REGISTRATION: ClinicalTrials.gov, NCT02066428 and NCT02074956.

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PMID: 

J Med Internet Res. 2020 Jan 3 ;22(1):e15684. Epub 2020 Jan 3. PMID: 31899452

Abstract Title: 

Health Effects Associated With Electronic Cigarette Use: Automated Mining of Online Forums.

Abstract: 

BACKGROUND: Our previous infodemiological study was performed by manually mining health-effect data associated with electronic cigarettes (ECs) from online forums. Manual mining is time consuming and limits the number of posts that can be retrieved.OBJECTIVE: Our goal in this study was to automatically extract and analyze a large number (>41,000) of online forum posts related to the health effects associated with EC use between 2008 and 2015.METHODS: Data were annotated with medical concepts from the Unified Medical Language System using a modified version of the MetaMap tool. Of over 1.4 million posts, 41,216 were used to analyze symptoms (undiagnosed conditions) and disorders (physician-diagnosed terminology) associated with EC use. For each post, sentiment (positive, negative, and neutral) was also assigned.RESULTS: Symptom and disorder data were categorized into 12 organ systems or anatomical regions. Most posts on symptoms and disorders contained negative sentiment, and affected systems were similar across all years. Health effects were reported most often in the neurological, mouth and throat, and respiratory systems. The most frequently reported symptoms and disorders were headache (n=939), coughing (n=852), malaise (n=468), asthma (n=916), dehydration (n=803), and pharyngitis (n=565). In addition, users often reported linked symptoms (eg, coughing and headache).CONCLUSIONS: Online forums are a valuable repository of data that can be used to identify positive and negative health effects associated with EC use. By automating extraction of online information, we obtained more data than in our prior study, identified new symptoms and disorders associated with EC use, determined which systems are most frequently adversely affected, identified specific symptoms and disorders most commonly reported, and tracked health effects over 7 years.

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PMID: 

Vaccine. 2017 04 11 ;35(16):2084-2091. Epub 2017 Mar 15. PMID: 28318766

Abstract Title: 

Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial.

Abstract: 

INTRODUCTION: BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants.METHODS: Within 7days after birth, children were randomised 1:1 to BCG vaccination or to the control group (no intervention). After three routine vaccinations given at age 3, 5 and 12months, antibodies against DiTeKiPol/Act-Hib and Prevenar 13 (Streptococcus pneumoniae serotype type 4, 6B, 9V, 14, 18C, 19F and 23F) were measured 4weeks after the third vaccine dose.RESULTS: Among the 300 included children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by 'age at randomisation' we found a possible inducing effect of BCG on antibodies against B. pertussis and all pneumococcal serotypes, when BCG was given after the first day of life. Girls had significantly higher antibody levels for Haemophilus influenza type b and pneumococcus than boys.CONCLUSIONS AND RELEVANCE: Three routine vaccinations with DiTeKiPol/Act-Hib and Prevenar 13 induced sero-protective levels in almost all children. No overall effect of neonatal BCG vaccination was observed.

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PMID: 

Vaccine. 2013 Feb 27 ;31(10):1447-52. Epub 2012 Nov 8. PMID: 23142308

Abstract Title: 

U.S. Postlicensure safety surveillance for adolescent and adult tetanus, diphtheria and acellular pertussis vaccines: 2005-2007.

Abstract: 

BACKGROUND: Pre-licensure clinical trials for two U.S. licensed tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines did not reveal any major safety concerns. However, routine use in large adolescent and adult populations could reveal rare and potentially serious adverse events (AEs).METHODS: To characterize reported AEs following Tdap vaccination and identify potential safety concerns warranting further evaluation, we analyzed data from the Vaccine Adverse Event Reporting System (VAERS) and assessed the frequency and proportions of AEs and reporting rates (reports per 100,000 vaccine doses distributed).RESULTS: A total of 2090 reports (7% were serious; 55% listed Tdap alone) involving Tdap vaccines were submitted to VAERS May 2005-June 2007. The crude reporting rate was 10.2 per 100,000 vaccine doses distributed. The median age of vaccinees was 22 years, and the female to male ratio was about 2 to 1. The majority of reports described common local and systemic signs and symptoms, such as injection site reactions, fever, and headache. Rarely reported AEs included myopericarditis, demyelinating diseases of the central nervous system, Guillain-Barré Syndrome, syncope, encephalopathy/encephalitis, seizure, Bell's palsy, anaphylaxis, and thrombocytopenia.CONCLUSIONS: Because adolescents and adults were not routinely vaccinated against pertussis in the past, this surveillance summary provides important – and reassuring – information about the use of Tdap in these age groups. Although subject to the limitations of passive surveillance, the findings of this VAERS review support the pre-licensure clinical trial data with regard to the safety of the U.S. licensed Tdap vaccines. Continued monitoring of clinically significant AEs that are temporally associated with Tdap vaccination and further assessment of such events using controlled observational studies may provide additional information about the safety of these vaccines.

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PMID: 

Am J Prev Med. 2019 Dec 28. Epub 2019 Dec 28. PMID: 31902685

Abstract Title: 

Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017.

