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To outline key factors that contribute to oral health issues of refugees and asylum seekers and provide management strategies for dental providers to teach desensitization and fear reduction for this special population.We researched published literature in the PubMed database and incorporated lessons gained from treating refugee and asylee patients at a Vulnerable Populations Clinic (VPC) at an urban academic dental school. Refugees and asylees are at high risk for oral conditions due to a tendency to not seek routine dental treatment, psychological stressors, and various systemic factors. Oral health providers can teach patients desensitization and fear reduction by working to gain patients' trust by having effective communication and prioritizing comfort in the dental operatory. Providers should also utilize translation, psychological, and/or multicultural support services during their management of care.By having a stronger understanding of the key causes of oral health issues among refugees and asylees in the United States, dental providers can better approach managing care for this vulnerable patient population. The concepts of teaching desensitization and fear reduction utilized for this special population can be applied to managing care for the wider special needs patient community.

The coronavirus disease (COVID-19) pandemic has impacted the world in unprecedented ways. It is clear that this pandemic, unlike any public health challenge in recent memory, has the potential to fundamentally alter the delivery of many healthcare services, including dentistry. As evidence-based information on COVID-19 continues to emerge, this article serves as a means to disseminate current opinions, management strategies, and the impact of COVID-19 on dentistry.

Recent studies have suggested that among those receiving seasonal influenza vaccine (SIV), reduced immunogenicity is observed in recently vaccinated (RV; within the past season or 2) persons when compared with those not recently vaccinated (NRV). We performed a meta-analysis to assess the effect of recent immunization with SIV on serum H5 hemagglutination inhibition (HAI) antibody responses after influenza A/H5N1 vaccination using data from a series of randomized controlled trials. The primary outcome was seroconversion measured by HAI assays following receipt of 2 doses of H5N1 vaccine. The geometric mean titer (GMT) of serum HAI antibody after vaccination was the secondary outcome. Analyses were performed using propensity score (PS) matching. The PS for each individual in the meta-analysis cohort was calculated using logistic regression and covariates included age, gender, race, antigen dose, adjuvant, statin use and vaccine manufacturer. 2015 subjects enrolled in 7 clinical trials were eligible for inclusion in the meta-analysis cohort; among these, 915 (45%) were RV. 901 RV subjects were matched (1:1) with replacement to a subject who was NRV. Subjects who received SIV within the previous season were significantly less likely to seroconvert following H5N1 vaccination (adjusted odds ratio 0.76; 95%CI 0.60–0.96; p = 0.024), and the GMT was 18% higher among NRV subjects (GM ratio of HAI antibody 1.18; 95%CI 1.04–1.33; p = 0.008). Further work is needed to better define the effects of, and mechanisms contributing to, reduced immune responses to H5N1 vaccine among RV subjects.

Der wahre Wert des Internet der Dinge (Internet of Things, IoT) liegt in seinen Daten. In der Tat ist der Hauptgrund fur die Vernetzung der IoT-Gerate das Erzeugen grosen Datenmengen, die von anderen Geraten, Anwendungen, Maschinen oder Menschen analysiert werden konnen, um gegebenenfalls darauf zu reagieren. Die Integration von IoMT-Daten mit Uberwachungs-, Warnungs- und Entscheidungshilfesystemen wird eine dramatische Transformation bei der Entwicklung und Herstellung effektiver und sicherer medizinischer Produkte ermoglichen und die Einfuhrung einer wertorientierten Gesundheitsversorgung und personalisierten Medizin beschleunigen.

BACKGROUND Syphilis management is complex and demonstration of treatment response requires monitoring of nontreponemal antibody titers for a ≥ 4-fold decline and/or seroreversion to nonreactive titers. METHODS We evaluated data from a multicenter clinical trial of syphilis treatment conducted from 2000 to 2009 involving human immunodeficiency virus (HIV)-negative patients 18 years or older with early syphilis. To assess the rate of titer decline and seroreversion after effective therapy, rapid plasma reagin (RPR) titers were analyzed at 1, 3, 6, 9, and 12 months among patients with an appropriate treatment response. We plotted the rate of RPR titer decline after treatment, estimated the frequency of seroreversion, and conducted multivariate analyses to assess characteristics associated with seroreversion. RESULTS Among 369 (79.4%) of 465 HIV-negative patients with early syphilis who had an appropriate treatment response, 333 participants had complete RPR data over 12 months. Although the decline in RPR titers was ≥ 4-fold among 88.0% (293/333) of participants at 3 months and ≥ 8-fold among 77.8% at 6 months, only 9.6% achieved complete RPR seroreversion at 6 months and 17.1% at 12 months after therapy. Male sex (adjusted odds ratio, 4.3; 95% confidence interval, 1.8-10.5) and baseline RPR titers ≤ 1:32 (adjusted odds ratio, 14.5; 95% confidence interval, 6.8-31.2) were associated with higher odds of seroreversion compared with females and titers > 1:32, respectively. CONCLUSIONS Despite a ≥ 4-fold RPR titer decline after treatment, the majority of HIV-negative patients with early syphilis failed to have seroreversion at 12 months. Nontreponemal antibody titers often persist despite an appropriate treatment response.

