PMID: 

Am J Public Health. 2012 Sep ;102(9):e13-4. Epub 2012 Jul 19. PMID: 22813421

Abstract Title: 

Who profits from uncritical acceptance of biased estimates of vaccine efficacy and safety?

Abstract: 

[n/a]

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PMID: 

Vaccine. 2010 Dec 10 ;29(1):11-6. Epub 2010 Oct 27. PMID: 21034823

Abstract Title: 

Imperfect vaccine-induced immunity and whooping cough transmission to infants.

Abstract: 

Whooping cough, caused by B. pertussis and B. parapertussis, has increased in incidence throughout much of the developed world since the 1980s despite high vaccine coverage, causing an increased risk of infection in infants who have substantial disease-induced mortality. Duration of immunity and epidemically significant routes of transmission across age groups remain unclear and deserve further investigation to inform vaccination strategies to better control pertussis burden. The authors analyze age- and species-specific whooping cough tests and vaccine histories in Massachusetts from 1990 to 2008. On average, the disease-free duration is 10.5 years. However, it has been decreasing over time, possibly due to a rising force of infection through increased circulation. Despite the importance of teenage cases during epidemics, wavelet analyses suggest that they are not the most important source of transmission to infants. In addition, the data indicate that the B. pertussis vaccine is not protective against disease induced by B. parapertussis.

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PMID: 

J Infect Dis. 2014 Sep 15 ;210(6):942-53. Epub 2014 Jun 5. PMID: 24903664

Abstract Title: 

Estimating the effectiveness of tetanus-diphtheria-acellular pertussis vaccine (Tdap) for preventing pertussis: evidence of rapidly waning immunity and difference in effectiveness by Tdap brand.

Abstract: 

BACKGROUND: We estimated the vaccine effectiveness (VE) of tetanus-diphtheria-acellular pertussis vaccine (Tdap) for preventing pertussis among adolescents during a statewide outbreak of pertussis in Wisconsin during 2012.METHODS: We used the population-based Wisconsin Immunization Registry (WIR) to construct a cohort of Wisconsin residents born during 1998-2000 and collect Tdap vaccination histories. Reports of laboratory-confirmed pertussis with onset during 2012 were matched to WIR clients. Incidence rate ratios (IRRs) of pertussis and Tdap VE estimates [(1 – IRR)*100%], by year of Tdap vaccine receipt and brand (Boostrix/Adacel), were estimated using Poisson regression.RESULTS: Tdap VE decreased with increasing time since receipt, with VEs of 75.3% (95% confidence interval [CI], 55.2%-86.5%) for receipt during 2012, 68.2% (95% CI, 60.9%-74.1%) for receipt during 2011, 34.5% (95% CI, 19.9%-46.4%) for receipt during 2010, and 11.9% (95% CI, -11.1% to 30.1%) for receipt during 2009/2008; point estimates were higher among Boostrix recipients than among Adacel recipients. Among Tdap recipients, increasing time since receipt was associated with increased risk, and receipt of Boostrix (vs Adacel) was associated with decreased risk of pertussis (adjusted IRR, 0.62 [95% CI, .52-.74]).CONCLUSIONS: Our results demonstrate waning immunity following vaccination with either Tdap brand. Boostrix was more effective than Adacel in preventing pertussis in our cohort, but these findings may not be generalizable to adolescent cohorts that received different diphtheria-tetanus-acellular pertussis vaccines (DTaP) during childhood and should be further examined in studies that include childhood DTaP history.

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PMID: 

Pediatrics. 2016 Mar ;137(3):e20153326. Epub 2016 Feb 5. PMID: 26908667

Abstract Title: 

Waning Tdap Effectiveness in Adolescents.

Abstract: 

BACKGROUND AND OBJECTIVE: Because the effectiveness of diphtheria-tetanus-acellular pertussis (DTaP) vaccine wanes substantially after the fifth dose at ages 4 to 6 years, there is a growing cohort of adolescents who rely on tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) for protection against pertussis. Yet despite high Tdap vaccine coverage among adolescents, California experienced large pertussis outbreaks in 2010 and 2014. We investigated Tdap vaccine effectiveness (VE) and waning within Kaiser Permanente Northern California among adolescents exclusively vaccinated with DTaP vaccines.METHODS: We modeled pertussis risk in relation to Tdap vaccination status among adolescents beginning on their 10th birthday. We estimated the hazard ratio (HR) for each subsequent year after Tdap compared with unvaccinated adolescents by using Cox regression, adjusting for calendar time, age, gender, race, and facility. We calculated VE as 1 – HR. We also treated time since Tdap vaccination as a continuous variable and estimated the change in the HR per 1-year increase since vaccination.RESULTS: On the basis of 1207 pertussis cases, Tdap VE during the first year after vaccination was 68.8% (95% confidence interval [CI] 59.7% to 75.9%), decreasing to 8.9% (95% CI -30.6% to 36.4%) by≥4 years after vaccination. Adolescents who were more remote from Tdap were significantly more likely to test positive for pertussis than were those vaccinated more recently (HR per year 1.35, 95% CI 1.22 to 1.50).CONCLUSIONS: Routine Tdap did not prevent pertussis outbreaks. Among adolescents who have only received DTaP vaccines in childhood, Tdap provided moderate protection against pertussis during the first year and then waned rapidly so that litle protection remained 2-3 years after vaccination..