Abstract: 

INTRODUCTION: The association between e-cigarette use and chronic bronchitis, emphysema, and chronic obstructive pulmonary disease has not been studied thoroughly, particularly in populations defined by concomitant combustible smoking status.METHODS: Using pooled 2016 and 2017 data from the Behavioral Risk Factor Surveillance System, investigators studied 705,159 participants with complete self-reported information on e-cigarette use, combustible cigarette use, key covariates, and chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. Current e-cigarette use was the main exposure, with current use further classified as daily or occasional use. The main outcome was defined as reported ever having a diagnosis of chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. For all the analyses, multivariable adjusted logistic regression was used, with the study population stratified by combustible cigarette use status (never, former, or current). All the analyses were conducted in 2019.RESULTS: Of 705,159 participants, 25,175 (3.6%) were current e-cigarette users, 64,792 (9.2%) current combustible cigarette smokers, 207,905 (29.5%) former combustible cigarette smokers, 432,462 (61.3%) never combustible cigarette smokers, and 14,036 (2.0%) dual users of e-cigarettes and combustible cigarettes. A total of 53,702 (7.6%) participants self-reported chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. Among never combustible cigarette smokers, current e-cigarette use was associated with 75% higher odds of chronic bronchitis, emphysema, or chronic obstructive pulmonary disease compared with never e-cigarette users (OR=1.75, 95% CI=1.25, 2.45), with daily users of e-cigarettes having the highest odds (OR=2.64, 95% CI=1.43, 4.89). Similar associations between e-cigarette use and chronic bronchitis, emphysema, or chronic obstructive pulmonary disease were noted among both former and current combustible cigarette smokers.CONCLUSIONS: The results suggest possible e-cigarette-related pulmonary toxicity across all the categories of combustible cigarette smoking status, including those who had never smoked combustible cigarettes.

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PMID: 

Eur J Intern Med. 2014 Jul ;25(6):528-32. Epub 2014 May 9. PMID: 24814432

Abstract Title: 

Low seroprevalence of diphtheria, tetanus and pertussis in ambulatory adult patients: the need for lifelong vaccination.

Abstract: 

BACKGROUND: Tetanus, diphtheria, pertussis and measles are vaccine preventable diseases that have been reported to cause morbidity and mortality in adult population in the recent years. We aimed to document the seropositivity rates and vaccination indication for these four vaccine preventable diseases among adult and elderly patients who were seen as outpatients in a university hospital.METHODS: Blood samples for tetanus, diphtheria, pertussis and measles antibodies were obtained. Results were evaluated with regards to protection levels and booster vaccine indications according to the cut-off values.RESULTS: A total of 1367 patients consented for the study and 1303 blood samples were available for analysis at the end of the study. The antibody levels against measles conferred protection in 98% of patients. However, 65% of the patients had no protection for diphtheria, 69% had no protection for tetanus and 90% of the patients had no protection for pertussis. Only 1.3% of the study population had seropositivity against three of the diseases-Tdap booster was indicated in 98.7%. Multivariable logistic regression showed that tetanus protection decreased with increasing age. Having a chronic disease was associated with a lower rate of protective antibodies for pertussis.CONCLUSIONS: We demonstrated very low rates of protection against three of the vaccine preventable diseases of childhood-diphtheria, pertussis and tetanus. Booster vaccinations are required in adult life in accordance with national and international adult vaccination guidelines. The concept of"lifelong vaccination"should be implemented and every encounter with the patient should be regarded as a chance for catch-up.

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PMID: 

Pediatrics. 2015 Jun ;135(6):981-9. Epub 2015 May 4. PMID: 25941309

Abstract Title: 

Tdap vaccine effectiveness in adolescents during the 2012 Washington State pertussis epidemic.

Abstract: 

BACKGROUND: Acellular pertussis vaccines replaced whole-cell vaccines for the 5-dose childhood vaccination series in 1997. A sixth dose of pertussis-containing vaccine, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap), was recommended in 2005 for adolescents and adults. Studies examining Tdap vaccine effectiveness (VE) among adolescents who have received all acellular vaccines are limited.METHODS: To assess Tdap VE and duration of protection, we conducted a matched case-control study during the 2012 pertussis epidemic in Washington among adolescents born during 1993-2000. All pertussis cases reported from January 1 through June 30, 2012, in 7 counties were included; 3 controls were matched by primary provider clinic and birth year to each case. Vaccination histories were obtained through medical records, the state immunization registry, and parent interviews. Participants were classified by type of pertussis vaccine received on the basis of birth year: a mix of whole-cell and acellular vaccines (1993-1997) or all acellular vaccines (1998-2000). We used conditional logistic regression to calculate odds ratios comparing Tdap receipt between cases and controls.RESULTS: Among adolescents who received all acellular vaccines (450 cases, 1246 controls), overall Tdap VE was 63.9% (95% confidence interval [CI]: 50% to 74%). VE within 1 year of vaccination was 73% (95% CI: 60% to 82%). At 2 to 4 years postvaccination, VE declined to 34% (95% CI: -0.03% to 58%).CONCLUSIONS: Tdap protection wanes within 2 to 4 years. Lack of long-term protection after vaccination is likely contributing to increases in pertussis among adolescents.

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PMID: 

JAMA. 2016 Nov 1 ;316(17):1823-1825. PMID: 27802536

Abstract Title: 

Tdap Vaccination During Pregnancy and Microcephaly and Other Structural Birth Defects in Offspring.

Abstract: 

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