Background In the United States, seasonal inactivated influenza vaccine (IIV) is recommended for pregnant women; however, in early 2009, immunization rates were low, partly due to limited prospective data and concerns about vaccine safety. Objective We conducted a randomized study of two licensed seasonal trivalent IIVs (IIV3) to assess their safety and immunogenicity in pregnant women. Study Design In this prospective, randomized clinical study, 100 pregnant women, 18–39 years of age and ≥14 weeks gestation received a single intramuscular dose of 2008–2009 Fluzone® or Fluarix®. Injection site and systemic reactions were recorded for 7 days after vaccination and serious adverse events (SAEs) and pregnancy outcomes were documented. Serum samples collected before and 28 days after vaccination were tested for hemagglutination inhibition (HAI) antibody levels. Results The majority of the injection site and systemic reactions were mild and self-limited after both vaccines. No fever ≥100 °F was reported. There were no vaccine-associated SAEs. Immune responses to influenza vaccine antigens were similar for the two study vaccines, with robust HAI responses against influenza A strains, and relatively lower responses for influenza B strains. Conclusion Seasonal inactivated influenza vaccines were well tolerated and immunogenic in pregnant women. ClinicalTrials.gov identifier NCT00905125. Synopsis: In this prospective clinical trial, we demonstrated that immunization with seasonal trivalent, inactivated influenza vaccine in the second and third trimester of pregnancy is immunogenic and safe.

Background Live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) are both licensed for administration to nursing mothers. Little is known about the potential for transmission of LAIV viruses from the mother to the infant and the comparative breast milk antibody responses to LAIV and IIV. Methods We performed a randomized, double-blind study comparing the immunogenicity of LAIV to IIV when administered to nursing mothers. The safety of LAIV to IIV in women and their infants was also compared. Women received LAIV + intramuscular placebo, or IIV + intranasal placebo on Day 0. Breast milk and nasal swabs (from women and infants) were collected on Days 0, 2, and 8 for detection of LAIV. Breast milk and serum antibody responses were measured at Days 0 and 28. The primary hypothesis was that LAIV would provide superior induction of breast milk IgA responses to influenza as compared to IIV when administered to nursing mothers. Results Breast milk IgG, breast milk IgA (H1N1 only), serum hemagglutination inhibition (HAI), and serum IgG responses were significantly higher following administration of IIV compared to LAIV. Receipt of either LAIV or IIV was safe in women and their infants. One (1%) LAIV recipient transmitted vaccine virus to her infant who remained well. No influenza virus was detected in breast milk. Conclusions Breast milk and serum antibody responses were higher for IIV compared to LAIV. LAIV and IIV were safe for nursing women but there was one (1%) possible transmission of LAIV to an infant. This study suggests that IIV may be the preferred vaccine for nursing mothers.

During the 2009 influenza pandemic both seasonal and 2009 pandemic vaccines were recommended. We conducted a randomized trial of monovalent 2009-H1N1 vaccine and seasonal trivalent inactivated influenza vaccine (IIV3) given sequentially or concurrently to adults.Adults randomized to 4 study groups and stratified by age (18-64 and ≥65 years) received 1 dose of seasonal IIV3 or placebo and 2 doses of 2009-H1N1 vaccine or placebo in one of 4 combinations, i.e., H1N1+Placebo/H1N1+Placebo/IIV3 (HP/HP/V3), H1N1+IIV3/H1N1+Placebo/Placebo (HV3/HP/P), H1N1+Placebo/H1N1+IIV3/Placebo (HP/HV3/P), and IIV3+Placebo/H1N1+Placebo/H1N1 (V3P/HP/H). Intramuscular injections were given three times at 21 day intervals. Sera for antibody assays were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored.Eight hundred-five (805) adults were enrolled. All combinations of vaccines were safe and well tolerated. In general, one dose of 2009-H1N1 and one dose of IIV3, regardless of sequence or concurrency of administration, were immunogenic in adults. There were no significant differences in geometric mean titers (GMT) or the proportions of subjects with ≥4-fold rise in antibody responses and titers ≥40 for any vaccine group or between age strata for 2009-H1N1 after the first or second dose, although the vaccine sequence affected the titers to the IIV3 antigens. Hemagglutination inhibition antibody (HAI) GMTs against 2009-H1N1 for the combined age strata 21 days after the first 2009-H1N1 dose were 190.4, 182.1, 232.9 and 157.5 for HP/HP/V3, HV3/HP/P, HP/HV3/P and V3P/HP/H, respectively. While IIV3 GMTs were adequate they were generally lower than the 2009-H1N1 GMTs. In a subset of subjects, there was good correlation between HAI and microneutralization (MN) titers (Spearman's correlation coefficient 0.92).All vaccine combinations were generally well tolerated. Immune responses to one dose of 2009-H1N1 were adequate regardless of the sequence of vaccination in all age groups, but the sequence affected titers to IIV3 antigens.

As the influenza A H1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years.Children received 2 doses of approximately 15 or 30 µg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition titers were measured on days 0 (prevaccination), 8, 21, 29 and 42.A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 µg dosage elicited a seroprotective hemagglutination inhibition (≥ 1:40) in 20%, 47% and 93% of children in the 6-35 month, 3-9 year and 10-17 year age strata 21 days after dose 1 and in 78%, 82% and 98% of children 21 days after dose 2, respectively. The 30 µg vaccine dosage induced similar responses.The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 µg dose induced seroprotective antibody responses in most children 10-17 years of age, younger children required 2 doses, even when receiving dosages 4- to 6-fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics.