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PMID: 

Pathophysiology. 2019 Jul 29. Epub 2019 Jul 29. PMID: 31383388

Abstract Title: 

Aqueous garlic extract supresses experimental gentamicin induced renal pathophysiology mediated by oxidative stress, inflammation and Kim-1.

Abstract: 

BACKGROUND: Gentamicin (Gent) has rapid&high bactericidal action in addition to its cheap price. Nevertheless, 30% of gentamicin-treated patients develop nephrotoxicity.OBJECTIVE: To explore the probable nephroprotective effects of the aqueous garlic extract (AGE)&to elucidate its underlying mechanisms via monitoring proinflammatory cytokines as tumer necrosis factor (TNF-α), interleukin 6 (IL-6) and interferon-γ (INF-γ), oxidative stess markers as malondialdehyde (MDA)&superoxide dismutase (SOD)&kidney injury molecule (Kim-1) as a promising early specific biomarker of renal dysfunction.METHODS: 32 adult male rats were divided into 4 equal groups treated for 21 days as: normal control group received normal saline orally, AGE-treated group received AGE at 250 mg/kg/day orally, Gent-treated group received Gent-sulphate intraperitoneal injection at 80 mg/kg /day, and AGE&Gent cotreated group received AGE and Gent concomitantly in the same previous doses. Serum urea, creatinine, glomerular filteration rate (GFR), systolic (SBP) and diastolic blood pressure (DBP), TNF-α, IL-6, INF-γ, MDA and SOD and Kim-1 mRNA expression were evaluated in kidney tissue homogenate. Renal cortex sections stained with Haematoxylin&eosin (H&E) were examined.RESULTS: AGE is nephroprotective through significantly reducing serum urea, creatinine, SBP and DBP, TNF-α, IL-6, INF-γ and MDA (the main product of lipid peroxidation), decreasing expression of Kim-1 mRNA in renal tissue and increasing level of GFR, the natural antioxidant SOD and improving renal histological features of Gent-treated rats.CONCLUSION: AGE normalizes Gent-induced renal dysfunction. Their co-administration is a plausible advice, although the therapeutic efficiency of Gent was not investigated.

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PMID: 

Science. 2012 Apr 27 ;336(6080):489-93. Epub 2012 Mar 22. PMID: 22442383

Abstract Title: 

Microbial exposure during early life has persistent effects on natural killer T cell function.

Abstract: 

Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma as compared with that of specific pathogen-free mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal-but not adult-GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.

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PMID: 

Cancer Causes Control. 2010 Aug ;21(8):1193-201. Epub 2010 Jun 18. PMID: 20559706

Abstract Title: 

Mumps and ovarian cancer: modern interpretation of an historic association.

Abstract: 

BACKGROUND: Epidemiologic studies found childhood mumps might protect against ovarian cancer. To explain this association, we investigated whether mumps might engender immunity to ovarian cancer through antibodies against the cancer-associated antigen MUC1 abnormally expressed in the inflamed parotid gland.METHODS: Through various health agencies, we obtained sera from 161 cases with mumps parotitis. Sera were obtained from 194 healthy controls. We used an ELISA to measure anti-MUC1 antibodies and electro-chemiluminescence assays to measure MUC1 and CA 125. Log-transformed measurements were analyzed by t-tests, generalized linear models, and Pearson or Spearman correlations. We also conducted a meta-analysis of all published studies regarding mumps and ovarian cancer.RESULTS: Adjusting for assay batch, age, and sex, the level of anti-MUC1 antibodies was significantly higher in mumps cases compared to controls (p = 0.002). Free circulating levels of CA 125, but not MUC1, were also higher in cases (p = 0.02). From the meta-analysis, the pooled odds ratio estimate (and 95% CI) for the mumps and ovarian cancer association was 0.81 (0.68-0.96) (p = 0.01).CONCLUSION: Mumps parotitis may lead to expression and immune recognition of a tumor-associated form of MUC1 and create effective immune surveillance of ovarian cancer cells that express this form of MUC1.

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PMID: 

Atherosclerosis. 2015 Aug ;241(2):682-6. Epub 2015 Jun 18. PMID: 26122188

Abstract Title: 

Association of measles and mumps with cardiovascular disease: The Japan Collaborative Cohort (JACC) study.

