Herd immunity is not a motivator for vaccination.

PMID: 

Am J Prev Med. 2013 Jul ;45(1):118-121. PMID: 23790997

Abstract Title: 

Conscious consideration of herd immunity in influenza vaccination decisions.

Abstract: 

BACKGROUND: Influenza vaccination decisions may be influenced by perceived risk reduction related to herd immunity.PURPOSE: This paper examines how free-riding (i.e., foregoing vaccination because of reduced risk perceptions related to herd immunity) or protective benefits to the community affect vaccination decisions.METHODS: A survey of a nationally representative panel of U.S. adults (N=442 respondents; data collected and analyzed during 2012) asked about how respondents made vaccination decisions, including whether and how vaccination among the members of respondents' social networks influenced their own vaccination decisions.RESULTS: Most individuals (61%) reported that vaccination in the social network would not influence their decision. Among those perceiving being influenced by vaccination in their social network, most stated that an increase in network vaccination coverage would make them more likely to get vaccinated, rather than less. Overall, only 6% (28 of 442) gave a response consistent with the reduced-risk logic of herd immunity, which was more common among those stating that they would be less likely to get vaccinated (emphasizing free-riding) than among those more likely to get vaccinated (emphasizing social protection; 33% vs 11%, two-sided, p=0.0005). The reduced-risk logic of herd immunity, and more specifically free-riding, is consciously considered by relatively few individuals. Far more common are social influences bolstering personal vaccination, such as peer pressure and social learning (6% vs 11%, two-sided, p=0.015).CONCLUSIONS: Interventionists may be more successful by capitalizing on existing social-influence considerations than by trying to combat the conscious lure of free-riding.

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Undervaccinated children have lower outpatient rates.

PMID: 

JAMA Pediatr. 2013 Mar 1 ;167(3):274-81. PMID: 23338829

Abstract Title: 

A population-based cohort study of undervaccination in 8 managed care organizations across the United States.

Abstract: 

OBJECTIVES To examine patterns and trends of undervaccination in children aged 2 to 24 months and to compare health care utilization rates between undervaccinated and age-appropriately vaccinated children. DESIGN Retrospective matched cohort study. SETTING Eight managed care organizations of the Vaccine Safety Datalink. PARTICIPANTS Children born between 2004 and 2008. MAIN EXPOSURE Immunization records were used to calculate the average number of days undervaccinated. Two matched cohorts were created: 1 with children who were undervaccinated for any reason and 1 with children who were undervaccinated because of parental choice. For both cohorts, undervaccinated children were matched to age-appropriately vaccinated children by birth date, managed care organization, and sex. MAIN OUTCOME MEASURES Rates of undervaccination, specific patterns of undervaccination, and health care utilization rates. RESULTS Of 323 247 children born between 2004 and 2008, 48.7% were undervaccinated for at least 1 day before age 24 months. The prevalence of undervaccination and specific patterns of undervaccination increased over time (P < .001). In a matched cohort analysis, undervaccinated children had lower outpatient visit rates compared with children who were age-appropriately vaccinated (incidence rate ratio [IRR], 0.89; 95% CI, 0.89- 0.90). In contrast, undervaccinated children had increased inpatient admission rates compared with age-appropriately vaccinated children (IRR, 1.21; 95% CI, 1.18-1.23). In a second matched cohort analysis, children who were undervaccinated because of parental choice had lower rates of outpatient visits (IRR, 0.94; 95% CI, 0.93-0.95) and emergency department encounters (IRR, 0.91; 95% CI, 0.88-0.94) than age-appropriately vaccinated children. CONCLUSIONS Undervaccination appears to be an increasing trend. Undervaccinated children appear to have different health care utilization patterns compared with age-appropriately vaccinated children.

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Although vaccines may theoretically “eliminate” some strains of viruses, they may be replaced with other strains unaffected by vaccination.

PMID: 

BMC Public Health. 2012 Oct 16 ;12:878. Epub 2012 Oct 16. PMID: 23072714

Abstract Title: 

Systematic review of studies evaluating the broader economic impact of vaccination in low and middle income countries.