Background. Children 6 through 35 months of age are recommended to receive half the dose of influenza vaccine compared with older children and adults. Methods. This was a 6-site, randomized 2:1, double-blind study comparing full-dose (0.5 mL) trivalent inactivated influenza vaccine (TIV) with half-dose (0.25 mL) TIV in children 6 through 35 months of age. Children previously immunized with influenza vaccine (primed cohort) received 1 dose, and those with no previous influenza immunizations (naive cohort) received 2 doses of TIV. Local and systemic adverse events were recorded. Sera were collected before immunization and 1 month after last dose of TIV. Hemagglutination inhibition antibody testing was performed. Results. Of the 243 subjects enrolled (32 primed, 211 naive), datafor 232 were available forcomplete analysis. No significant differences in local or systemic reactions were observed. Few significant differences in immunogenicity to the 3 vaccine antigens were noted. The immune response to H1N1 was significantly higher in the full-dose group among primed subjects. In the naive cohort, the geometric mean titer for all 3 antigens after 2 doses of TIV were significantly higher in the 12 through 35 months compared with the 6 through 11 months age group. Conclusions. Our study confirms the safety of full-dose TIV given to children 6 through 35 months of age. An increase in antibody responses after full- versus half-dose TIV was not observed, except for H1N1 in the primed group. Larger studies are needed to clarify the potential for improved immunogenicity with higher vaccine doses. Recommending the same dose could simplify the production, storage, and administration of influenza vaccines.

In 2005, New York University Colleges of Dentistry and Nursing formed an organizational partnership to create a unique model of interprofessional education, research, service and practice. This paper describes the first eight years of experience, from the early reaction of the public to the partnership, to examples of success and past and current challenges.

Administering 2 separate vaccines for seasonal and pandemic influenza was necessary in 2009. Therefore, we conducted a randomized trial of monovalent 2009 H1N1 influenza vaccine (2009 H1N1 vaccine) and seasonal trivalent inactivated influenza vaccine (TIV; split virion) given sequentially or concurrently in previously vaccinated children.Children randomized to 4 study groups and stratified by age received 1 dose of seasonal TIV and 2 doses of 2009 H1N1 vaccine in 1 of 4 combinations. Injections were given at 21-day intervals and serum samples for hemagglutination inhibition antibody responses were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored.All combinations of vaccines were safe in the 531 children enrolled. Generally, 1 dose of 2009 H1N1 vaccine and 1 dose of TIV, regardless of sequence or concurrency of administration, was immunogenic in children ≥ 10 years of age; children10 years of age required 2 doses of 2009 H1N1 vaccine.Vaccines were generally well tolerated. The immune responses to 2009 H1N1 vaccine were adequate regardless of the sequence of vaccination in all age groups but the sequence affected titers to TIV antigens. Two doses of 2009 H1N1 vaccine were required to achieve a protective immune response in children10 years of age.NCT00943202.

The influenza A/H1N1 pandemic in 2009 created an urgent need to develop vaccines for mass immunization. To guide decisions regarding the optimal immunization dosage and schedule for adults, we evaluated two monovalent, inactivated, unadjuvanted H1N1 influenza vaccines in independent, but simultaneously conducted, multi-center Phase 2 trials of identical design.Healthy adults, stratified by age (18-64 years and ≥65 years), were randomized (1:1 allocation), in a double-blind, parallel-group design, to receive two intramuscular doses (21 days apart) of vaccine containing approximately 15 μg or 30 μg of hemagglutinin (HA). Primary endpoints were safety (reactogenicity for 8 days after each vaccination and vaccine-associated serious adverse events during the 7 month study) and immunogenicity (proportion of subjects, stratified by age, achieving a serum hemagglutination inhibition [HI] antibody titer ≥1:40 or a ≥4-fold rise in titer after a single injection of either dosage).Both vaccines were well-tolerated. A single 15 μg dose induced HI titers ≥1:40 in 90% of younger adults (95% confidence interval [CI] 82-95%) and 81% of elderly (95% CI 71-88%) who received Sanofi-Pasteur vaccine (subsequently found to contain 24 μg HA in the standard potency assay), and in 80% of younger adults (95% CI 71-88%) and 60% of elderly (95% CI 50-70%) who received CSL vaccine. Both vaccines were significantly more immunogenic in younger compared with elderly adults by at least one endpoint measure. Increasing the dose to 30 μg raised the frequency of HI titers ≥1:40 in the elderly by approximately 10%. Higher dosage did not significantly enhance immunogenicity in younger adults and a second dose provided little additional benefit to either age group.These trials provided evidence for policymakers that a single 15 μg dose of 2009 A/H1N1 vaccine would likely protect most U.S. adults and suggest a potential benefit of a 30 μg dose for the elderly.