Abstract: 

OBJECTIVE: Although it has been suggested that exposure to infections during childhood could decrease risk of atherosclerotic cardiovascular disease (CVD), the evidence is scarce. We investigated the association of measles and mumps with CVD.METHODS: 43,689 men and 60,147 women aged 40-79 years at baseline (1988-1990) completed a lifestyle questionnaire, including their history of measles and mumps, and were followed until 2009. Histories of infections were categorized as having no infection (reference), measles only, mumps only, or both infections. Hazard ratios (HR) for mortality from CVD across histories of infections were calculated.RESULTS: Men with measles only had multivariable HR (95% confidence interval) of 0.92 (0.85-0.99) for total CVD, those with mumps only had 0.52 (0.28-0.94) for total stroke and 0.21 (0.05-0.86) for hemorrhagic stroke, and those with both infections had 0.80 (0.71-0.90) for total CVD, 0.71 (0.53-0.93) for myocardial infarction, and 0.83 (0.69-0.98) for total stroke. Women with both infections had 0.83 (0.74-0.92) for total CVD and 0.84 (0.71-0.99) for total stroke. We also compared subjects with measles only or mumps only (reference) and those with both infections. Men with both infections had 0.88 (0.78-0.99) for total CVD. Women with both infections had 0.85 (0.76-0.94) for total CVD, 0.79 (0.67-0.93) for total stroke, 0.78 (0.62-0.98) for ischemic stroke and 0.78 (0.62-0.98) for hemorrhagic stroke.CONCLUSIONS: Measles and mumps, especially in case of both infections, were associated with lower risks of mortality from atherosclerotic CVD.

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PMID: 

J Infect Dis. 2013 Mar 15 ;207(6):990-8. Epub 2012 Dec 21. PMID: 23264672

Abstract Title: 

Largest measles epidemic in North America in a decade–Quebec, Canada, 2011: contribution of susceptibility, serendipity, and superspreading events.

Abstract: 

BACKGROUND: The largest measles epidemic in North America in the last decade, occurred in 2011 in Quebec, Canada, where rates of 1- and 2-dose vaccine coverage among children 3 years of age were 95%-97% and 90%, respectively, with 3%-5% unvaccinated.METHODS: Case patients identified through passive surveillance and outbreak investigation were contacted to determine clinical course, vaccination status, and possible source of infection.RESULTS: There were 21 measles importations and 725 cases. A superspreading event triggered by 1 importation resulted in sustained transmission and 678 cases. The overall incidence was 9.1 per 100,000; the highest incidence was in adolescents 12-17 years old (75.6 per 100,000), who comprised 56% of case patients. Among adolescents, 22% had received 2 vaccine doses. Outbreak investigation showed this proportion to have been an underestimate; active case finding identified 130% more cases among 2-dose recipients. Two-dose recipients had milder illness and a significantly lower risk of hospitalization than those who were unvaccinated or single-dose recipients.CONCLUSIONS: A chance superspreading event revealed an overall level of immunity barely above the elimination threshold when unexpected vulnerability in 2-dose recipients was taken into account. Unvaccinated individuals remain the immunization priority, but a better understanding of susceptibility in 2-dose recipients is needed to define effective interventions if elimination is to be achieved.

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PMID: 

Arch Intern Med. 1994 Aug 22 ;154(16):1815-20. PMID: 8053748

Abstract Title: 

Failure to reach the goal of measles elimination. Apparent paradox of measles infections in immunized persons.

Abstract: 

BACKGROUND: Measles is the most transmissible disease known to man. During the 1980s, the number of measles cases in the United States rose dramatically. Surprisingly, 20% to 40% of these cases occurred in persons who had been appropriately immunized against measles. In response, the United States adopted a two-dose universal measles immunization program. We critically examine the effect of vaccine failure in measles occurring in immunized persons.METHODS: We performed a computerized bibliographic literature search (National Library of Medicine) for all English-language articles dealing with measles outbreaks. We limited our search to reports of US and Canadian school-based outbreaks of measles, and we spoke with experts to get estimates of vaccine failure rates. In addition, we devised a hypothetical model of a school where measles immunization rates could be varied, vaccine failure rates could be calculated, and the percentage of measles cases occurring in immunized students could be determined.RESULTS: We found 18 reports of measles outbreaks in very highly immunized school populations where 71% to 99.8% of students were immunized against measles. Despite these high rates of immunization, 30% to 100% (mean, 77%) of all measles cases in these outbreaks occurred in previously immunized students. In our hypothetical school model, after more than 95% of schoolchildren are immunized against measles, the majority of measles cases occur in appropriately immunized children.CONCLUSIONS: The apparent paradox is that as measles immunization rates rise to high levels in a population, measles becomes a disease of immunized persons. Because of the failure rate of the vaccine and the unique transmissibility of the measles virus, the currently available measles vaccine, used in a single-dose strategy, is unlikely to completely eliminate measles. The long-term success of a two-dose strategy to eliminate measles remains to be determined.

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