Abstract: 

BACKGROUND: Most health economic evaluations of childhood vaccination only capture the health and short-term economic benefits. Measuring broader, long-term effects of vaccination on productivity and externalities could provide a more complete picture of the value of vaccines.METHOD: MEDLINE, EconLit and NHS-EED databases were searched for articles published between January 1990 and July 2011, which captured broader economic benefits of vaccines in low and middle income countries. Studies were included if they captured at least one of the following categories on broader economic impact: outcome-related productivity gains, behaviour-related productivity gains, ecological externalities, equity gains, financial sustainability gains or macroeconomic benefits.RESULTS: Twenty-six relevant studies were found, including observational studies, economic models and contingent valuation studies. Of the identified broader impacts, outcome-related productivity gains and ecological externalities were most commonly accounted for. No studies captured behaviour-related productivity gains or macroeconomic effects. There was some evidence to show that vaccinated children 8-14 years of age benefit from increased cognitive ability. Productivity loss due to morbidity and mortality was generally measured using the human capital approach. When included, herd immunity effects were functions of coverage rates or based on reduction in disease outcomes. External effects of vaccines were observed in terms of equitable health outcomes and contribution towards synergistic and financially sustainable healthcare programs.CONCLUSION: Despite substantial variation in the methods of measurement and outcomes used, the inclusion of broader economic impact was found to improve the attractiveness of vaccination. Further research is needed on how different tools and techniques can be used in combination to capture the broader impact of vaccination in a way that is consistent with other health economic evaluations. In addition, more country level evidence is needed from low and middle income countries to justify future investments in vaccines and immunization programs. Finally, the proposed broader economic impact framework may contribute towards better communication of the economic arguments surrounding vaccine uptake, leading to investments in immunization by stakeholders outside of the traditional health care sector such as ministries of finance and national treasuries.

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Exposure to perifluorinated compounds are associated with reduced humoral responses to vaccines.

PMID: 

JAMA. 2012 Jan 25 ;307(4):391-7. PMID: 22274686

Abstract Title: 

Serum vaccine antibody concentrations in children exposed to perfluorinated compounds.

Abstract: 

CONTEXT: Perfluorinated compounds (PFCs) have emerged as important food contaminants. They cause immune suppression in a rodent model at serum concentrations similar to those occurring in the US population, but adverse health effects of PFC exposure are poorly understood.OBJECTIVE: To determine whether PFC exposure is associated with antibody response to childhood vaccinations.DESIGN, SETTING, AND PARTICIPANTS: Prospective study of a birth cohort from the National Hospital in the Faroe Islands. A total of 656 consecutive singleton births were recruited during 1997-2000, [corrected] and 587 participated in follow-up through 2008.MAIN OUTCOME MEASURES: Serum antibody concentrations against tetanus and diphtheria toxoids at ages 5 and 7 years.RESULTS: Similar to results of prior studies in the United States, the PFCs with the highest serum concentrations were perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Among PFCs in maternal pregnancy serum, PFOS showed the strongest negative correlations with antibody concentrations at age 5 years, for which a 2-fold greater concentration of exposure was associated with a difference of -39% (95% CI, -55% to -17%) in the diphtheria antibody concentration. PFCs in the child's serum at age 5 years showed uniformly negative associations with antibody levels, especially at age 7 years, except that the tetanus antibody level following PFOS exposure was not statistically significant. In a structural equation model, a 2-fold greater concentration of major PFCs in child serum was associated with a difference of -49% (95% CI, -67% to -23%) in the overall antibody concentration. A 2-fold increase in PFOS and PFOA concentrations at age 5 years was associated with odds ratios between 2.38 (95% CI, 0.89 to 6.35) and 4.20 (95% CI, 1.54 to 11.44) for falling below a clinically protective level of 0.1 IU/mL for tetanus and diphtheria antibodies at age 7 years.CONCLUSION: Elevated exposures to PFCs were associated with reduced humoral immune response to routine childhood immunizations in children aged 5 and 7 years.

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Lack of varicella immunity is common in children and adolescents.

PMID: 

Vaccine. 2011 Oct 13 ;29(44):7835-41. Epub 2011 Aug 2. PMID: 21816197

Abstract Title: 

Presence of immune memory and immunity to hepatitis B virus in adults after neonatal hepatitis B vaccination.

Abstract: 

Neonatal vaccination against hepatitis B virus (HBV) infection was launched in the 1980s in Qidong, China, where HBV and hepatocellular carcinoma were highly prevalent. Presence of immune memory and immunity against HBV in adults needs to be clarified. From a cohort of 806 who received plasma-derived Hep-B-Vax as neonates and were consecutively followed at ages 5, 10, and 20 years, 402 twenty-four-year-old adults were recruited for booster test. Among them 4 (1%) were found to be HBsAg(+), 27 (6.7%) were HBsAg(-)anti-HBc(+), 121 (30.2%) were HBsAg(-)anti-HBc(-)anti-HBs(+), and 252 (62.4%) were HBsAg(-)anti-HBc(-)anti-HBs(-). Of them, 141 subjects with HBsAg(-)anti-HBc(-) were boosted with 10-μg recombinant HBV vaccine on day-0 and 1-month. The conversion rates of anti-HBs ≥ 10 mIU/ml on D10-12 and 1-month post-booster were 71.4% and 87.3% respectively in the vaccinees who were anti-HBs(+) at age 5, higher than in those who were anti-HBs(-) at age 5, 57.5% and 80.0% respectively, butno statistically significant. After the second dose of booster, all subjects with anti-HBs(+) at age 5 had anti-HBs>500 mIU/ml. However, 6/40 subjects, with anti-HBs(-) at age 5, had anti-HBs

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Adults with a previously received seasonal influenza vaccination had a reduced antibody response to the H1N1 vaccine.