The aim of the study was to determine whether reduced doses of trivalent inactivated influenza vaccine (TIV) administered by the intradermal (ID) route generated similar immune responses to standard TIV given intramuscularly (IM) with comparable safety profiles. Recent changes in immunization recommendations have increased the number of people for whom influenza vaccination is recommended. Thus, given this increased need and intermittent vaccine shortages, means to rapidly expand the vaccine supply are needed. Previously healthy subjects 18-64 years of age were randomly assigned to one of four TIV vaccine groups: standard 15 μg HA/strain TIV IM, either 9 μg or 6 μg HA/strain of TIV ID given using a new microinjection system, (BD Soluvia™ Microinjection Systema), or 3 μg HA/strain of TIV ID given by Mantoux technique. All vaccines contained A/New Caledonia (H1N1), A/Wyoming (H3N2) and B/Jiangsu strains of influenza. Sera were obtained 21 days after vaccination and hemagglutination inhibition (HAI) assays were performed and geometric mean titers (GMT) were compared among the groups. Participants were queried immediately following vaccination regarding injection pain and quality of the experience. Local and systemic reactions were collected for 7 days following vaccination and compared. Ten study sites enrolled 1592 subjects stratified by age; 18-49 years, [N=814] and 50-64 years, [N=778]. Among all subjects, for each of the three vaccine strains, the GMTs at 21 days post-vaccination for both the 9 μg and the 6 μg doses of each strain given ID were non inferior to GMTs generated after standard 15 μg doses/strain IM. However, for the 3 μg ID dose, only the A/Wyoming antigen produced a GMT that was non-inferior to the standard IM dose. Additionally, in the subgroup of subjects 50-64 years of age, the 6 μg dose given ID induced GMTs that were inferior to the standard IM TIV for the A/H1N1 and B strains. No ID dose produced a GMT superior to that seen after standard IM TIV. Local erythema and swelling were significantly more common in the ID groups but the reactions were mild to moderate and short-lived. No significant safety issues related to intradermal administration were identified. Participants given TIV ID provided favorable responses to questions about their experiences with ID administration. In conclusion, for the aggregated cohorts of adults 18 to 64 years of age, reduced doses (6 μg and 9 μg) of TIV delivered ID using a novel microinjection system stimulated comparable HAI antibody responses to standard TIV given IM. The reduced 3 μg dose administered ID by needle and syringe, as well as the 6 μg ID for subjects aged 50-64 years of age generated poorer immune responses as compared to the 15 μg IM dose.

The Oulipian idea of potential literature presents a conundrum vis-a-vis authorship. The group's early theoretical texts emphasized an experimental, quasi-scientific approach to writing that anyone...

The International Caries Classification and Management System (ICCMS™) is a comprehensive set of clinical protocols that address all diagnostic, preventive and restorative decisions necessary “to preserve tooth structure and restore only when indicated,” which is the mission adopted at the Temple University Caries Management Pathways workshop, in 2012 [1]. The foundation for ICCMS™ is based on extensive critical analyses, research, and clinical feedback on the best approaches to move away from the mechanical or restorative care that has been followed around the world, towards a system where prevention is emphasized, initial caries lesions are prevented from progressing (controlled), and moderate or extensive caries lesions are restored with the goal of preserving, as much as possible, natural tooth structure [2]. This chapter will describe the scientific, and clinical management protocols that have been developed over the last several years by over 70 cariologists, epidemiologists, and clinicians. While ICCMS™ is recommended as the most comprehensive pathway for caries management to achieve the desired aforementioned mission, it is important to emphasize that ICCMS™ is not the only system available today that promotes staging of the caries process and risk assessment and management [1]. The ICCMS™, in contrast to other systems, has well-developed and documented protocols for the implementation of a new model of caries management. It is based on the well-established and widely used International Caries Detection and Assessment System (ICDAS™).

BACKGROUND Influenza-virus hemagglutinin (HA) protein expressed in insect cells by recombinant baculovirus is a candidate influenza vaccine. METHODS In a randomized, double-blind trial conducted in 399 adults > or = 65 years of age, the efficacy of trivalent inactivated influenza vaccine (TIV) licensed for intramuscular injection was compared with that of trivalent baculovirus-expressed HA vaccine administered at doses of 15 microg, 45 microg, or 135 microg of each HA. RESULTS Compared with TIV, baculovirus-expressed HA vaccine was safe and induced better serum antibody responses to the H3 component when administered at doses of 45 microg or 135 microg of each HA. CONCLUSIONS Baculovirus-expressed HA is a safe and immunogenic influenza vaccine in elderly adults.

Influenza A (H5N1) viruses could cause a severe worldwide epidemic, with high attack rates, large numbers of deaths and hospitalizations, and wide disruption. Effective vaccines against these viruses in humans are urgently needed.We conducted a multicenter, double-blind two-stage study involving 451 healthy adults 18 to 64 years of age who were randomly assigned in a 2:2:2:2:1 ratio to receive two intramuscular doses of a subvirion influenza A (H5N1) vaccine of 90, 45, 15, or 7.5 microg of hemagglutinin antigen or placebo. The subjects were followed for the safety analysis for 56 days. Serum samples obtained before each vaccination and again 28 days after the second vaccination were tested for H5 antibody by microneutralization and hemagglutination inhibition.Mild pain at the injection site was the most common adverse event for all doses of vaccine. The frequency of a serum antibody response was highest among subjects receiving doses of 45 microg or 90 microg. Among those who received two doses of 90 microg, neutralization antibody titers reached 1:40 or greater in 54 percent, and hemagglutination-inhibition titers reached 1:40 or greater in 58 percent. Neutralization titers of 1:40 or greater were seen in 43 percent, 22 percent, and 9 percent of the subjects receiving two doses of 45, 15, and 7.5 microg, respectively. No responses were seen in placebo recipients.A two-dose regimen of 90 mug of subvirion influenza A (H5N1) vaccine does not cause severe side effects and, in the majority of recipients, generates neutralizing antibody responses typically associated with protection against influenza. A conventional subvirion H5 influenza vaccine may be effective in preventing influenza A (H5N1) disease in humans. (ClinicalTrials.gov number, NCT00115986.).

