Development of a therapeutic vaccine for the treatment of cocaine addiction.

PubMed

Fox, B S

1997-12-15

No pharmacotherapies have yet been approved for the treatment of cocaine addiction. One new approach is to block the effects of cocaine with anti-cocaine antibodies induced by a therapeutic cocaine vaccine. A cocaine vaccine has been developed which induces a cocaine-specific antibody response in rodents. The antibody binds to cocaine in the circulation and can be shown to inhibit the ability of cocaine to enter the brain. Furthermore, anti-cocaine antibody can inhibit cocaine self-administration in rats. These data suggest that a cocaine vaccine may be a powerful therapeutic tool. The intent is to immunized motivated patients with the vaccine as part of a comprehensive treatment program. If the patient uses cocaine after being vaccinated, the antibody will inhibit the reinforcing activity of cocaine and decrease the likelihood of relapse.

[Maintenance treatment in opioid-dependent patients with migration background].

PubMed

Bald, L K; Schouler-Ocak, M; Penka, S; Schoofs, N; Häbel, T; Bermpohl, F; Gutwinski, S

2016-05-01

No regional analyses regarding opioid-dependent patients in maintenance treatment with a migration background have so far been performed in German-speaking countries. This study examined patients with and without a migration background regarding socioeconomic parameters, characteristics of dependency and attitude towards opiate maintenance treatment (OMT). From May to October 2011 patients in OMT from all of the 20 psychiatry clinics and 110 physician practices in Berlin with a licence to provide OMT were included in this analysis. Out of the 986 participating patients, 956 gave information on migration background and of these, 204 (21.3 %) originated from a country other than Germany. Compared to patients without a migration background, their participation in a maintenance program was significantly shorter and they more often expressed a desire to end OMT and wanted a limited duration of OMT. The differences regarding duration of OMT and the wish to end OMT can reflect a stronger desire for abstinence and a different attitude towards maintenance treatment of patients with a migration background.

Mandibular overdentures: a review of treatment philosophy and prosthodontic maintenance.

PubMed

Al-Zubeidi, Mohammed I; Payne, Alan G T

2007-12-01

Root overdentures and implant overdentures are two similar treatment options for the nearly-edentulous or edentulous mandible. The purpose of this literature review was to specifically compare their prosthodontic treatment philosophies and follow-up maintenance requirements. Critical comparison of these two prosthodontic treatment philosophies revealed that the foundation for overdentures which is provided by oral implants is more predictable than that provided by the roots of natural teeth. The two treatment modalities have both similarities and differences in their associated prosthodontic maintenance. The findings of this literature review suggest the future possibility that mandibular root overdentures may become obsolete as a treatment approach.

Whole Cell Therapeutic Vaccine Modified With Hyper-IL6 for Combinational Treatment of Nonresected Advanced Melanoma.

PubMed

Mackiewicz, Jacek; Karczewska-Dzionk, Aldona; Laciak, Maria; Kapcinska, Malgorzata; Wiznerowicz, Maciej; Burzykowski, Tomasz; Zakowska, Monika; Rose-John, Stefan; Mackiewicz, Andrzej

2015-05-01

Active specific immunotherapy of cancer requires an efficient induction and effector phase. The induction covers potent activation of anti-tumor response, whereas effector breaks the immunosuppression. We report efficacy of therapeutic melanoma vaccine (AGI-101H) used alone in advanced disease as a candidate for further combined treatment. In adjuvant setting in patients with resected metastases AGI-101H combined with surgery of recurring disease demonstrated long-term survival. Seventy-seven patients with nonresectable melanoma (8% IIIB, 21% IIIC, 71% IV) were enrolled. AGI-101H was administered 8× every 2 weeks, and then every month. At progression, maintenance was continued or induction was repeated and followed by maintenance. Median follow-up was 139.3 months. The median overall survival (OS) was 17.3 months; in patients with WHO 0-1 was 20.3 months. Complete response (CR) and partial response (PR) were observed in 19.4% and 9% of pts. Disease control rate was 54.5% of pts. The median CR+PR duration was 32 months. Reinduction was performed in 36.3% patients following disease progression with 46.6% of CR+PR. No grade 3/4 adverse events were observed. Treatment with AGI-101H of melanoma patients is safe and effective. AGI-101H is a good candidate for combinatorial treatment with immune check-points inhibitors or tumor hypoxia normalizators. EudraCT Number 2008-003373-40.

Informed consent to opioid agonist maintenance treatment: recommended ethical guidelines.

PubMed

Carter, Adrian; Hall, Wayne

2008-02-01

Some bioethicists have questioned whether opioid addicted individuals are able to provide free and informed consent to opioid agonist maintenance treatment. Conflicting motives for providing such treatment (e.g. improving the personal health of addicts and protecting public health and order) can also influence what individuals are required to consent to, and how that consent is obtained. We discuss both issues and attempt to specify the conditions for obtaining informed consent to agonist maintenance treatment for opioid addiction. We briefly review the neuroscientific literature on the effects of addiction on the autonomy and decision-making capacity of opioid dependent individuals, and ascertain how informed consent to the treatment of opioid addiction should be obtained. We also provide an ethical analysis of the competing social and medical forces that influence the consent process and make some recommendations on how to ensure that individuals enter maintenance treatment that is provided in an effective and ethical way. Our analysis shows that whilst the autonomy of opioid dependent individuals is impaired by their addiction, they do retain the ability to consent to treatment provided they are not in acute withdrawal or intoxication. These symptoms should have abated, either by supervised withdrawal or stabilisation on agonist maintenance, before they are asked to consent to a detailed treatment contract. Once stabilised, individuals should be provided with detailed information about the risks and benefits of all treatments, and restrictions and regulations under which they are provided. Informed consent is an important part of the treatment process that should be obtained in ways that increase the autonomy and decision-making capacity in opioid addicts.

Methadone maintenance treatment (MMT): a review of historical and clinical issues.

PubMed

Joseph, H; Stancliff, S; Langrod, J

2000-01-01

Methadone maintenance has been evaluated since its development in 1964 as a medical response to the post-World War II heroin epidemic in New York City. The findings of major early studies have been consistent. Methadone maintenance reduces and/or eliminates the use of heroin, reduces the death rates and criminality associated with heroin use, and allows patients to improve their health and social productivity. In addition, enrollment in methadone maintenance has the potential toreduce the transmission of infectious diseases associated with heroin injection, such as hepatitis and HIV. The principal effects of methadone maintenance are to relieve narcotic craving, suppress the abstinence syndrome, and block the euphoric effects associated with heroin. A majority of patients require 80-120 mg/d of methadone, or more, to achieve these effects and require treatment for an indefinite period of time, since methadone maintenance is a corrective but not a curative treatment for heroin addiction. Lower doses may not be as effective or provide the blockade effect. Methadone maintenance has been found to be medically safe and nonsedating. It is also indicated for pregnant women addicted to heroin. Reviews issued by the Institute of Medicine and the National Institutes of Health have defined narcotic addiction as a chronic medical disorder and have claimed that methadone maintenance coupled with social services is the most effective treatment for this condition. These agencies recommend reducing governmental regulation to facilitate patients access to treatment. In addition, they recommend that the number of programs be expanded, and that new models of treatment be implemented,if the nationwide problem of addiction is to be brought under control. The National Institutes of Health also recommend that methadone maintenance be available to persons under legal supervision, such as probationers, parolees and the incarcerated. However, stigma and bias directed at the programs and the

Waning of vaccine-induced immunity to measles in kidney transplanted children.

PubMed

Rocca, Salvatore; Santilli, Veronica; Cotugno, Nicola; Concato, Carlo; Manno, Emma Concetta; Nocentini, Giulia; Macchiarulo, Giulia; Cancrini, Caterina; Finocchi, Andrea; Guzzo, Isabella; Dello Strologo, Luca; Palma, Paolo

2016-09-01

Vaccine-preventable diseases are a significant cause of morbidity and mortality in solid organ transplant recipients who undergo immunosuppression after transplantation. Data on immune responses and long-term maintenance after vaccinations in such population are still limited.We cross-sectionally evaluated the maintenance of immune response to measles vaccine in kidney transplanted children on immunosuppressive therapy. Measles-specific enzyme-linked immunosorbent assay and B-cell enzyme-linked immunosorbent spot were performed in 74 kidney transplant patients (Tps) and in 23 healthy controls (HCs) previously vaccinated and tested for humoral protection against measles. The quality of measles antibody response was measured by avidity test. B-cell phenotype, investigated via flow cytometry, was further correlated to the ability of Tps to maintain protective humoral responses to measles over time.We observed the loss of vaccine-induced immunity against measles in 19% of Tps. Nonseroprotected children showed signs of impaired B-cell distribution as well as immune senescence and lower antibody avidity. We further reported as time elapsed between vaccination and transplantation, as well as the vaccine administration during dialysis are clinical factors affecting the maintenance of the immune memory response against measles.Tps present both quantitative and qualitative alterations in the maintenance of protective immunity to measles vaccine. Prospective studies are needed to optimize the vaccination schedules in kidney transplant recipients in order to increase the immunization coverage over time in this population.

Oxcarbazepine in the maintenance treatment of bipolar disorder.

PubMed

Vasudev, A; Macritchie, K; Watson, S; Geddes, J R; Young, A H

2008-01-23

Some studies have suggested that oxcarbazepine has a role in preventing episode recurrence in bipolar affective disorder. This review attempted to investigate the existing evidence from randomised controlled trials for its use in the maintenance treatment of this illness. To review the efficacy of oxcarbazepine, relative to placebo and other agents, in the prevention of affective episodes of bipolar affective disorder. The efficacy of oxcarbazepine was considered in terms of episode recurrence, general and social functioning. Adverse effects, overall acceptability to participants and mortality were also considered. CCDANCTR-Studies and CCDANCTR-References were searched on 7/11/2007. Medline, CENTRAL, EMBASE and PsycINFO were searched in March 2007. Specialist journals and conference proceedings were handsearched. Reference lists of relevant papers and major textbooks of affective disorder were checked. Authors, experts in the field and pharmaceutical companies were contacted requesting information on published or unpublished trials. Randomised controlled trials comparing oxcarbazepine with placebo or alternative agents, where the stated intent of intervention was the maintenance treatment of bipolar affective disorder were sought. Participants with bipolar disorder, male and female, of all ages, were included. Data were extracted from the original reports individually by two review authors. The methodological quality of included studies was assessed individually by two review authors. The main outcomes were the efficacy of oxcarbazepine maintenance treatment in preventing or attenuating further episodes of bipolar affective disorder (including its efficacy in rapid cycling disorder), the acceptability of oxcarbazepine treatment to participants, the prevalence of side-effects, and mortality, if any, on oxcarbazepine treatment. Where appropriate, data concerning outcome measures and adverse effects were to be extracted from the studies and analysed using Review

Successful treatment of chronic hepatitis C with pegylated interferon in combination with ribavirin in a methadone maintenance treatment program

PubMed Central

Litwin, Alain H.; Harris, Kenneth A.; Nahvi, Shadi; Zamor, Philippe J.; Soloway, Irene J.; Tenore, Peter L.; Kaswan, Daniel; Gourevitch, Marc. N.; Arnsten, Julia H.

