Vaccination to prevent varicella: Goldman and King's response to Myers' interpretation of Varicella Active Surveillance Project data.

BACKGROUND: There is increasing evidence that herpes zoster (HZ) incidence rates among children and adults (aged <60 years) with a history of natural varicella are influenced primarily by the frequency of exogenous exposures, while asymptomatic endogenous reactivations help to cap the rate at approximately 550 cases/100,000 person-years when exogenous boosting becomes rare. The Antelope Valley Varicella Active Surveillance Project was funded by the Centers for Disease Control and Prevention in 1995 to monitor the effects of varicella vaccination in one of the three representative regions of the United States. The stability in the data collection and number of reporting sites under varicella surveillance from 1995-2002 and HZ surveillance during 2000-2001 and 2006-2007 contributed to the robustness of the discerned trends. DISCUSSION: Varicella vaccination may be useful for leukemic children; however, the target population in the United States is all children. Since the varicella vaccine inoculates its recipients with live, attenuated varicella-zoster virus (VZV), clinical varicella cases have dramatically declined. Declining exogenous exposures (boosts) from children shedding natural VZV have caused waning cell-mediated immunity. Thus, the protection provided by varicella vaccination is neither lifelong nor complete. Moreover, dramatic increases in the incidence of adult shingles cases have been observed since HZ was added to the surveillance in 2000. In 2013, this topic is still debated and remains controversial in the United States. SUMMARY: When the costs of the booster dose for varicella and the increased shingles recurrences are included, the universal varicella vaccination program is neither effective nor cost-effective.

Review of the United States universal varicella vaccination program: Herpes zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily on the Antelope Valley Varicella Active Surveillance Project data.

In a cooperative agreement starting January 1995, prior to the FDA's licensure of the varicella vaccine on March 17, the Centers for Disease Control and Prevention (CDC) funded the Los Angeles Department of Health Services' Antelope Valley Varicella Active Surveillance Project (AV-VASP). Since only varicella case reports were gathered, baseline incidence data for herpes zoster (HZ) or shingles was lacking. Varicella case reports decreased 72%, from 2834 in 1995 to 836 in 2000 at which time approximately 50% of children under 10 years of age had been vaccinated. Starting in 2000, HZ surveillance was added to the project. By 2002, notable increases in HZ incidence rates were reported among both children and adults with a prior history of natural varicella. However, CDC authorities still claimed that no increase in HZ had occurred in any US surveillance site. The basic assumptions inherent to the varicella cost-benefit analysis ignored the significance of exogenous boosting caused by those shedding wild-type VZV. Also ignored was the morbidity associated with even rare serious events following varicella vaccination as well as the morbidity from increasing cases of HZ among adults. Vaccine efficacy declined below 80% in 2001. By 2006, because 20% of vaccinees were experiencing breakthrough varicella and vaccine-induced protection was waning, the CDC recommended a booster dose for children and, in 2007, a shingles vaccination was approved for adults aged 60 years and older. In the prelicensure era, 95% of adults experienced natural chickenpox (usually as children)-these cases were usually benign and resulted in long-term immunity. Varicella vaccination is less effective than the natural immunity that existed in prevaccine communities. Universal varicella vaccination has not proven to be cost-effective as increased HZ morbidity has disproportionately offset cost savings associated with reductions in varicella disease. Universal varicella vaccination has failed to provide long-term protection from VZV disease.

A significant dose-dependent relationship between mercury exposure from dental amalgams and kidney integrity biomarkers: a further assessment of the Casa Pia children's dental amalgam trial.