Persistent nontreponemal titers after treatment are common among patients with early syphilis. We retreated 82 human immunodeficiency virus–negative early syphilis participants who were serofast at 6 months using benzathine penicillin. Only 27% exhibited serological response after retreatment and after an additional 6 months of follow-up.

Background Serologic tests for syphilis results at the time of diagnosis are the basis for evaluating response to syphilis therapy. After treatment, however, serologic tests for syphilis titers may continue to increase for several weeks. We evaluated rapid plasma reagin (RPR) titer variation during the 14 days after therapy using data from a recent large, prospective randomized controlled trial. Methods Prospectively enrolled participants in North America and Madagascar with primary, secondary, or early latent syphilis were randomly assigned to penicillin, doxycycline (in the case of penicillin allergy), or azithromycin treatment. Blood for RPR analysis was drawn at days 0, 7, and 14 posttreatment. All RPR titers were determined simultaneously at a central laboratory. Results Four hundred and seventy patients had data available for at least 2 of 3 RPR measurements. Overall, 20% of patients showed a titer increase of at least 1 dilution in the 14 days after therapy. The greatest proportion of titer increases following therapy was observed in patients with primary syphilis. Comparing outcome of therapy using the initial (day 0) RPR titer versus the maximal RPR titer (during 14 days) resulted in outcome reclassification in 2.98% of participants. Conclusions Despite the fact that about 20% of early syphilis patients had increases in RPR titers immediately after treatment, these changes rarely influenced assessment of therapeutic outcome. Only 3% of patients treated would have been reclassified.

Objective. To provide additional information on the safety of trivalent, cold-adapted influenza vaccine (CAIV-T) in children. Methods. Children 15 to 71 months of age were enrolled in a multicenter, prospective, randomized, double-blind, and placebo-controlled trial to receive by nasal spray CAIV-T or placebo. In year 1 (1996–1997), 1314 were enrolled in the 2-dose cohort and 288 were enrolled in the 1-dose cohort. In year 2 (1997–1998), 1358 of the original participants received 1 dose of vaccine or placebo according to their original treatment group assignment. In year 3 (1998–1999) and year 4, the trial continued as an open-label safety trial of CAIV-T. A total of 642 and 549 children enrolled in years 3 and 4, respectively, received their third and fourth sequential annual doses of CAIV-T. Measured were 1) the occurrence of specific respiratory, gastrointestinal and systemic symptoms, unexpected symptoms (not specified in the diary card), and use of medications within the first 10 days after vaccination; 2) the occurrence of an acute illness and use of medication within 11 to 42 days after vaccination; and 3) the occurrence of serious adverse events within 42 days after vaccination. Results. The adjusted odd ratios of specific respiratory and gastrointestinal symptoms during the 10 days after vaccination were determined in years 1 and 2. Runny nose or nasal congestion, vomiting, muscle aches, and fever were significantly associated with the first dose of CAIV-T. With the second dose, runny nose was the only symptom that was associated with CAIV-T. In year 2, CAIV-T did not cause excess in any of the specific respiratory and gastrointestinal symptoms. In years 3 and 4, specific respiratory and gastrointestinal symptoms were comparable to that observed in year 2. A CAIV-T–associated symptom was most likely to occur on day 2 with the first dose of vaccine. The occurrence of unexpected symptoms was primarily of the gastrointestinal system. Approximately 6% of CAIV-T and 3.6% of placebo recipients had a gastrointestinal symptom. CAIV-T seemed to be associated with a mild excess in abdominal pain and vomiting only with the first vaccine dose. A statistically significant increase in the use of analgesics/antipyretics was detected only with the first dose in CAIV-T vaccinees compared with placebo recipients (23.5% vs 16.6%). Between days 11 and 42, CAIV-T use was not associated with an excess of illness, otitis media, or use of medication. None of the 6 serious adverse events in CAIV-T recipients in years 1 to 4 was attributed to the vaccine. Conclusions. CAIV-T was safe in children. Mild respiratory, gastrointestinal, and systemic symptoms of short duration were observed in a minority of children and primarily with the first vaccine dose. Sequential annual doses of CAIV-T were well tolerated.

We conducted a double-blind, randomized trial of three dilutions of vaccinia virus vaccine in previously unimmunized adults in order to assess the clinical success rates, humoral responses, and virus-specific activity of cytotoxic T cells and interferon-gamma-producing T cells.Sixty healthy adults were inoculated intradermally by bifurcated needle with undiluted vaccine (dose, 10(7.8) plaque-forming units [pfu] per milliliter), a 1:10 dilution (dose, 10(6.5) pfu per milliliter), or a 1:100 dilution (dose, 10(5.0) pfu per milliliter); there were 20 subjects in each group. The subjects were monitored with respect to vesicle formation (an indicator of successful vaccination), the viral titer at the time of peak lesion formation, antiviral antibodies, and cellular immune responses.A vaccinia vesicle developed in 19 of the 20 subjects who received undiluted vaccine (95 percent), 14 of the 20 who received the 1:10 dilution (70 percent), and 3 of the 20 who received the 1:100 dilution (15 percent). One month after vaccination, 34 of 36 subjects with vesicles had antibody responses, as compared with only 1 of 24 subjects without clinical evidence of vaccinia virus replication. Vigorous cytotoxic T-cell and interferon-gamma responses occurred in 94 percent of subjects with vesicles, and a cytotoxic T-cell response occurred in only one subject without a vesicle.The vaccinia virus vaccine (which was produced in 1982 or earlier) still has substantial potency when administered by a bifurcated needle to previously unvaccinated adults. Diluting the vaccine reduces the rate of successful vaccination. The development of vesicular skin lesions after vaccination correlates with the induction of the antibody and T-cell responses that are considered essential for clearing vaccinia virus infections.