2009-01-01

Injection drug users constitute 60% of the more than 4 million people in the United States with hepatitis C virus (HCV), including many methadone maintenance patients. Few data exist describing clinical outcomes for patients receiving HCV treatment on-site in a methadone maintenance settings. In this retrospective study, we describe clinical outcomes for 73 patients receiving HCV treatment on-site in a methadone maintenance treatment program. Fifty-five percent of patients achieved end-of-treatment response, and 45% achieved sustained viral response. These treatment response rates are nearly equivalent to previously published HCV treatment response rates, despite high prevalences of ongoing drug use (49%), psychiatric comorbidity (67%), and HIV coinfection (32%). These data show that on-site HCV treatment with pegylated interferon and ribavirin is effective in methadone-maintained patients, many of whom are active drug users, psychiatrically ill, or HIV coinfected, and that methadone maintenance treatment programs represent an opportunity to safely treat chronic hepatitis C. PMID:19038524

Anthrax prevention and treatment: utility of therapy combining antibiotic plus vaccine.

PubMed

Klinman, Dennis M; Yamamoto, Masaki; Tross, Debra; Tomaru, Koji

2009-12-01

The intentional release of anthrax spores in 2001 confirmed this pathogen's ability to cause widespread panic, morbidity and mortality. While individuals exposed to anthrax can be successfully treated with antibiotics, pre-exposure vaccination can reduce susceptibility to infection-induced illness. Concern over the safety and immunogenicity of the licensed US vaccine (Anthrax Vaccine Adsorbed (AVA)) has fueled research into alternatives. Second-generation anthrax vaccines based on purified recombinant protective antigen (rPA) have entered clinical trials. These rPA vaccines induce neutralizing antibodies that prevent illness, but the magnitude and duration of the resultant protective response is modest. Efforts are underway to bolster the immunogenicity of rPA by combining it with adjuvants and other immunostimulatory agents. Third generation vaccines are under development that utilize a wide variety of immunization platforms, antigens, adjuvants, delivery methods and routes of delivery to optimize the induction of a protective immunity. For the foreseeable future, vaccination will rely on first and second generation vaccines co-administered with immune adjuvants. Optimal post-exposure treatment of immunologically naive individuals should include a combination of vaccine plus antibiotic therapy.

Aripiprazole for the maintenance treatment of bipolar I disorder: A review.

PubMed

McIntyre, Roger S

2010-01-01

Bipolar disorder is a chronic neuropsychiatric syndrome associated with substantial rates of recurrence, interepisodic dysfunction, comorbidity, and premature mortality. Metabolic comorbidity (eg, overweight, obesity, metabolic syndrome) differentially affects individuals with bipolar disorder and contributes to increased illness-associated morbidity and mortality (ie, cardiovascular disease). Few pharmacologic agents have been approved by the US Food and Drug Administration for the maintenance treatment of bipolar disorder. This paper discusses the metabolic profile of aripiprazole and reviews pivotal registration trials of aripiprazole for the maintenance treatment of adults with bipolar I disorder. MEDLINE was searched for English-language articles published between January 1995 and November 2009. The key search term was aripiprazole, combined with bipolar disorder and maintenance treatment. The review was limited to randomized, controlled registration trials, supplemented by poster presentations involving the registration-trial data sets. Three studies of the efficacy and tolerability of aripiprazole monotherapy in the maintenance treatment of bipolar I disorder were identified by the literature search: a 26-week, randomized, double-blind study and its 74-week extension phase (for a total of 100 weeks of double-blind treatment), and a randomized, double-blind comparison of aripiprazole with placebo and lithium (internal comparator) for up to 12 weeks. After 100 weeks of double-blind treatment, aripiprazole had a minimal effect on body composition and did not disrupt metabolic parameters compared with placebo. The mean (SD) weight change was 0.4 (0.8) kg with aripiprazole and -1.9 (0.8) kg with placebo (P = NS). A clinically significant (> or =7%) increase in weight occurred in 20% of the aripiprazole group and 5% of the placebo group (P = 0.01). Extrapyramidal symptoms were reported in 22% of the aripiprazole group and 15% of the placebo group. The identified

Chemical-free inactivated whole influenza virus vaccine prepared by ultrashort pulsed laser treatment

NASA Astrophysics Data System (ADS)

Tsen, Shaw-Wei David; Donthi, Nisha; La, Victor; Hsieh, Wen-Han; Li, Yen-Der; Knoff, Jayne; Chen, Alexander; Wu, Tzyy-Choou; Hung, Chien-Fu; Achilefu, Samuel; Tsen, Kong-Thon

2015-05-01

There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques.

DEVELOPING A VACCINE AGAINST MULTIPLE PSYCHOACTIVE TARGETS: A CASE STUDY OF HEROIN

PubMed Central

Stowe, G. Neil; Schlosburg, Joel E.; Vendruscolo, Leandro F.; Edwards, Scott; Misra, Kaushik K.; Schulteis, Gery; Zakhari, Joseph S.; Koob, George F.; Janda, Kim D.

2012-01-01

Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. Currently approved heroin addiction medications include drugs that bind at the same receptors (e.g. opioid receptors) occupied by heroin and/or its metabolites in the brain, but undesired side effects of these treatments, maintenance dependence and relapse to drug taking remains problematic. A vaccine capable of blocking heroin’s effects could provide an economical, long-lasting and sustainable adjunct to heroin addiction therapy without the side effects associated with available treatment options. Heroin, however, presents a particularly challenging vaccine target as it is metabolized to multiple psychoactive molecules of differing lipophilicity, with differing abilities to cross the blood brain barrier. In this review, we discuss the opiate scaffolding and hapten design considerations to confer immunogenicity as well as the specificity of the immune response towards structurally similar opiates. In addition, we detail different strategies employed in the design of immunoconjugates for a vaccine-based therapy for heroin addiction treatment. PMID:22229311

Decline in in-patient treatments of genital warts among young Australians following the national HPV vaccination program.

PubMed

Ali, Hammad; Guy, Rebecca J; Wand, Handan; Read, Tim Rh; Regan, David G; Grulich, Andrew E; Fairley, Christopher K; Donovan, Basil

2013-03-18

There has been a rapid decline in the number of young heterosexuals diagnosed with genital warts at outpatient sexual health services since the national human papillomavirus (HPV) vaccination program started in Australia in 2007. We assessed the impact of the vaccination program on the number of in-patient treatments for genital warts. Data on in-patient treatments of genital warts in all private hospitals were extracted from the Medicare website. Medicare is the universal health insurance scheme of Australia. In the vaccine period (2007-2011) and pre-vaccine period (2000-2007) we calculated the percentage change in treatment numbers and trends in annual treatment rates in private hospitals. Australian population data were used to calculate rates. Summary rate ratios of average annual trends were determined. Between 2000 and 2011, 6,014 women and 936 men aged 15-44 years underwent in-patient treatment for genital warts in private hospitals. In 15-24 year old women, there was a significant decreasing trend in annual treatment rates of vulval/vaginal warts in the vaccine period (overall decrease of 85.3% in treatment numbers from 2007 to 2011) compared to no significant trend in the pre-vaccine period (summary rate ratio (SRR) = 0.33, p < 0.001). In 25-34 year old women, declining trends were seen in both vaccine and pre-vaccine periods (overall decrease of 33% vs. 24.3%), but the rate of change was greater in the vaccine period (SRR = 0.60, p < 0.001). In 35-44 year old women, there was no significant change in both periods (SRR = 0.91, p = 0.14). In 15-24 year old men, there was a significant decreasing trend in annual treatment rates of penile warts in the vaccine period (decrease of 70.6%) compared to an increasing trend in the pre-vaccine period (SRR = 0.76, p = 0.02). In 25-34 year old men there was a significant decreasing trend in the vaccine period compared to no change in the pre-vaccine period (SRR = 0.81, p = 0

Vaccination versus treatment of influenza in working adults: a cost-effectiveness analysis.

PubMed

Rothberg, Michael B; Rose, David N

2005-01-01

To determine the cost-effectiveness of influenza vaccination, antiviral therapy, or no intervention for healthy working adults, accounting for annual variation in vaccine efficacy. We conducted a cost-effectiveness analysis based on published clinical trials of influenza vaccine and antiviral drugs, incorporating 10 years of surveillance data from the World Health Organization. We modeled influenza vaccination, treatment of influenza-like illness with antiviral drugs, or both, as compared with no intervention, targeting healthy working adults under age 50 years in the general community or workplace. Outcomes included costs, illness days, and quality-adjusted days gained. In the base case analysis, the majority of costs incurred for all strategies were related to lost productivity from influenza illness. The least expensive strategy varied from year to year. For the 10-year period, antiviral therapy without vaccination was associated with the lowest overall costs (234 US dollars per person per year). Annual vaccination cost was 239 US dollars per person, and was associated with 0.0409 quality-adjusted days saved, for a marginal cost-effectiveness ratio of 113 US dollars per quality-adjusted day gained or 41,000 US dollars per quality-adjusted life-year saved compared with antiviral therapy. No intervention was the most expensive and least effective option. In sensitivity analyses, lower vaccination costs, higher annual probabilities of influenza, and higher numbers of workdays lost to influenza made vaccination more cost-effective than treatment. If vaccination cost was less than 16 US dollars or time lost from work exceeded 2.4 days per episode of influenza, then vaccination was cost saving compared with all other strategies. Influenza vaccination for healthy working adults is reasonable economically, and under certain circumstances is cost saving. Antiviral therapy is consistently cost saving.