PMID: 

Clin Vaccine Immunol. 2011 Sep ;18(9):1401-5. Epub 2011 Jul 27. PMID: 21795459

Abstract Title: 

Immunogenicity, boostability, and sustainability of the immune response after vaccination against Influenza A virus (H1N1) 2009 in a healthy population.

Abstract: 

The emergence of a new influenza A virus (H1N1) variant in 2009 led to a worldwide vaccination program, which was prepared in a relatively short period of time. This study investigated the humoral immunity against this virus before and after vaccination with a 2009 influenza A virus (H1N1) monovalent MF59-adjuvanted vaccine, as well as the persistence of vaccine-induced antibodies. Our prospective longitudinal study included 498 health care workers (mean age, 43 years; median age, 44 years). Most (89%) had never or only occasionally received a seasonal influenza virus vaccine, and 11% were vaccinated annually (on average, for>10 years). Antibody titers were determined by a hemagglutination inhibition (HI) assay at baseline, 3 weeks after the first vaccination, and 5 weeks and 7 months after the second vaccination. Four hundred thirty-five persons received two doses of the 2009 vaccine. After the first dose, 79.5% developed a HI titer of≥40. This percentage increased to 83.3% after the second dose. Persistent antibodies were found in 71.9% of the group that had not received annual vaccinations and in 43.8% of the group that had received annual vaccinations. The latter group tended to have lower HI titers (P=0.09). With increasingage, HI titers decreased significantly, by 2.4% per year. A single dose of the 2009 vaccine was immunogenic in almost 80% of the study population, whereas an additional dose resulted in significantly increased titers only in persons over 50. Finally, a reduced HI antibody response against the 2009vaccine was found in adults who had previously received seasonal influenza virus vaccination. More studies on the effect of yearly seasonal influenza virus vaccination on the immune response are warranted.

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Immunologic hyporesponsiveness to meningococcal vaccine in African toddlers.

PMID: 

Clin Vaccine Immunol. 2011 Sep ;18(9):1492-6. Epub 2011 Jul 13. PMID: 21752951

Abstract Title: 

Meningococcal group C and w135 immunological hyporesponsiveness in african toddlers.

Abstract: 

A phase II clinical study was conducted in African toddlers (aged 12 to 23 months), with subjects receiving either investigational meningococcal group A conjugate (PsA-TT), meningococcal ACWY polysaccharide (PsACWY), or Haemophilus influenzae type b (Hib-TT) vaccine. Ten months following vaccination, the 3 study groups were further randomized to receive a dose of PsA-TT, a 1/5 dose of PsACWY, or a dose of Hib-TT vaccine. Group A serum bactericidal antibody (SBA) results have been reported previously, with PsA-TT demonstrating superior immunogenicity versus PsACWY vaccine. Immunogenicity for serogroups W135 and C was assessed by SBA assay to investigate the impact of multiple doses in this age group. Blood samples were taken prior to vaccination, 28 days and 40 weeks post-primary vaccination, and 7 and 28 days post-booster vaccination with a 1/5 dose of PsACWY. Subjects who had previously received a full dose of PsACWY had W135 SBA geometric mean titers (GMTs) of 26.1 and 4.4 at 7 and 28 days post-booster vaccination with a 1/5 PsACWY dose, respectively, whereas the W135 SBA GMTs of naïve subjects at these time points following vaccination with a 1/5 dose of PsACWY were 861.1 and 14.6, respectively. Similar differences were observed for serogroup C, with SBA GMTs of 99 and 5.9 at 7 and 28 days post-booster vaccination with a 1/5 dose of PsACWY, respectively, for naïve subjects,compared to 4.1 and 3.2 for previously vaccinated subjects. Immunologic hyporesponsiveness for groups C and W135 was observed following a full dose of PsACWY vaccine at 12 to 23 months of age and a 1/5 dose of PsACWY 10 months later compared to the case for PsACWY-naïve subjects receiving a 1/5 dose of PsACWY vaccine.

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Mangifera indica leaf extract was effective in maintaining a long-term hypoglycemic effect and significantly increased insulin sensitivity.

PMID: 

PLoS One. 2020 ;15(1):e0227105. Epub 2020 Jan 8. PMID: 31914140

Abstract Title: 

Aqueous extract from Mangifera indica Linn. (Anacardiaceae) leaves exerts long-term hypoglycemic effect, increases insulin sensitivity and plasma insulin levels on diabetic Wistar rats.