To evaluate the potential to increase the supply of smallpox vaccine (vaccinia virus), we compared the response to vaccination with 10(8.1), 10(7.2), and 10(7.0) plaque-forming units (pfu) of vaccinia virus per milliliter.In this randomized, single-blind, prospective study, 680 adults who had not been previously immunized were inoculated intradermally with undiluted vaccine (mean titer, 10(8.1) pfu per milliliter), a 1:5 dilution, or a 1:10 dilution of vaccinia virus with use of a bifurcated needle, and the site was covered with a semipermeable dressing. Subjects were monitored for vesicle formation (an indicator of the success of vaccination) and adverse events for 56 days after immunization.Success rates did not differ significantly among the groups and ranged from 97.1 to 99.1 percent after the first vaccination. Both the undiluted and diluted vaccines were reactogenic. In addition to the formation of pustules, common adverse events included the formation of satellite lesions, regional lymphadenopathy, fever, headache, nausea, muscle aches, fatigue, and chills consistent with the presence of an acute viral illness. Generalized and localized rashes, including two cases of erythema multiforme, were also observed.When given by a bifurcated needle, vaccinia virus vaccine can be diluted to a titer as low as 10(7.0) pfu per milliliter (approximately 10,000 pfu per dose) and induce local viral replication and vesicle formation in more than 97 percent of persons.

Because of delays in the manufacturing of the 2000-2001, trivalent inactivated influenza vaccine in the US, there were concerns that there might be shortages of vaccine supply in the US, Therefore, we conducted a prospective, randomized, open-label, multicenter trial at six C academic medical centers in the US, to evaluate the immunogenicity of a half dose of inactivated vaccine in healthy adults. Healthy adults between the ages of 18 and 49 were randomized to receive either a full 0.5 ml (15.5 mug of each HA antigen) dose or a 0.25 ml (7.75 mug of each HA antigen) dose of the 2000-2001 trivalent inactivated influenza vaccine by intramuscular injection. Sera were obtained for assessment of hemagglutination-inhibiting antibody to each of the three strains contained in the vaccine before and 21 days after vaccination. The proportions of individuals achieving a post-vaccination titer of greater than or equal to1:40, the geometric mean titers (GMTs) of post-vaccination antibody, and the proportions of individuals with a four-fold or greater increase in antibody were lower for all three strains in those receiving 0.25 ml of vaccine compared to those receiving 0.5 ml. However, the differences were small for all three antigens. The upper 95% confidence limits for differences between 0.25 and 0.5 ml doses were less than 20% for rates of achieving a titer of greater than or equal to1:40 and four-fold response, and less than 1.5 for the ratios of GMTs between dose groups, for all three vaccine antigens. These results suggest that when vaccine is in short supply, a strategy using a half dose in healthy adults could increase the number of people vaccinated with relatively little adverse impact on vaccine immunogenicity. (C) 2002 Published by Elsevier Science Ltd.

The enduring pandemic threat of Avian influenza A/H5N1 was underscored in January 2014 when the first North American H5N1 death was documented in a Canadian who returned from China [1, 2]. For almost 2 decades preceding this fatality, the pandemic potential of avian H5N1 influenza has been of concern [3, 4]. More than 30 sporadic cases of H5N1 infection occurred in 2013, for a total of 648 laboratory-confirmed illnesses, and ∼60% mortality was reported to the World Health Organization by 16 countries from 2003 to 2013 [5]. The repeated outbreaks of novel and variant avian and swine influenza viruses in humans have led to efforts to produce vaccines against these pandemic or potential pandemic viruses. Clinical trials of candidate H5N1 vaccines revealed that these hemagglutinins (HAs) were poor vaccine antigens [6–8], but antibody responses could be improved substantially with adjuvants [9]. Because vaccine supplies may be limited, it is also important to lower the antigen dose required to induce protection in order to make limited vaccine supplies available for protection of more people. For stockpiled vaccine antigens that require an adjuvant to achieve protective antibody titers, 1 rapid response approach would be to match the relevant antigen to a stockpiled adjuvant at pandemic onset and mix the reagents at designated field sites—the mix-and-match approach tested here. The squalene-containing oil-in-water emulsion adjuvant, MF59, improved the antibody response, permitted dose sparing, and enhanced efficacy [10] when paired with inactivated influenza vaccines [11–14]. MF59-adjuvanted seasonal influenza vaccines were first licensed for the elderly [15] by the European Union in 1997 and—along with MF59-adjuvanted 2009 H1N1 pandemic vaccines—have subsequently been licensed in more than 30 countries with an excellent safety profile and over 65 million doses delivered [16]. MF59-adjuvanted vaccines have not been licensed in the United States. However, the US Department of Health and Human Services (HHS) Biomedical Advanced Research and Development Authority (BARDA) has procured in the National Pre-pandemic Influenza Vaccine Stockpile both H5N1 vaccines and the oil-in-water adjuvants MF59 and AS03. Here, we studied a mix-and-match tactic that paired a stockpiled H5N1 antigen from one manufacturer with stockpiled MF59 adjuvant from another manufacturer, and we demonstrated the potential of point-of-use mixing as a flexile logistical tactic for rapid deployment of stockpiled vaccine reagents should an H5N1 pandemic occur.