[Therapeutic bacterial vaccine Immunovac in complex treatment of patients with chronic pyoderma].

PubMed

Sorokina, E V; Masiukova, S A; Kurbatova, E A; Egorova, N B

2010-01-01

Assessment of therapeutic effect and immunologic parameters during use of Immunovac vaccine for complex treatment of chronic forms of pyoderma. Ninety-five patients with different clinical forms of chronic pyoderma (furunculosis, hydradenitis, chronic ulcerative and ulcerative-vegetans pyoderma, folliculitis, impetigo etc.) were studied. Fifty-nine patients received immunotherapy with Immunovac vaccine together with basic therapy and 36 patients comprised control group treated only with basic therapy. Studied immunologic parameters were as follows: assessment of functional activity of lymphocytes, determination of lymphocyte subpopulations by flow cytometry, total immunoglobulins classes A, G, M by radial immunoduffusion, affinity of antibodies by enzyme immunoassay, levels of IFNalpha and IFNgamma. Use of Immunovac vaccine in complex treatment of patients with chronic forms of pyoderma enhanced clinical effect of basic therapy, which expressed in decrease of severity and frequency of disease relapses irrespective to clinical form and severity of pyoderma. Therapeutic effect during use of Immunovac vaccine amounted 84.7%, whereas in control group it was 41.6% after 12 months of follow-up. Increase of functional activity of neutrophils, subpopulation of lymphocytes with markers CD4+, CD8+, CD72+, affinity of antibodies as well as induced production of IFNalpha and IFNgamma was revealed. Correction of immunologic parameters correlated with positive results of patients treatment. Inclusion of bacterial polycomponent vaccine Immunovac in complex treatment of patients with chronic pyoderma promotes enhancement of therapeutic effect of basic therapy and correction of immunologic parameters.

DC vaccination with anti-CD25 treatment leads to long-term immunity against experimental glioma

PubMed Central

Maes, Wim; Rosas, Georgina Galicia; Verbinnen, Bert; Boon, Louis; De Vleeschouwer, Steven; Ceuppens, Jan L.; Van Gool, Stefaan W.

2009-01-01

We studied the feasibility, efficacy, and mechanisms of dendritic cell (DC) immunotherapy against murine malignant glioma in the experimental GL261 intracranial (IC) tumor model. When administered prophylactically, mature DCs (DCm) ex vivo loaded with GL261 RNA (DCm-GL261-RNA) protected half of the vaccinated mice against IC glioma, whereas treatment with mock-loaded DCm or DCm loaded with irrelevant antigens did not result in tumor protection. In DCm-GL261-RNA–vaccinated mice, a tumor-specific cellular immune response was observed ex vivo in the spleen and tumor-draining lymph node cells. Specificity was also shown in vivo on the level of tumor challenge. Depletion of CD8+ T-cells by anti-CD8 treatment at the time of tumor challenge demonstrated their essential role in vaccine- mediated antitumor immunity. Depletion of CD25+ regulatory T-cells (Tregs) by anti-CD25 (aCD25) treatment strongly enhanced the efficacy of DC vaccination and was itself also protective, independently of DC vaccination. However, DC vaccination was essential to protect the animals from IC tumor rechallenge. No long-term protection was observed in animals that initially received aCD25 treatment only. In mice that received DC and/or aCD25 treatment, we retrieved tumor-specific brain-infiltrating cytotoxic T-lymphocytes. These data clearly demonstrate the effectiveness of DC vaccination for the induction of long-lasting immunological protection against IC glioma. They also show the beneficial effect of Treg depletion in this kind of glioma immunotherapy, even combined with DC vaccination. PMID:19336528

Patterns of acquisitive crime during methadone maintenance treatment among patients eligible for heroin assisted treatment.

PubMed

van der Zanden, Bart P; Dijkgraaf, Marcel G W; Blanken, Peter; van Ree, Jan M; van den Brink, Wim

2007-01-05

To determine the patterns of acquisitive crime during methadone maintenance treatment among chronic, treatment-resistant heroin users eligible for heroin assisted treatment in the Netherlands. We retrospectively assessed the type and number of illegal activities during 1 month of standard methadone maintenance treatment in 51 patients prior to the start of heroin assisted treatment. Data were collected using a semi-structured interview focussed on crime with special emphasis on property crime. Volume analyses consisted of frequencies and descriptives of mean numbers of offences per day and per type. In a Dutch population of problematic drug users eligible for and prior to commencing heroin assisted treatment, 70% reported criminal activities and 50% reported acquisitive crimes. Offending took place on 20.5 days per month with on average 3.1 offences a day. Acquisitive crime consisted mainly of shoplifting (mean 12.8 days, 2.2 times/day) and theft of bicycles (mean 5.8 days, 2.4 times/day); theft from a vehicle and burglaries were committed less frequently. The majority of these patients (63%) reported to have started offending in order to acquire illicit drugs and alcohol. During methadone maintenance treatment, 50% of criminally active, problematic heroin users eligible for heroin assisted treatment reported acquisitive crime. Shoplifting, thefts and/or other property crimes were committed on average two to three times on a crime day. This study discusses that the detail provided by self-reported crime data can improve cost estimates in economic evaluations of heroin assisted treatment.

Phenolized vaccine treatment of people exposed to rabies in southern India

PubMed Central

Veeraraghavan, N.

1954-01-01

The records of antirabies treatment given under the auspices of the Pasteur Institute of Southern India, Coonoor, to 412,800 persons between 1907 and 1951 are analysed. The results of treatment with dried-cord, Högyes, and 1%, 2%, and 5% Semple vaccines are assessed, taking into consideration the various factors in their preparation. An account is given of an enquiry which has been in progress since 1946 into comparative mortality among untreated bitten persons and those treated with 5% Semple vaccine. PMID:13182601

Decline in in-patient treatments of genital warts among young Australians following the national HPV vaccination program

PubMed Central

2013-01-01

Background There has been a rapid decline in the number of young heterosexuals diagnosed with genital warts at outpatient sexual health services since the national human papillomavirus (HPV) vaccination program started in Australia in 2007. We assessed the impact of the vaccination program on the number of in-patient treatments for genital warts. Methods Data on in-patient treatments of genital warts in all private hospitals were extracted from the Medicare website. Medicare is the universal health insurance scheme of Australia. In the vaccine period (2007–2011) and pre-vaccine period (2000–2007) we calculated the percentage change in treatment numbers and trends in annual treatment rates in private hospitals. Australian population data were used to calculate rates. Summary rate ratios of average annual trends were determined. Results Between 2000 and 2011, 6,014 women and 936 men aged 15–44 years underwent in-patient treatment for genital warts in private hospitals. In 15–24 year old women, there was a significant decreasing trend in annual treatment rates of vulval/vaginal warts in the vaccine period (overall decrease of 85.3% in treatment numbers from 2007 to 2011) compared to no significant trend in the pre-vaccine period (summary rate ratio (SRR) = 0.33, p < 0.001). In 25–34 year old women, declining trends were seen in both vaccine and pre-vaccine periods (overall decrease of 33% vs. 24.3%), but the rate of change was greater in the vaccine period (SRR = 0.60, p < 0.001). In 35–44 year old women, there was no significant change in both periods (SRR = 0.91, p = 0.14). In 15–24 year old men, there was a significant decreasing trend in annual treatment rates of penile warts in the vaccine period (decrease of 70.6%) compared to an increasing trend in the pre-vaccine period (SRR = 0.76, p = 0.02). In 25–34 year old men there was a significant decreasing trend in the vaccine period compared to no change in

Hospitalized patients with COPD: analysis of prior treatment*

PubMed Central

Giacomelli, Irai Luis; Steidle, Leila John Marques; Moreira, Frederico Fernandes; Meyer, Igor Varela; Souza, Ricardo Goetten; Pincelli, Mariângela Pimentel

2014-01-01

Objective: Although COPD is a prevalent disease, it is undertreated, and there are no available data regarding previous treatment of COPD in Brazil. This study aimed to determine the appropriateness of maintenance treatment in COPD patients prior to their hospitalization and to identify variables associated with inappropriate treatment. Methods: This was an observational, cross-sectional, analytical study involving 50 inpatients with COPD at two hospitals in the city of Florianópolis, Brazil. The patients completed a questionnaire on parameters related to the maintenance treatment of COPD. Non-pharmacological management and pharmacological treatment were assessed based on the recommendations made by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2011 and by the Brazilian National Ministry of Health in the chronic respiratory diseases section of its Caderno de Atenção Básica (CAB, Primary Care Guidebook). Results: In most of the patients, the COPD was classified as being severe or very severe. Regarding non-pharmacological management, 33% of the patients were smokers, only 32% had been advised to receive the flu vaccine, 28% had received pneumococcal vaccine, and only 6.5% of the patients in the B, C, and D categories received pulmonary rehabilitation. Regarding GOLD and CAB recommendations, pharmacological treatment was inappropriate in 50% and 74% of the patients, respectively. Based on GOLD recommendations, 38% were undertreated. A low level of education, low income, not receiving oxygen therapy, and not receiving the flu vaccine were associated with inappropriate treatment. Conclusions: The application of various non-pharmacological management recommendations was unsatisfactory. Regarding the GOLD recommendations, the high rate of inappropriate maintenance treatment was mainly due to undertreatment. In Brazil, even in severe COPD cases, optimizing treatment to achieve greater benefits continues to be a challenge. PMID:25029645

Impact of treatment reduction for childhood acute lymphoblastic leukemia on serum immunoglobulins and antibodies against vaccine-preventable diseases.