Abstract: 

BACKGROUND: Diabetes mellitus is one of the most common todays public health problems. According to a survey by the World Health Organization, this metabolic disorder has reached global epidemic proportions, with a worldwide prevalence of 8.5% in the adult population.OBJECTIVES: The present study aimed to investigate the hypoglycemic effect of aqueous extract of Mangifera indica (EAMI) leaves in streptozotocin-induced diabetic rats.METHODS: Sixty male rats were divided into 2 groups: Normoglycemic and Diabetic. Each group was subdivided into negative control, glibenclamide 3 or 10 mg/kg, EAMI 125, 250, 500, and 1000 mg/kg. Intraperitoneal injection of streptozotocin 100 mg/kg was used to DM induction. The hypoglycemic response was assessed acutely after two and four weeks of treatment. After a 6-hour fasting period, the fasting blood glucose of animals was verified, and 2.5 g/kg glucose solution was orally administered. The insulin tolerance test and plasma insulin levels assessment were performed in the morning after fasting of 12 to 14 hours.RESULTS AND CONCLUSION: The chemical analysis of EAMI showed high levels of phenolic compounds. There was no significant difference in fasting blood glucose between normoglycemic and diabetic groups, and that EAMI did not have an acute effect on diabetes. After two and four weeks of treatment, the extract significantly reduced blood glucose levels, exceeding glibenclamide effects. EAMI was effective in maintaining the long-term hypoglycemic effect, as well as, significantly increased the sensitivity of diabetic animals to insulin and the plasma insulin level.

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These results suggested that mangiferin serves as a potentially applicable candidate for treating osteoarthritis.

PMID: 

Oxid Med Cell Longev. 2019 ;2019:8783197. Epub 2019 Oct 15. PMID: 31885823

Abstract Title: 

Mangiferin Prevents TBHP-Induced Apoptosis and ECM Degradation in Mouse Osteoarthritic Chondrocytes via Restoring Autophagy and Ameliorates Murine Osteoarthritis.

Abstract: 

Osteoarthritis (OA) is an age-related degenerative disease with complicated pathology involving chondrocyte apoptosis and extracellular matrix (ECM) degradation. Previous studies have shown that moderate autophagy has a protective effect against apoptosis in chondrocyte. Mangiferin is a natural polyphenol and exerts multiple pharmacological effects on different diseases in various preclinical studies. In this study, we investigated the effects of mangiferin on OA and delineated a potential molecular mechanism. In vitro, mangiferin treatment inhibited the expression of proapoptotic proteins induced by-butyl hydroperoxide (TBHP), increased the expression of antiapoptotic Bcl-2, and prevented ECM degradation by inhibiting the production of matrix-degrading enzyme. Mechanistically, mangiferin enhanced autophagy by activating the AMP-activated protein kinase (AMPK) signaling pathway. On the contrary, inhibition of autophagy partly abolished the protective effects of mangiferin on antiapoptosis and ECM synthesis in TBHP-treated chondrocyte. Correspondingly, the protective effect of mangiferin was also found in a mouse OA model. In conclusion, our results suggested that mangiferin serves as a potentially applicable candidate for treating OA.

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Mangiferin suppresses human metastatic osteosarcoma cell growth.

PMID: 

AMB Express. 2020 Jan 18 ;10(1):13. Epub 2020 Jan 18. PMID: 31955303

Abstract Title: 

Mangiferin suppresses human metastatic osteosarcoma cell growth by down-regulating the expression of metalloproteinases-1/2 and parathyroid hormone receptor 1.

Abstract: 

The study evaluates the protective effect of mangiferin on osteosarcoma cell proliferation and metastasis. Saos-2 and U2OS cells were treated with mangiferin (25, 50, 75 and 100 µM) for 72 h. Mangiferin reduced the cell viability, invasion, and cell adhesion and migration rate. Matrix metalloproteinases-2/9 (MMP-2/9) mRNA expression was reduced significantly, while the levels of tissue inhibitors of metalloproteinases-1/2 (TIMP-1/2) were elevated in Saos-2 and U2OS cells. Mangiferin treatment significantly reduced parathyroid hormone receptor 1 (PTHR1) mRNA and protein expression by more than 0.5-fold in both osteosarcoma cells. In addition, the immunofluorescent analysis also showed decreased PTHR1 expression following treatment with mangiferin. In summary, we have demonstrated that treatment with mangiferin reduces cell viability, proliferation, invasion, adhesion and migration, and induces apoptosis of osteosarcoma cells. Therefore, treatment with mangiferin can be effective agent in inhibiting growth and inducing apoptosis in osteosarcoma cells. Our experimental results provide evidence for the therapeutic effect of mangiferin in osteosarcoma cells.

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