There has been substantial progress in approaches to prevent and treat human immunodeficiency virus type 1 (HIV-1) infection, but the need for a safe and effective HIV-1 vaccine remains a high global health priority [1–4]. However, very few HIV-1 vaccine trials have evaluated mucosal immune responses elicited by candidate vaccines in humans. In particular, it remains unclear whether intramuscular immunization can induce mucosal immune responses in humans. Mucosal sites represent the portal of entry for the majority of HIV-1 infections, and thus it would presumably be desirable to induce mucosal HIV-1–specific immune responses that may be able to block or attenuate infection. Limited data are currently available regarding the magnitude and phenotype of mucosal immune responses and immune activation following HIV-1 vaccination in humans [5]. This reflects logistic challenges associated with mucosal sampling and obtaining mucosal biopsies in the context of clinical vaccine studies as well as the immunologic challenges associated with accurately evaluating mucosal immune responses in humans. We have recently reported the first-in-human immunogenicity of a novel adenovirus serotype 26 (Ad26) vector expressing HIV-1 envelop (Env) [6, 7]. Ad26 exhibits lower seroprevalence and neutralizing antibody (NAb) titers compared with adenovirus serotype 5 (Ad5), particularly in the developing world [8, 9]. Moreover, Ad26 and Ad5 differ in terms of their basic virology, innate immune profiles, and adaptive immune phenotypes [10–14]. In addition, Ad26-based vaccine regimens have shown improved protection compared with Ad5 and DNA/Ad5 regimens in stringent SIVmac251 (simian immunodeficiency virus) challenge models in rhesus monkeys [15, 16]. In the present study, we explored mucosal immune responses and inflammation in humans following immunization with an Ad26 vector expressing clade A Env glycoprotein (gp) 140 (Ad26-EnvA) [6, 7] in baseline Ad26-seronegative and Ad26-seropositive subjects.

New York City has a large number of individuals seeking asylem who are victims of torture. In addition to dental needs, which include cases of severe trauma to the mouth, these individuasl require special support because of their fear of contact by those they do not know. A cooperative program between the New York University College of Dentistry and Bellevue NYU, known as the Program for Survivors of Torture, is described.

Obesity emerged as a risk factor for morbidity and mortality related to 2009 pandemic influenza A (H1N1) infection. However, few studies examine the immune responses to H1N1 vaccine among children and adults of various body mass indices (BMI). Pooling data from 3 trials of unadjuvanted split-virus H1N1 A/California/07/2009 influenza vaccines, we analyzed serologic responses of participants stratified by BMI grouping. A single vaccine dose produced higher hemagglutination inhibition antibody titers at day 21 in obese compared to nonobese adults, but there were no significant differences in responses to H1N1 vaccine among children or adults of various BMI following 2 doses.

Development of a preventive human immunodeficiency virus 1 (HIV-1) vaccine is a global health priority, but to our knowledge only 4 vaccine concepts have been evaluated in field trials to date [1–7]. Adenoviruses are potent vectors [8], and although recombinant adenovirus (Ad) serotype 5 (rAd5) vectors have been studied as preventative HIV-1 vaccines both alone and in conjunction with DNA priming, they have not been efficacious [1, 7]. Potential limitations of Ad serotype 5 (Ad5) vectors include the high level of preexisting antivector immunity, particularly in the developing world [9, 10], as well as qualitative features of the immune responses elicited [11]. To overcome these potential limitations, adenoviruses with lower seroprevalence have been proposed as vectors [12]. Alternative serotype Ad vectors have notable biologic differences from rAd5 in terms of baseline seroepidemiologic findings, receptor usage, tropism, innate immune profile, adaptive immune phenotype, and protective efficacy in the simian immunodeficiency virus (SIV)/macaque model [13–16]. Several alternative serotype Ad vectors, including Ad26 and Ad35, have advanced into clinical trials as potential vaccine vectors [17–20]. An alternative approach to retain favorable immunologic features of Ad5 vectors while reducing the potential impact of preexisting Ad5 antibodies is to develop chimeric recombinant Ad vectors in which the key Ad5 neutralization epitopes have been removed. Because Ad5-specific neutralizing antibodies (nAbs) are directed primarily against the Ad5 hexon major capsid protein [21], specifically against the 7 hexon hypervariable regions on the hexon surface, we developed chimeric rAd5 vectors in which the hexon hypervariable regions were swapped with the corresponding regions from the rare Ad serotype 48 (Ad48) [22]. These chimeric vectors use the same cellular receptor as Ad5 and effectively circumvented dominant Ad5-specific nAbs directed against the hexon hypervariable regions [22]. Furthermore, a single injection of an Ad5HVR48 chimeric vaccine expressing SIV Env/Gag/Pol/Nef was immunogenic and led to improved peak and plateau viral loads after SIV challenge in macaques [23]. In this study, we report the first-in-human safety and immunogenicity evaluation of an Ad5HVR48 vectored HIV-1 vaccine, and we evaluated the capacity of this chimeric vector to induce nAbs against both Ad5 and Ad48.