PubMed

van Tilburg, Cornelis M; Bierings, Marc B; Berbers, Guy A M; Wolfs, Tom F W; Pieters, Rob; Bloem, Andries C; Sanders, Elisabeth A M

2012-05-01

The consequences of current intensive chemotherapy for childhood acute lymphoblastic leukemia (ALL) for immune defense are a matter of concern. The purpose of this study was to examine the effect of reduced compared with intensive (conventional) ALL chemotherapy on serum immunoglobulin levels and specific antibody concentrations against vaccine-preventable diseases. Patients treated according to Dutch Childhood Oncology Group ALL 10 protocol were stratified by minimal residual disease to receive reduced (standard risk; SR) or intensive (medium risk; MR) intensification/maintenance treatment. Between November 2004 and July 2009 we compared serum immunoglobulins of 110 patients and specific antibodies against diphtheria toxin, tetanus toxin, and Bordetella pertussis antigens of 41 patients of SR and MR groups during chemotherapy. Immunoglobulin levels showed significantly different patterns between the SR and MR groups. In the MR group IgG, IgA, and IgM levels decreased towards the end of intensive treatment; in the SR group IgG levels increased while IgA and IgM stabilized. In both groups IgM and IgG levels were most affected. Specific antibody levels against vaccine-preventable diseases decreased in both groups, but more profound in MR group. Although reduced chemotherapy is beneficial for immunoglobulin level recovery and might prevent susceptibility for infections, specific antibodies remain decreased. Copyright © 2011 Wiley Periodicals, Inc.

Social Justice and HIV Vaccine Research in the Age of Pre-Exposure Prophylaxis and Treatment as Prevention

PubMed Central

Bailey, Theodore C.; Sugarman, Jeremy

2014-01-01

The advent of pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) as means of HIV prevention raises issues of justice concerning how most fairly and equitably to apportion resources in support of the burgeoning variety of established HIV treatment and prevention measures and further HIV research, including HIV vaccine research. We apply contemporary approaches to social justice to assess the ethical justification for allocating resources in support of HIV vaccine research given competing priorities to support broad implementation of HIV treatment and prevention measures, including TasP and PrEP. We argue that there is prima facie reason to believe that a safe and effective preventive HIV vaccine would offer a distinct set of ethically significant benefits not provided by current HIV treatment or prevention methods. It is thereby possible to justify continued support for HIV vaccine research despite tension with priorities for treatment, prevention, and other research. We then consider a counter-argument to such a justification based on the uncertainty of successfully developing a safe and effective preventive HIV vaccine. Finally, we discuss how HIV vaccine research might now be ethically designed and conducted given the new preventive options of TasP and PrEP, focusing on the ethically appropriate standard of prevention for HIV vaccine trials. PMID:24033297

Ethical Implications in Vaccine Pharmacotherapy for Treatment and Prevention of Drug of Abuse Dependence.

PubMed

Carfora, Anna; Cassandro, Paola; Feola, Alessandro; La Sala, Francesco; Petrella, Raffaella; Borriello, Renata

2018-03-01

Different immunotherapeutic approaches are in the pipeline for the treatment of drug dependence. "Drug vaccines" aim to induce the immune system to produce antibodies that bind to drugs and prevent them from inducing rewarding effects in the brain. Drugs of abuse currently being tested using these new approaches are opioids, nicotine, cocaine, and methamphetamine. In human clinical trials, "cocaine and nicotine vaccines" have been shown to induce sufficient antibody levels while producing few side effects. Studies in humans, determining how these vaccines interact in combination with their target drug, are underway. However, although vaccines can become a reasonable treatment option for drugs of abuse, there are several disadvantages that must be considered. These include i) great individual variability in the formation of antibodies, ii) the lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice, and iii) the lack of an effect on the drug desire that may predispose an addict to relapse. In addition, a comprehensive overview of several crucial ethical issues has not yet been widely discussed in order to have not only a biological approach to immunotherapy of addiction. Overall, immunotherapy offers a range of possible treatment options: the pharmacological treatment of addiction, the treatment of overdoses, the prevention of toxicity to the brain or the heart, and the protection of the fetus during pregnancy. So far, the results obtained from a small-scale experiment using vaccines against cocaine and nicotine suggest that a number of important technical challenges still need to be overcome before such vaccines can be approved for clinical use.

Correlation between measles vaccine doses: implications for the maintenance of elimination.

PubMed

McKee, A; Ferrari, M J; Shea, K

2018-03-01

Measles eradication efforts have been successful at achieving elimination in many countries worldwide. Such countries actively work to maintain this elimination by continuing to improve coverage of two routine doses of measles vaccine following measles elimination. While improving measles vaccine coverage is always beneficial, we show, using a steady-state analysis of a dynamical model, that the correlation between populations receiving the first and second routine dose also has a significant impact on the population immunity achieved by a specified combination of first and second dose coverage. If the second dose is administered to people independently of whether they had the first dose, high second-dose coverage improves the proportion of the population receiving at least one dose, and will have a large effect on population immunity. If the second dose is administered only to people who have had the first dose, high second-dose coverage reduces the rate of primary vaccine failure, but does not reach people who missed the first dose; this will therefore have a relatively small effect on population immunity. When doses are administered dependently, and assuming the first dose has higher coverage, increasing the coverage of the first dose has a larger impact on population immunity than does increasing the coverage of the second. Correlation between vaccine doses has a significant impact on the level of population immunity maintained by current vaccination coverage, potentially outweighing the effects of age structure and, in some cases, recent improvements in vaccine coverage. It is therefore important to understand the correlation between vaccine doses as such correlation may have a large impact on the effectiveness of measles vaccination strategies.

Potential Vaccines and Post-Exposure Treatments for Filovirus Infections

PubMed Central

Friedrich, Brian M.; Trefry, John C.; Biggins, Julia E.; Hensley, Lisa E.; Honko, Anna N.; Smith, Darci R.; Olinger, Gene G.

2012-01-01

Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed. PMID:23170176

Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection.

PubMed

Stittelaar, Koert J; Neyts, Johan; Naesens, Lieve; van Amerongen, Geert; van Lavieren, Rob F; Holý, Antonin; De Clercq, Erik; Niesters, Hubert G M; Fries, Edwin; Maas, Chantal; Mulder, Paul G H; van der Zeijst, Ben A M; Osterhaus, Albert D M E

2006-02-09

There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. Here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called HPMPC or Vistide) or with a related acyclic nucleoside phosphonate analogue (HPMPO-DAPy) after lethal intratracheal infection of cynomolgus monkeys (Macaca fascicularis) with monkeypox virus (MPXV). MPXV causes a disease similar to human smallpox and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines. We show that initiation of antiviral treatment 24 h after lethal intratracheal MPXV infection, using either of the antiviral agents and applying various systemic treatment regimens, resulted in significantly reduced mortality and reduced numbers of cutaneous monkeypox lesions. In contrast, when monkeys were vaccinated 24 h after MPXV infection, using a standard human dose of a currently recommended smallpox vaccine (Elstree-RIVM), no significant reduction in mortality was observed. When antiviral therapy was terminated 13 days after infection, all surviving animals had virus-specific serum antibodies and antiviral T lymphocytes. These data show that adequate preparedness for a biological threat involving smallpox should include the possibility of treating exposed individuals with antiviral compounds such as cidofovir or other selective anti-poxvirus drugs.

Using YouTube to Disseminate Effective Vaccination Pain Treatment for Babies.

PubMed

Harrison, Denise; Wilding, Jodi; Bowman, Amanda; Fuller, Ann; Nicholls, Stuart G; Pound, Catherine M; Reszel, Jessica; Sampson, Margaret

2016-01-01

Infant vaccinations are necessary for public health, but are painful, causing distress to the infant and caregivers. Breastfeeding and sucrose effectively reduce infants' pain during vaccinations, and these strategies are recommended in health care provider (HCP)-targeted education and vaccination pain guidelines. However studies show these strategies are infrequently used. YouTube is a popular medium to publicly share and watch videos, and many consumer posted YouTube videos show distressed infants being vaccinated with no pain treatment. The aims of this study were to evaluate the reach and impact of a consumer-targeted YouTube video demonstrating use of effective pain reduction strategies during infant vaccinations. A brief consumer-targeted video showing two infants being vaccinated was posted onto YouTube on October 2013. One infant was breastfed and another infant received sucrose by mouth before and during the injection. A link to a viewer survey was visible on a banner near the end of the video. An intensive strategically planned knowledge dissemination strategy using the media, social media and messages to professional organizations took place to promote the video. Data analysis of the viewer survey, YouTube analytics of the reach of the video in terms of number of views, country of viewers, and comments relating to the video took place 12 months after the video was posted. Twelve months after posting, the video had 65,478views, 68 comments, 245 likes, 17 dislikes, and 90 shares. Average duration of viewer time was 65% of the video. The viewer survey was completed by 156 (0.24%) viewers; 90 (58%) answered as HCPs and 66 (42%) as parents. Survey results showed that the video was persuasive; intent to use or support breastfeeding or sucrose was high in both parents and HCPs after viewing the video. Comments posted were often emotional in nature, and were related to anti-vaccination (n = 26, 38%); effectiveness or positive personal experiences (n = 21, 32

Using YouTube to Disseminate Effective Vaccination Pain Treatment for Babies

PubMed Central

Harrison, Denise; Wilding, Jodi; Bowman, Amanda; Fuller, Ann; Nicholls, Stuart G.; Pound, Catherine M.; Reszel, Jessica; Sampson, Margaret

2016-01-01

Background Infant vaccinations are necessary for public health, but are painful, causing distress to the infant and caregivers. Breastfeeding and sucrose effectively reduce infants’ pain during vaccinations, and these strategies are recommended in health care provider (HCP)-targeted education and vaccination pain guidelines. However studies show these strategies are infrequently used. YouTube is a popular medium to publicly share and watch videos, and many consumer posted YouTube videos show distressed infants being vaccinated with no pain treatment. The aims of this study were to evaluate the reach and impact of a consumer-targeted YouTube video demonstrating use of effective pain reduction strategies during infant vaccinations. Methods A brief consumer-targeted video showing two infants being vaccinated was posted onto YouTube on October 2013. One infant was breastfed and another infant received sucrose by mouth before and during the injection. A link to a viewer survey was visible on a banner near the end of the video. An intensive strategically planned knowledge dissemination strategy using the media, social media and messages to professional organizations took place to promote the video. Data analysis of the viewer survey, YouTube analytics of the reach of the video in terms of number of views, country of viewers, and comments relating to the video took place 12 months after the video was posted. Results Twelve months after posting, the video had 65,478views, 68 comments, 245 likes, 17 dislikes, and 90 shares. Average duration of viewer time was 65% of the video. The viewer survey was completed by 156 (0.24%) viewers; 90 (58%) answered as HCPs and 66 (42%) as parents. Survey results showed that the video was persuasive; intent to use or support breastfeeding or sucrose was high in both parents and HCPs after viewing the video. Comments posted were often emotional in nature, and were related to anti-vaccination (n = 26, 38%); effectiveness or positive

The development of global vaccine stockpiles

PubMed Central

Yen, Catherine; Hyde, Terri B; Costa, Alejandro J; Fernandez, Katya; Tam, John S; Hugonnet, Stéphane; Huvos, Anne M; Duclos, Philippe; Dietz, Vance J; Burkholder, Brenton T

2016-01-01

Global vaccine stockpiles, in which vaccines are reserved for use when needed for emergencies or supply shortages, have effectively provided countries with the capacity for rapid response to emergency situations, such as outbreaks of yellow fever and meningococcal meningitis. The high cost and insufficient supply of many vaccines, including oral cholera vaccine and pandemic influenza vaccine, have prompted discussion on expansion of the use of vaccine stockpiles to address a wider range of emerging and re-emerging diseases. However, the decision to establish and maintain a vaccine stockpile is complex and must take account of disease and vaccine characteristics, stockpile management, funding, and ethical concerns, such as equity. Past experience with global vaccine stockpiles provide valuable information about the processes for their establishment and maintenance. In this Review we explored existing literature and stockpile data to discuss the lessons learned and to inform the development of future vaccine stockpiles. PMID:25661473

Cost utility of maintenance treatment of recurrent depression with sertraline versus episodic treatment with dothiepin.