Dental amalgams are a commonly used dental restorative material. Amalgams are about 50% mercury (Hg), and Hg is known to significantly accumulate in the kidney. It was hypothesized that because Hg accumulates in the proximal tubules (PTs), glutathione-S-transferases (GST)-α (suggestive of kidney damage at the level of PT) would be expected to be more related to Hg exposure than GST-π (suggestive of kidney damage at the level of the distal tubules). Urinary biomarkers of kidney integrity were examined in children of 8-18 years old, with and without dental amalgam fillings, from a completed clinical trial (parent study). Our study determined whether there was a significant dose-dependent correlation between increasing Hg exposure from dental amalgams and GST-α and GST-π as biomarkers of kidney integrity. Overall, the present study, using a different and more sensitive statistical model than the parent study, revealed a statistically significant dose-dependent correlation between cumulative exposure to Hg from dental amalgams and urinary levels of GST-α, after covariate adjustment; where as, a nonsignificant relationship was observed with urinary levels of GST-π. Furthermore, it was observed that urinary GST-α levels increased by about 10% over the 8-year course of the study among individuals with an average exposure to amalgams among the study subjects from the amalgam group, in comparison with study subjects with no exposure to dental amalgams. The results of our study suggest that dental amalgams contribute to ongoing kidney damage at the level of the PTs in a dose-dependent fashion.

A dose-dependent relationship between mercury exposure from dental amalgams and urinary mercury levels: a further assessment of the Casa Pia Children's Dental Amalgam Trial.

Dental amalgams are a commonly used dental restorative material, and amalgams are about 50% mercury (Hg). In our study, urinary Hg levels was examined in children of age 8-18 years, with and without dental amalgam fillings, from a completed clinical trial (parent study) that was designed to evaluate the potential health consequences of prolonged exposure to Hg from dental amalgam fillings. Our study was designed to determine whether there was a significant dose-dependent correlation between increasing Hg exposure from dental amalgams and urinary Hg levels. Hg exposure depends on the size and number of teeth with dental amalgams. Overall, consistent with the results observed in the parent study, there was a statistically significant dose-dependent correlation between cumulative exposure to Hg from dental amalgams and urinary Hg levels, after covariate adjustment. Further, it was observed that urinary Hg levels increased by 18% to 52% among 8 to 18 year old individuals, respectively, with an average exposure to amalgams, in comparison to study subjects with no exposure to amalgams. The results of our study suggest that dental amalgams contribute to ongoing Hg exposure in a dose-dependent fashion.

Mitochondrial dysfunction, impaired oxidative-reduction activity, degeneration, and death in human neuronal and fetal cells induced by low-level exposure to thimerosal and other metal compounds.

Thimerosal (ethylmercurithiosalicylic acid), an ethylmercury (EtHg)-releasing compound (49.55% mercury (Hg)), was used in a range of medical products for more than 70 years. Of particular recent concern, routine administering of Thimerosal-containing biologics/childhood vaccines have become significant sources of Hg exposure for some fetuses/infants. This study was undertaken to investigate cellular damage among in vitro human neuronal (SH-SY-5Y neuroblastoma and 1321N1 astrocytoma) and fetal (nontransformed) model systems using cell vitality assays and microscope-based digital image capture techniques to assess potential damage induced by Thimerosal and other metal compounds (aluminum (Al) sulfate, lead (Pb)(II) acetate, methylmercury (MeHg) hydroxide, and mercury (Hg)(II) chloride) where the cation was reported to exert adverse effects on developing cells. Thimerosal-associated cellular damage was also evaluated for similarity to pathophysiological findings observed in patients diagnosed with autistic disorders (ADs). Thimerosal-induced cellular damage as evidenced by concentration- and time-dependent mitochondrial damage, reduced oxidative-reduction activity, cellular degeneration, and cell death in the in vitro human neuronal and fetal model systems studied. Thimerosal at low nanomolar (nM) concentrations induced significant cellular toxicity in human neuronal and fetal cells. Thimerosal-induced cytoxicity is similar to that observed in AD pathophysiologic studies. Thimerosal was found to be significantly more toxic than the other metal compounds examined. Future studies need to be conducted to evaluate additional mechanisms underlying Thimerosal-induced cellular damage and assess potential co-exposures to other compounds that may increase or decrease Thimerosal-mediated toxicity.