Background New tools are required for the diagnosis of pre-symptomatic leprosy towards further reduction of disease burden and its associated reactions. To address this need, two new skin test antigens were developed to assess safety and efficacy in human trials. Methods A Phase I safety trial was first conducted in a non-endemic region for leprosy (U.S.A.). Healthy non-exposed subjects (n = 10) received three titrated doses (2.5 µg, 1.0 µg and 0.1 µg) of MLSA-LAM (n = 5) or MLCwA (n = 5) and control antigens [Rees MLSA (1.0 µg) and saline]. A randomized double blind Phase II safety and efficacy trial followed in an endemic region for leprosy (Nepal), but involved only the 1.0 µg (high dose) and 0.1 µg (low dose) of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety and efficacy trial consisted of three Stages: Stage A and B studies were an expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was then conducted in two parts (high dose and low dose), each enrolling 80 participants: 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients, 20 borderline tuberculoid/tuberculoid (BT/TT) leprosy patients, 20 household contacts of leprosy patients (HC), and 20 tuberculosis (TB) patients. The primary outcome measure for the skin test was delayed type hypersensitivity induration. Findings In the small Phase I safety trial, reactions were primarily against the 2.5 µg dose of both antigens and Rees control antigen, which were then excluded from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26% of subjects (13 of 50) showed induration against the high dose of each antigen, and 4% (2 of 50) reacted to the low dose of MLSA-LAM. Phase II, Stage C safety and initial efficacy trial showed that both antigens at the low dose exhibited low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at 100% and 95% compared to TB patients. The high dose of both antigens showed lower specificity (70% and 60%) and sensitivity (10% and 15%). BL/LL leprosy patients were anergic to the leprosy antigens. Interpretation MLSA-LAM and MLCwA at both high (1.0 µg) and low (0.1 µg) doses were found to be safe for use in humans without known exposure to leprosy and in target populations. At a sensitivity rate of 20–25% these antigens are not suitable as a skin test for the detection of the early stages of leprosy infection; however, the degree of specificity is impressive given the presence of cross-reactive antigens in these complex native M. leprae preparations. Trial Registration ClinicalTrails.gov NCT01920750 (Phase I), NCT00128193 (Phase II), Author Summary Clinically useful skin test reagents should be safe and sufficiently sensitive to detect infection prior to physical manifestations of leprosy disease. While in these small scale human studies, leprosy reagents were safe for use in humans, they failed in respect of sensitivity at a rate of 20–25% in the key indicator group, BT/TT leprosy patients. Specificity in terms of leprosy vs. tuberculosis at a rate of 95–100% was surprisingly high in light of the extensive presence of cross-reactive antigens in the complex native M. leprae preparations. These results could justify a further trial at lower dosages.

Mark Wolff is assistant professor of French at Hartwick College. His research interests include the nineteenth-century French novel, the sociology of literature, popular literature, and canon formation. He is also actively involved in humanities computing.

The authors conducted a 2-year, multicenter, double-blind, placebo-controlled efficacy field trial of live, attenuated, cold-adapted, trivalent influenza vaccine administered by nasal spray to children 15-71 months old. Overall, vaccine was 92% efficacious at preventing culture-confirmed infection by influenza A/H3N2 and influenza B. Because influenza A/H1N1 did not cause disease during the years in which this study was conducted, the authors sought to determine vaccine efficacy and correlates of immune protection against experimental challenge with 107 TCID50 of attenuated H1N1 (vaccine strain) by intranasal spray. Prechallenge assessments included serum hemaglutination-inhibiting (HAI) antibody and nasal wash IgA antibody to H1N1. Vaccine was 83% efficacious (95% confidence interval, 60%-93%) at preventing shedding of H1N1 virus after challenge. Any serum HAI antibody or any nasal wash IgA antibody was correlated with significant protection from H1N1 infection as indicated by vaccine-virus shedding, and high efficacy against H1N1 challenge was demonstrated.

The authors provide an analysis of data from a two-year (1996-1998), multicenter (ten US cities), double-blinded, placebo-controlled influenza vaccine trial in children. The vaccine was the trivalent cold-adapted influenza vaccine. Estimates are made of the vaccine efficacy for susceptibility to culture-confirmed influenza (VE(S)) while taking inter-center variability in the risk of infection into account. Our overall estimate of VE(S) against influenza is 0.92 (95% confidence interval (CI) 0.89-0.94). In addition, for the second year, although the vaccine contained antigen for A/Wuhan-like (H3N2), the estimated VE(S) for epidemic variant A/Sydney-like (H3N2) was 0.89 (95% CI 0.81-0.94). Thus, the vaccine showed a high degree of protection against a variant not closely matched to the vaccine antigen. With regard to natural immunity, an influenza A infection in the first year reduces the estimated risk of an influenza A infection in the second year by a factor of 0.88 (95% CI 0.21-0.98). When comparing year 1 to year 2, there is a negative correlation of -0.50 in the center-specific attack rates in the placebo groups. This is consistent with the theory that natural immunity provides overall community protection to children. The authors argue that mass vaccination of 70% of the children with the cold-adapted influenza vaccine could provide substantial protection to the community at large.