PubMed

Hatziandreu, E J; Brown, R E; Revicki, D A; Turner, R; Martindale, J; Levine, S; Siegel, J E

1994-03-01

The objective of this study was to model, for patients at risk of recurrent depression, the cost-utility of maintenance therapy with sertraline compared with treatment of acute episodes with dothiepin ('episodic treatment'). Using clinical decision analysis techniques, a Markov state-transition model was constructed to estimate the lifetime costs and quality-adjusted life-years (QALYs) of the 2 therapeutic strategies. The model follows 2 cohorts of 35-year-old women at high risk for recurrent depression over their lifetimes. Model construction and relevant data (probabilities) for performing the analysis were based on existing clinical knowledge. Two physician panels were used to obtain estimates of recurrence probabilities not available in the literature, health utilities, and resource consumption. Costs were obtained from published sources. The baseline analysis showed that it costs 2172 British pounds sterling ($US3692, 1991 currency) to save an additional QALY with sertraline maintenance treatment. Sensitivity analysis showed that the incremental cost-utility ratio ranged from 557 British pounds sterling to 5260 British pounds sterling per QALY. Overall, the resulting ratios are considered to be well within the range of cost-utility ratios that support the adoption and appropriate utilisation of a technology. Based on the study assumptions, long term maintenance treatment with sertraline appears to be clinically and economically justified choice for patients at high risk of recurrent depression.

An algorithm for treatment of patients with hypersensitivity reactions after vaccines.

PubMed

Wood, Robert A; Berger, Melvin; Dreskin, Stephen C; Setse, Rosanna; Engler, Renata J M; Dekker, Cornelia L; Halsey, Neal A

2008-09-01

Concerns about possible allergic reactions to immunizations are raised frequently by both patients/parents and primary care providers. Estimates of true allergic, or immediate hypersensitivity, reactions to routine vaccines range from 1 per 50000 doses for diphtheria-tetanus-pertussis to approximately 1 per 500000 to 1000000 doses for most other vaccines. In a large study from New Zealand, data were collected during a 5-year period on 15 marketed vaccines and revealed an estimated rate of 1 immediate hypersensitivity reaction per 450000 doses of vaccine administered. Another large study, conducted within the Vaccine Safety Datalink, described a range of reaction rates to >7.5 million doses. Depending on the study design and the time after the immunization event, reaction rates varied from 0.65 cases per million doses to 1.53 cases per million doses when additional allergy codes were included. For some vaccines, particularly when allergens such as gelatin are part of the formulation (eg, Japanese encephalitis), higher rates of serious allergic reactions may occur. Although these per-dose estimates suggest that true hypersensitivity reactions are quite rare, the large number of doses that are administered, especially for the commonly used vaccines, makes this a relatively common clinical problem. In this review, we present background information on vaccine hypersensitivity, followed by a detailed algorithm that provides a rational and organized approach for the evaluation and treatment of patients with suspected hypersensitivity. We then include 3 cases of suspected allergic reactions to vaccines that have been referred to the Clinical Immunization Safety Assessment network to demonstrate the practical application of the algorithm.

Vaccine delivery management.

PubMed

Cheyne, J

1989-01-01

During the typical 12- to 18-month voyage of a vaccine from manufacturer to immunization site, many situations arise in which the cold chain may be interrupted. Extensive efforts have been made in the 1980s to ensure an uninterrupted cold chain through the use of improved equipment and better training of personnel. One important advance is the vaccine cold-chain monitor, which identifies weak spots in the cold chain and prevents the use of heat-damaged vaccine. Further improvements will require efforts by the recipient countries (e.g., better use of the private sector for transport and equipment management), by donor agencies (e.g., greater consideration of the operational and maintenance costs of the equipment selected and resolution of fuel shortages), and by industry (e.g., more appropriate packaging and pricing of vaccine, extension of the expiration period, and increased heat stability.

A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients.

PubMed

Rodriguez, Pedro C; Popa, Xitllaly; Martínez, Odeth; Mendoza, Silvia; Santiesteban, Eduardo; Crespo, Tatiana; Amador, Rosa M; Fleytas, Ricardo; Acosta, Soraida C; Otero, Yanine; Romero, Gala N; de la Torre, Ana; Cala, Mireysi; Arzuaga, Lina; Vello, Loisel; Reyes, Delmairis; Futiel, Niurka; Sabates, Teresa; Catala, Mauricio; Flores, Yoanna I; Garcia, Beatriz; Viada, Carmen; Lorenzo-Luaces, Patricia; Marrero, Maria A; Alonso, Liuba; Parra, Jenelin; Aguilera, Nadia; Pomares, Yaisel; Sierra, Patricia; Rodríguez, Gryssell; Mazorra, Zaima; Lage, Agustin; Crombet, Tania; Neninger, Elia

2016-08-01

EGFR is a well-validated target for patients with non-small cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF conjugated to a carrier protein and Montanide ISA51 as adjuvant. The vaccine is intended to induce antibodies against self EGFs that block EGF-EGFR interaction. To evaluate overall survival, safety, immunogenicity, and EGF concentration in serum after CIMAvax-EGF, a randomized phase III trial was done in patients with advanced NSCLC. Four to 6 weeks after first-line chemotherapy, 405 patients with stage IIIB/IV NSCLC were randomly assigned to a vaccine group, which received CIMAvax-EGF or a control group, treated with best supportive care. Long-term vaccination was very safe. Most frequent adverse reactions were grade 1 or 2 injection-site pain, fever, vomiting, and headache. Vaccination induced anti-EGF antibodies and decreased serum EGF concentration. In the safety population, median survival time (MST) was 10.83 months in the vaccine arm versus 8.86 months in the control arm. These differences were not significant according the standard log rank (HR, 0.82; P = 0.100), but according a weighted log rank (P = 0.04) that was applied once the nonproportionality of the HR was verified. Survival benefit was significant (HR, 0.77; P = 0.036) in the per-protocol setting (patients receiving at least four vaccine doses): MST was 12.43 months for the vaccine arm versus 9.43 months for the control arm. MST was higher (14.66 months) for vaccinated patients with high EGF concentration at baseline. Switch maintenance with CIMAvax-EGF was well tolerated and significantly increased MST of patients that completed induction vaccination. Baseline EGF concentration predicted survival benefit. Clin Cancer Res; 22(15); 3782-90. ©2016 AACR. ©2016 American Association for Cancer Research.

Persistent parasites and immunologic memory in cutaneous leishmaniasis: implications for vaccine designs and vaccination strategies.

PubMed

Okwor, Ifeoma; Uzonna, Jude

2008-01-01

Despite a plethora of publications on the murine model of cutaneous leishmaniasis and their contribution to our understanding of the factors that regulate the development of CD4+ T cell immunity in vivo, there is still no effective vaccine against the human disease. While recovery from natural or experimental infection with Leishmania major, the causative agent of human cutaneous leishmaniasis, results in persistence of parasites at the primary infection site and the development of long-lasting immunity to reinfection, vaccination with killed parasites or recombinant proteins induces only short-term protection. The reasons for the difference in protective immunity following recovery from live infection and vaccination with heat-killed parasites are not known. This may in part be related to persistence of live parasites following healing of primary cutaneous lesions, because complete clearance of parasites leads to rapid loss of infection-induced immunity. Recent reports indicate that in addition to persistent parasites, IL-10-producing natural regulatory T cells may also play critical roles in the maintenance and loss of infection-induced immunity. This review focuses on current understanding of the factors that regulate the development, maintenance and loss of anti-Leishmania memory responses and highlights the role of persistent parasites and regulatory T cells in this process. Understanding these factors is crucial for designing effective vaccines and vaccination strategies against cutaneous leishmaniasis.

Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment

PubMed Central

Hildesheim, Allan; Gonzalez, Paula; Kreimer, Aimee R.; Wacholder, Sholom; Schussler, John; Rodriguez, Ana C.; Porras, Carolina; Schiffman, Mark; Sidawy, Mary; Schiller, John T.; Lowy, Douglas R.; Herrero, Rolando

2016-01-01

BACKGROUND Human papillomavirus (HPV) vaccines prevent HPV infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an HPV-associated lesion is not fully understood. OBJECTIVES To determine whether HPV-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. STUDY DESIGN We included 1711 women (18–25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted HPV-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2+. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. RESULTS Median follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at

Evaluation of vaccine cold chain in urban health centers of municipal corporation of surat city, Western India.