A comprehensive review of mercury provoked autism.

Emerging evidence supports the theory that some autism spectrum disorders (ASDs) may result from a combination of genetic/biochemical susceptibility, specifically a reduced ability to excrete mercury (Hg), and exposure to Hg at critical developmental periods. Elemental/inorganic Hg is released into the air/water where it becomes methylated and accumulates in animal tissues. The US population is primarily exposed to methyl-Hg by fish consumption. In addition, many pharmaceuticals have been, and some continue to be, a ubiquitous source of danger because they contain mercurials. Mercurials may be found in drugs for the eye, ear, nose, throat, and skin; in bleaching creams; as preservatives in cosmetics, tooth pastes, lens solutions, vaccines, allergy test and immunotherapy solutions; in antiseptics, disinfectants, and contraceptives; in fungicides and herbicides; in dental fillings and thermometers; and many other products. Hg has been found to cause immune, sensory, neurological, motor, and behavioural dysfunctions similar to traits defining/associated with ASDs, and that these similarities extend to neuroanatomy, neurotransmitters, and biochemistry. Furthermore, a review of molecular mechanisms indicates that Hg exposure can induce death, disorganization and/or damage to selected neurons in the brain similar to that seen in recent ASD brain pathology studies, and this alteration may likely produce the symptoms by which ASDs are diagnosed. Finally, a review of treatments suggests that ASD patients who undergo protocols to reduce Hg and/or its effects show significant clinical improvements in some cases. In conclusion, the overwhelming preponderance of the evidence favours acceptance that Hg exposure is capable of causing some ASDs.

Effect of phenethyl isothiocyanate on the metabolism of tobacco-specific nitrosamines by cultured rat oral tissue.

The effect of phenethyl isothiocyanate (PEITC) on the metabolism of N'-nitrosonornicotine (NNN) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by cultured rat oral tissue was investigated. Two protocols were used. In one, oral tissue from untreated rats was cultured in the presence of 10 or 50 microM PEITC and either NNN or NNK. The levels of NNN and NNK metabolites released into the culture media were determined by HPLC analysis. The presence of 10 microM PEITC inhibited the formation of all NNN metabolites from 45 to 70% when the concentration of NNN was 1 microM or 10 microM. When the concentration of PEITC was 50 microM the extent of inhibition was from 70 to 90%. alpha-Hydroxylation of NNK was inhibited 70 to 90% and N-oxidation of NNK was inhibited 80 to 90% by 10 microM PEITC. Carbonyl reduction of NNK to NNAL was unaffected by 10 microM PEITC and only slightly inhibited by 50 microM PEITC. In the second protocol, rats were fed NIH-07 diet containing 3 mumol PEITC/g for 1-14 days. The metabolism of NNN by cultured oral tissue from these rats was decreased from 40 to 90% relative to that by tissue from control rats. NNK metabolism was inhibited 40 to 60%. The extent of inhibition was the same when rats were fed PEITC containing diet for 1 or 14 days. NNN and NNK are the only tobacco constituents which induce oral cavity cancer in an animal model. The results of this study suggest the possibility that PEITC may be useful as a chemopreventive agent for oral cavity cancer.

An evaluation of antithrombin III laboratory tests.

Three laboratory tests for the measurement of antithrombin III (AT III) were evaluated. The tests measured functional AT III in serum and plasma, and the third measured AT III antigen in plasma. Normal values for each method were obtained by testing samples from 20 normal subjects. Each test was then performed on specimens from 15 patients clinically suspected of having hypercoagulable states. Each determination was run in duplicate. The hypercoagulable states included disseminated intravascular coagulation, pulmonary embolism, and pregnancy. Two-thirds of these patients were found to have antithrombin III levels below the normal range by all three of the methods studied. Patients who had decreased AT III activity in the functional assays also had decreased AT III antigen.