PubMed

Naik, Ashish K; Rupani, Mihir P; Bansal, R K

2013-12-01

The success of immunization depends highly on the level of cold chain maintenance. The aim of the study was to assess the condition of cold chain equipment, practices adopted for cold chain maintenance and knowledge of the vaccinators. It was a cross-sectional study conducted in 20 UHCs of Surat Municipal Corporation (SMC). Cold chain equipment were observed with regards to their condition, along with the practices adopted by vaccinators for cold chain maintenance. A pre-designed and pre-tested questionnaire was used to interview the vaccinators regarding their knowledge and awareness regarding cold chain practices, management and handling. Data were entered and analyzed using Epi Info v 3.5.1. Simple proportions were calculated. Absence of separate stabilizer for deep freezers and ILRs (85%), ill-maintained temperature-record register, lack of criss-cross pattern of ice packs in deep freezer (65%), presence of things other than ice packs in deep freezer (10%) and things other than vaccines in ILR (10%) indicate poor cold chain maintenance. In addition to this, expired vaccines in ILR (5%), vaccines in the "unusable" stages of VVM (15%), lack of emergency contact number nearby in case of cold chain failure (85%), lack of inverter (85%), lack of generator (85%) and failure to note time of reconstitution on the vaccine vial at the time of vaccination (25%) indicate poor cold chain practices. Lack of knowledge of defrosting of ILR and deep freezer (45%), lack of knowledge about Shake test (40%), lack of knowledge of temperature range to be maintained in deep freezer (70%) and in ILR (15%) indicate poor knowledge of vaccinators. Cold chain maintenance and practices need improvement. Knowledge of vaccinators was overall unsatisfactory.

Yellow fever vaccination during treatment with infliximab in a patient with ulcerative colitis: A case report.

PubMed

Rüddel, J; Schleenvoigt, B T; Schüler, E; Schmidt, C; Pletz, M W; Stallmach, A

2016-09-01

We report the case of a 59-year-old patient who accidentally underwent live vaccination against yellow fever during continuous treatment with the TNF-α-antibody (AB) infliximab for ulcerative colitis. The clinical course showed fever of short duration and elevation of liver enzymes without further clinical complications. Yellow fever viremia was not detectable and protective antibodies were developed. A primary vaccination against yellow fever under infliximab has not been reported in the literature before, although vaccination is an important topic in IBD. Live vaccinations, like Stamaril(®) against yellow fever, are contraindicated during TNF-α-AB treatment. Treatment regimens containing TNF-α-AB are of growing importance, not only in gastroenterology, but also in rheumatology and dermatology. We discuss this topic by presenting our case and reviewing the current literature. © Georg Thieme Verlag KG Stuttgart · New York.

[Management of opioid maintenance treatments when analgesic treatments are required].

PubMed

Laprevote, Vincent; Geoffroy, Pierre A; Rolland, Benjamin; Leheup, Benoît F; Di Patrizio, Paolo; Cottencin, Olivier; Schwan, Raymund

2013-01-01

Opioid maintenance treatments (OMT) reduce illicit opiate use and its associated risks. They are often prescribed on a long-term basis. Physiological changes induced by long-term OMT may cause hyperalgesia and cross-tolerance to opioid agonists, which suggests that the dosage of analgesic treatment should be modified in cases of acute pain, especially when an opioid-based analgesia is required. When treatment with analgesics is necessary, OMT must be maintained, except in exceptional cases. If a split-dosing schedule is temporarily employed during OMT, the daily dosage should not be increased for analgesic purposes. Analgesic treatment must be managed differently in case of treatment with buprenorphine or methadone. With buprenorphine, non-opioid analgesics should be introduced first, if possible. If this strategy is inefficient or contraindicated, a temporary or definitive switch to methadone should be considered. In the case of methadone-based OMT, opioid analgesics should be added directly and the dosage should be adapted according to the level of pain reported by the patient. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Active opioid use does not attenuate the humoral responses to inactivated influenza vaccine

PubMed Central

Moroz, Ekaterina; Albrecht, Randy A.; Aden, Brandon; Beeder, Ann Bordwine; Yuan, Jianda; García-Sastre, Adolfo; Edlin, Brian R.; Salvatore, Mirella

2016-01-01

Background Influenza vaccination is recommended for vulnerable individuals, including active drug users, to prevent influenza complications and decrease influenza spread. Recent studies suggest that opioids negatively regulate immune responses in experimental models, but the extent to which opioid use will affect the humoral responses to influenza vaccine in humans is unknown. This information is critical in maximizing vaccination efforts. Objective To determine whether there is a difference in antibody response after influenza vaccination in heroin or methadone users compared to control subjects. Methods We studied active heroin users, subjects on methadone maintenance treatment (MMT) and subjects that did not use any drugs before and 1 and 4 weeks after vaccination with trivalent influenza vaccine (TIV). We measured hemagglutination inhibition and microneutralization titers, and we compared geometric mean titers (GMT), and rates of seroprotection and seroconversion for each of the vaccine strains among the 3 groups of subjects. Results Heroin users, subjects on MMT and non-user controls mount a similarly robust serologic response to TIV. GMT and rates of seroprotection and seroconversion were not significantly different among groups. Conclusion Our results suggest that opioid use do not significantly alter antibody responses to influenza vaccine supporting the vaccination effort in these populations. PMID:26859239

A single-dose antihelminthic treatment does not influence immunogenicity of a meningococcal and a cholera vaccine in Gabonese school children.

PubMed

Brückner, Sina; Agnandji, Selidji Todagbe; Elias, Johannes; Berberich, Stefan; Bache, Emmanuel; Fernandes, José; Loembe, Marguerite Massinga; Hass, Johanna; Lell, Bertrand; Mordmüller, Benjamin; Adegnika, Ayola Akim; Kremsner, Peter; Esen, Meral

2016-10-17

We recently described the effect of a single-dose antihelminthic treatment on vaccine immunogenicity to a seasonal influenza vaccine. Here we report the effect of antihelminthics on the immunogenicity of a meningococcal vaccine and a cholera vaccine in primary school children living in Lambaréné, Gabon. Since infection with helminths remains a major public health problem and the influence on cognitive and physical development as well as the immunomodulatory effects are well established, we investigated if a single-dose antihelminthic treatment prior to immunization positively influences antibody titers and vaccine-specific memory B-cells. In this placebo-controlled, double-blind trial the effect of a single-dose antihelminthic treatment prior to immunization with a meningococcal as well as with a cholera vaccine was investigated. Anti-meningococcal antibodies were assessed by serum bactericidal assay, cholera vaccine-specific antibody titers by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Day 0; vaccination), four weeks (Day 28) and 12weeks (Day 84) following vaccination. Meningococcal and cholera vaccine-specific memory B-cells were measured at Day 0 and 84 by vaccine-specific Enzyme-linked Immunospot (ELISpot) assay. The helminth burden of the participants was assessed four weeks before vaccination (Day -28) and at Day 84 by the Merthiolate-Iodine-Formaldehyde technique. Out of 280 screened school children, 96 received a meningococcal vaccine and 89 a cholera vaccine following allocation to either the single-dose antihelminthic treatment group or the placebo group. Bactericidal antibody titers increased following immunization with the meningococcal vaccine at Day 28 and Day 84 in 68 participants for serogroup A, and in 80 participants for serogroup C. The cholera vaccine titers increased in all participants with a peak at Day 28. The number of memory B-cells increased following vaccination compared to baseline. There was no statistically significant

Maintenance, Generalization, and Treatment Relapse: A Behavioral Momentum Analysis

ERIC Educational Resources Information Center

Mace, F. Charles; Nevin, John A.

2017-01-01

Maintenance and generalization have been inconsistently defined in the behavior analytic literature. The term "treatment relapse" is used commonly in the medical and mental health literature to refer to the return of a condition that was previously considered successfully treated. Basic behavioral researchers have studied relapse related…

Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B

PubMed Central

Noguera-Julian, Marc; Bellido, Rocío; Puertas, Maria C.; Carrillo, Jorge; Rodriguez, C.; Perez-Alvarez, Núria; Cobarsí, Patricia; Gomez, Carmen E.; Esteban, Mariano; Jímenez, Jose Luis; García, Felipe; Blanco, Julià; Martinez-Picado, Javier; Paredes, Roger

2017-01-01

The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control. Clinical parameters, proviral DNA, host HLA genetics and measures of humoral and cellular immunity were evaluated. A sieve effect analysis was conducted comparing pre-treatment viral sequences to breakthrough viruses after STI. Our results show that a reduced proviral HIV-1 DNA at study entry was independently associated with two virological parameters, delayed HIV-1 RNA rebound (p = 0.029) and lower peak viremia after treatment cessation (p = 0.019). Reduced peak viremia was also positively correlated with a decreased number of HLA class I allele associated polymorphisms in Gag sequences in the rebounding virus population (p = 0.012). Our findings suggest that proviral DNA levels and the number of HLA-associated Gag polymorphisms may have an impact on the clinical outcome of STI. Incorporation of these parameters in future therapeutic vaccine trials may guide refined immunogen design and help conduct safer STI approaches. PMID:28953921

Slow-release oral morphine for opioid maintenance treatment: a systematic review

PubMed Central

Jegu, Jeremie; Gallini, Adeline; Soler, Pauline; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse

2011-01-01

This review article summarizes the results of all available clinical trials considering the use of slow-release oral morphine (SROM) for opioid maintenance treatment (OMT). All studies published up to October 2010 and assessing SROM for OMT in adult patients are included. Three independent reviewers assessed the selected articles using a standardized checklist. Study design, study length and number of subjects included were recorded. Data about retention rate (proportion of participants remaining under maintenance treatment at the end of the study), quality of life, withdrawal symptoms, craving, additional drug consumption, driving capacity and adverse events were collected. We identified 13 articles corresponding to nine clinical trials considering the use of SROM for OMT. Among them, only one was a randomized trial and one was a controlled not randomized trial. All other studies were uncontrolled. Retention rates were good (from 80.6 to 95%) with SROM maintenance, but similar retention rates were obtained with methadone. Most of the studies showed that quality of life, withdrawal symptoms, craving and additional drug consumption improved with SROM. However, there was no comparison with other maintenance drugs. As most of the studies assessing SROM efficacy were uncontrolled, there is no definite evidence that SROM is an effective alternative to methadone for OMT. PMID:21265874

A field trial, of preshipment vaccination, with intranasal infectious bovine rhinotracheitis-parainfluenza-3 vaccines.

PubMed Central

Martin, W; Willson, P; Curtis, R; Allen, B; Acres, S

1983-01-01

A total of 849 calves, 278 controls, 335 vaccinated intranasally with IBR-PI3/TS and 236 vaccinated intranasally with IBR-PI3/PTC were studied in a field trial of preimmunization. All calves were vaccinated in Saskatchewan at least three weeks prior to shipment to feedlots. Four hundred and twenty six calves were not sold within eight weeks of vaccination; however, seven of these died within four weeks of vaccination. Treatment rates varied from 1.0% to 5.2%. There was no significant effect of vaccination on treatment rates. Similarly, there was no significant effect of vaccination in the 74 calves sold to feedlots in Saskatchewan. Three hundred and forty nine calves were sold to feedlots in Ontario. Two of these died from fibrinous pneumonia. Treatment rates varied from 1.7% to 33.3% in different feedlots, but there was no significant effect of vaccination on treatment rates. Therefore, preimmunization is unlikely to significantly reduce the overall treatment rate in calves entering feedlots. PMID:6315194

The development of global vaccine stockpiles.

PubMed

Yen, Catherine; Hyde, Terri B; Costa, Alejandro J; Fernandez, Katya; Tam, John S; Hugonnet, Stéphane; Huvos, Anne M; Duclos, Philippe; Dietz, Vance J; Burkholder, Brenton T

2015-03-01

Global vaccine stockpiles, in which vaccines are reserved for use when needed for emergencies or supply shortages, have effectively provided countries with the capacity for rapid response to emergency situations, such as outbreaks of yellow fever and meningococcal meningitis. The high cost and insufficient supply of many vaccines, including oral cholera vaccine and pandemic influenza vaccine, have prompted discussion on expansion of the use of vaccine stockpiles to address a wider range of emerging and re-emerging diseases. However, the decision to establish and maintain a vaccine stockpile is complex and must take account of disease and vaccine characteristics, stockpile management, funding, and ethical concerns, such as equity. Past experience with global vaccine stockpiles provide valuable information about the processes for their establishment and maintenance. In this Review we explored existing literature and stockpile data to discuss the lessons learned and to inform the development of future vaccine stockpiles. Copyright © 2015 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd. All rights reserved.

[Maintenance Treatment With Antipsychotics for Adult Patients Diagnosed With Schizophrenia].

PubMed

Gómez-Restrepo, Carlos; Bohórquez Peñaranda, Adriana Patricia; de la Hoz Bradford, Ana María; Tamayo Martínez, Nathalie; García Valencia, Jenny; Jaramillo González, Luis Eduardo

2014-01-01

To determine the effectiveness and security of the antipsychotics available for the management of adult patients with schizophrenia in the maintenance phase. To develop recommendations of treatment for the maintenance phase of the disease. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. 18 studies were included to evaluate the effectiveness and / or safety of different antipsychotic drugs first and second generation. Overall, antipsychotics (AP) showed superiority over placebo in relapse rate over 12 months (RR 0.59 95% CI 0.42, 0.82) and hospitalization rate over 24 months of follow-up (RR 0.38 95% 0.27, 0.55); its use is associated with increased risk of treatment dropout (RR 0.53 95% CI 0.46, 0.61) and adverse events such as weight gain, dystonia, extrapyramidal symptoms and sedation. There was no difference in the outcome of re hospitalizations, comparisons on quality of life, negative symptoms or weight gain between AP first and second generation. Continuous or standard dose regimens appear to be superior to intermittent or low doses in reducing the risk of abandonment of treatment regimes. Adult patients diagnosed with schizophrenia should receive maintenance treatment with antipsychotics. The medication of choice will depend on the management of the acute phase, the patient's tolerance to it and the presentation of adverse events. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Active Vaccines for Alzheimer Disease Treatment.

PubMed

Sterner, Rosalie M; Takahashi, Paul Y; Yu Ballard, Aimee C

2016-09-01

Vaccination against peptides specific to Alzheimer disease may generate an immune response that could help inhibit disease and symptom progression. PubMed and Scopus were searched for clinical trial articles, review articles, and preclinical studies relevant to the field of active Alzheimer disease vaccines and raw searches yielded articles ranging from 2016 to 1973. ClinicalTrials.gov was searched for active Alzheimer disease vaccine trials. Manual research and cross-referencing from reviews and original articles was performed. First generation Aβ42 phase 2a trial in patients with mild to moderate Alzheimer disease resulted in cases of meningoencephalitis in 6% of patients, so next generation vaccines are working to target more specific epitopes to induce a more controlled immune response. Difficulty in developing these vaccines resides in striking a balance between providing a vaccine that induces enough of an immune response to actually clear protein sustainably but not so much of a response that results in excess immune activation and possibly adverse effects such as meningoencephalitis. Although much work still needs to be done in the field to make this a practical possibility, the enticing allure of being able to treat or even prevent the extraordinarily impactful disease that is Alzheimer disease makes the idea of active vaccination for Alzheimer disease very appealing and something worth striving toward. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Maintenance plasma exchange treatment for muscle specific kinase antibody positive myasthenia gravis patients.

PubMed

Yamada, Chisa; Teener, James W; Davenport, Robertson D; Cooling, Laura

2015-10-01

Anti-muscle specific kinase antibody positive myasthenia gravis (MuSK MG) is often characterized by a relatively severe and progressive course, refractoriness to standard myasthenia gravis (MG) medications, and an increased risk of myasthenic crisis. We report here successful management of three MuSK MG patients using maintenance therapeutic plasma exchange (TPE) treatment for up to 4.5 years. The study was a 5-year retrospective review of all MG patients treated with TPE between 2008 and 2013 at University of Michigan. Inclusion criteria of MuSK MG were positive for anti-MuSK antibodies and a diagnosis of MuSK MG by staff neurologists. Patient data included age, gender, diagnostic testing results, medications, and the dates and response to TPE treatments. A total of 153 MG patients underwent at least one course of TPE between 2008 and 2013. A total of 12 patients (7.8%) were positive for anti-MuSK antibodies. Patients were predominantly female (83.3%) and a median age of onset was 46-years old. Three MuSK MG patients were successfully managed with maintenance TPE. Maintenance TPE may be an effective option for MuSK MG patients. The key of successful maintenance treatment at our institution has been to tailor the TPE frequency for each individual, and to modify the treatment interval in conjunction with medical management. © 2014 Wiley Periodicals, Inc.

Drug Treatment Combined with BCG Vaccination Reduces Disease Reactivation in Guinea Pigs Infected with Mycobacterium tuberculosis

PubMed Central

Shang, Shaobin; Shanley, Crystal A.; Caraway, Megan L.; Orme, Eileen A.; Henao-Tamayo, Marcela; Hascall-Dove, Laurel; Ackart, David; Orme, Ian M.; Ordway, Diane J.; Basaraba, Randall J.

2012-01-01

Bacillus-Calmette-Guerin (BCG), the only human tuberculosis vaccine, primes a partially protective immune response against M. tuberculosis infection in humans and animals. In guinea pigs, BCG vaccination slows the progression of disease and reduces the severity of necrotic granulomas, which harbor a population of drug-tolerant bacilli. The objective of this study was to determine if reducing disease severity by BCG vaccination of guinea pigs prior to M. tuberculosis challenge enhanced the efficacy of combination drug therapy. At 20 days of infection, treatment of vaccinated and non-vaccinated animals with rifampin, isoniazid, and pyrizinamide (RHZ) was initiated for 4 or 8 weeks. On days 50, 80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung leukocyte numbers by flow cytometry. In a separate, long-term survival study, treatment efficacy was evaluated by determining disease reactivation frequency post-mortem. BCG vaccination alone delayed pulmonary and extra-pulmonary disease progression, but failed to prevent dissemination of bacilli and the formation of necrotic granulomas. Drug therapy either alone or in combination with BCG, was more effective at lessening clinical disease and lesion severity compared to control animals or those receiving BCG alone. Fewer residual lesions in BCG vaccinated and drug treated animals, equated to a reduced frequency of reactivation disease and improvement in survival even out to 500 days of infection. The combining of BCG vaccination and drug therapy was more effective at resolving granulomas such that fewer animals had evidence of residual infection and thus less reactivation disease. PMID:22244979

Performance of preventive maintenance treatments for flexible pavements in Texas.

DOT National Transportation Integrated Search

2017-03-01

This report documents the work performed in the first year of the Texas Department of TxDOT Project 0-6878. : The main objective of this project is to quantify the effectiveness of various popular preventive maintenance : (PM) treatments under varyin...

Treatment of a long-acting anticoagulant rodenticide poisoning cohort with vitamin K1 during the maintenance period

PubMed Central

Long, Jianhai; Peng, Xiaobo; Luo, Yuan; Sun, Yawei; Lin, Guodong; Wang, Yongan; Qiu, Zewu

2016-01-01

Abstract Currently, there are few guidelines for the use of vitamin K1 in the maintenance treatment of long-acting anticoagulant rodenticide (LAAR) poisonings. We explored factors in the treatment of LAAR poisoning during the maintenance period in order to suggest feasible treatment models. Data from 24 cases of anticoagulant rodenticide poisoning in our hospital were collected from January 2013 to May 2016. The patients’ sex, age, coagulation function, total time from poisoning to treatment with vitamin K1 (prehospital time), vitamin K1 sustained treatment time (VKSTT), anticoagulant rodenticide category, and specific poison dosage were collected. Multivariate analysis was used to evaluate the correlation between vitamin K1 dosage and other factors during the maintenance period. Only VKSTT (partial regression coefficient −1.133, 0.59, P = 0.035) had an obvious influence on the therapeutic dose of vitamin K1 required during the maintenance period. After an initial pulse therapy, the bleeding and coagulation functions were stabilized, and the patients were subsequently treated with vitamin K1 during the maintenance period. Over time, the maintenance dose of vitamin K1 (10–120 mg/d, intravenous drip) was gradually decreased and was not related to toxicant concentration. PMID:28002326

Aripiprazole Long-Acting Injectable for Maintenance Treatment of Bipolar I Disorder in Adults.

PubMed

Aggarwal, Arpit; Schrimpf, Lindsey; Lauriello, John

2018-01-01

Bipolar I disorder is a serious and disabling psychiatric illness. It is associated with a significant reduction in quality of life and an increased risk for suicide. Pharmacotherapy is essential for both the acute and maintenance treatment of bi-polar I disorder. While multiple oral medications are recommended for the maintenance treatment, there are not many long-acting injectable medications approved for this indication. New treatments that would improve patient adherence have the potential for decreasing relapses and improving patients' ability to remain functional members of society. In this paper we discuss the available data for safety and efficacy of aripiprazole long-acting injectable in bipolar disorder.

Predicted outcomes of vaccinating wildlife to reduce human risk of Lyme disease.

PubMed

Tsao, Kimberly; Fish, Durland; Galvani, Alison P

2012-07-01

Vaccination efforts for Lyme disease prevention in humans have focused on wildlife reservoirs to target the causative agent, Borrelia burgdorferi, for elimination in vector ticks. Multiple host species are involved in the transmission and maintenance of the bacterium, but not all host species can be vaccinated effectively. To evaluate vaccinating a subset of hosts in the context of host-tick interactions, we constructed and evaluated a dynamic model of B. burgdorferi transmission in mice. Our analyses indicate that on average, a mouse-targeted vaccine is expected to proportionally reduce infection prevalence among ticks by 56%. However, relative to mouse vaccination, human risk of exposure is dominated by the number of tick bites received per person, the proportion of tick blood meals taken from the highly reservoir-competent white-footed mouse relative to other hosts, and the average number of tick bites per mouse. Variation in these factors reduces the predictability of vaccination outcomes. Additionally, contributions of nonmouse hosts to pathogen maintenance preclude elimination of B. burgdorferi through mouse vaccination alone. Our findings indicate that to increase the impact of wildlife vaccination, reducing tick populations by acaricide application, in addition to targeting additional reservoir-competent host species, should be employed.

[Efficacy of the administration of serum amd vaccine for the antirabies treatment of experimentally-infected sheep].

PubMed

Soria Baltazar, R; Blancou, J

1995-09-01

The objectives of this study were to examine the humoral immune response of sheep to experimental infection with an isolate of rabies virus from a fox, to analyse the efficacy of vaccination as a method of post-infection treatment, and to find a suitable animal model to evaluate new procedures for human vaccination following infection. A total of 47 sheep were used. Initially, 26 sheep received an intramuscular injection of a suspension of virus (titre: 10(6.8) 50% lethal dose for mice by the intracerebral route). Half of the sheep were subsequently treated using a vaccine on the day of infection and at 3, 7, 14 and 30 days post-infection. The remaining half comprised the unvaccinated controls. This vaccination protected seven of thirteen sheep, while nine of the thirteen controls died. Subsequently, 21 sheep were inoculated under the same conditions as in the previous trial. The animals were divided into three groups of seven animals each. The first group was vaccinated in the same way as described above. The second group received an injection of anti-rabies immunoglobulin of human origin (26.3 IU/kg of body weight), followed by the course of vaccine treatment 24 hours later. The remaining group acted as unvaccinated controls. Of the seven sheep given vaccine alone, four were protected, while all seven animals given immunoglobulin and vaccine were protected. Six of the seven untreated controls died. In this study, no apparently-healthy carriers of rabies virus were created by any of the treatments used, nor was there any shortening of the incubation periods. Additional observations were made concerning incubation periods and the course of the disease, as well as symptoms, lesions and the presence of rabies virus in various nerve centres and salivary glands of the experimental sheep.

Operation, Maintenance and Management of Wastewater Treatment Facilities: A Bibliography of Technical Documents.

ERIC Educational Resources Information Center

Himes, Dottie

This is an annotated bibliography of wastewater treatment manuals. Fourteen manuals are abstracted including: (1) A Planned Maintenance Management System for Municipal Wastewater Treatment Plants; (2) Anaerobic Sludge Digestion, Operations Manual; (3) Emergency Planning for Municipal Wastewater Treatment Facilities; (4) Estimating Laboratory Needs…

Leukocytapheresis (LCAP) for the treatment of rheumatoid arthritis on a maintenance hemodialysis patient.

PubMed

Ohsawa, I; Ohi, H; Maruyama, T; Hamada, H; Tomino, Y

2007-08-01

A 57-year-old-woman, who was treated with regular maintenance hemodialysis (HD), newly contracted rheumatoid arthritis (RA). Oral predonisolone was effective for alleviating her arthralgia but the RA activity became steroid-dependent. For treatment of poorly controlled synovitis leukocytapheresis (LCAP) showed excellent efficacy in the treatment of her joint pain. No serious adverse effects were observed. Serological markers such as CRP, serum amyloid A, matrix metalloproteinase 3 and peripheral blood lymphocyte count fluctuated with her clinical symptoms. We recommend LCAP as candidate therapy for steroid-dependent patients with RA who are on maintenance HD.

Current and Potential Pharmacological Treatment Options for Maintenance Therapy in Opioid-Dependent Individuals

PubMed Central

Tetrault, Jeanette M.; Fiellin, David A.

2013-01-01

Opioid dependence, manifesting as addiction to heroin and pharmaceutical opioids is increasing. Internationally, there are an estimated 15.6 million illicit opioid users. The global economic burden of opioid dependence is profound both in terms of HIV and hepatitis C virus transmission, direct healthcare costs, and indirectly through criminal activity, absenteeism and lost productivity. Opioid agonist medications, such as methadone and buprenorphine, that stabilize neuronal systems and provide narcotic blockade are the most effective treatments. Prolonged provision of these medications, defined as maintenance treatment, typically produces improved outcomes when compared with short-duration tapers and withdrawal. The benefits of opioid agonist maintenance include decreased illicit drug use, improved retention in treatment, decreased HIV risk behaviours and decreased criminal behaviour. While regulations vary by country, these medications are becoming increasingly available internationally, especially in regions experiencing rapid transmission of HIV due to injection drug use. In this review, we describe the rationale for maintenance treatment of opioid dependence, discuss emerging uses of opioid antagonists such as naltrexone, and sustained-release formulations of naltrexone and buprenorphine, and provide a description of the experimental therapies. PMID:22235870

Medicaid Coverage for Methadone Maintenance and Use of Opioid Agonist Therapy in Specialty Addiction Treatment.

PubMed

Saloner, Brendan; Stoller, Kenneth B; Barry, Colleen L

2016-06-01

This study examined differences in opioid agonist therapy (OAT) utilization among Medicaid-enrolled adults receiving public-sector opioid use disorder treatment in states with Medicaid coverage of methadone maintenance, states with block grant funding only, and states without public coverage of methadone. Person-level treatment admission data, which included information on reason for treatment and use of OAT from 36 states were linked to state-level Medicaid policies collected in a 50-state survey. Probabilities of OAT use among Medicaid enrollees in opioid addiction treatment were calculated, with adjustment for demographic characteristics and patterns of substance use. In adjusted analysis, 45.0% of Medicaid-enrolled individuals in opioid addiction treatment in states with Medicaid coverage for methadone maintenance used OAT, compared with 30.1% in states with block grant coverage only and 17.0% in states with no coverage. Differences were widest in nonintensive outpatient settings. Medicaid methadone maintenance coverage is critical for encouraging OAT among individuals with opioid use disorders.

Intralesional Mycobacterium w Vaccine Versus Cryotherapy in Treatment of Refractory Extragenital Warts: A Randomized, Open-Label, Comparative Study.

PubMed

Dhakar, Ashok K; Dogra, Sunil; Vinay, Keshavamurthy; Sarangal, Rishu; Kanwar, Amrinder J; Singh, Mini P

2016-01-01

Initial reports of immunotherapy using intralesional Mycobacterium w (Mw) vaccine have documented its useful role in treatment of genital and extragenital warts. To compare the efficacy and safety of intralesional Mw vaccine versus cryotherapy in the treatment of refractory extragenital warts. This was a prospective, randomized, comparative study of 66 patients. The outcome was assessed in terms of complete clearance of warts and change in Dermatology Life Quality Index (DLQI) score. Complete clearance of treated warts was seen in 66.7% (20/30) and 65.5% (19/29) of patients in the Mw and cryotherapy groups, respectively (P = .769). Clearance of distant warts was significantly (P = .004) high in the Mw group. Improvement in DLQI was greater in the Mw group. Both treatment modalities were well tolerated, and no major side effects occurred. Mw vaccine and cryotherapy are equally efficacious in treatment of refractory extragenital warts. Mw vaccine has an added advantage of clearance of distant warts. © The Author(s) 2015.

Vaccines and immunotherapeutics for the prevention and treatment of infections with West Nile virus.

PubMed

Beasley, David W C

2011-02-01

The emergence of West Nile virus (WNV) in North America in 1999 as a cause of severe neurological disease in humans, horses and birds stimulated development of vaccines for human and veterinary use, as well as polyclonal/monoclonal antibodies and other immunomodulating compounds for use as therapeutics. Although disease incidence in North America has declined since the peak epidemics in 2002-2003, the virus has continued to be annually transmitted in the Americas and to cause periodic epidemics in Europe and the Middle East. Continued transmission of the virus with human and animal disease suggests that vaccines and therapeutics for the prevention and treatment of WNV disease could be of great benefit. This article focuses on progress in development and evaluation of vaccines and immunotherapeutics for the prevention and treatment of WNV disease in humans and animals.

[The financial impact of maintenance treatment in heroin addictive behavior: the case of Subutex].

PubMed

Kopp, P; Rumeau-Pichon, C; Le Pen, C

2000-06-01

The development of maintenance treatment for subjects with addictive behavior is an important public health issue. As such, the social effectiveness of maintenance products must be examined from an economical and social point of view. This paper aims at presenting the financial costs involved in the use of Subutex, a product commercialized since 1996. A complete typology of costs related to drug addiction and its consequences was set up. Some of these costs were estimated on the basis of data drawn from the literature. The cost of Subutex use for maintenance treatment was assessed and compared with the financial stakes including the potential reduction of the economic and social cost of drug addiction. Monthly treatment cost of Subutex was 1252 FrF per drug abuser on maintenance treatment. By extrapolation, for a population of 40,000 drug abusers, the direct medical cost of Subutex during a course of maintenance treatment with general practitioner follow-up was estimated at 600 millions FrF. US data sources were applied to France to assess the cost of illnesses attributable to drug addiction. The cost reached 4.8 billions FrF. The cost of delinquency associated with drug addiction, which mostly concerns money laundered to purchase substances was an estimated 6.4 billions FrF. Finally, the cost of public anti-drug abuse programs was nearly 4.7 billions FrF. Thus, the direct cost of drug addiction consequences reached 15.6 billions FrF. This cost should be compared with the annual cost of Subutex for public organizations which was an estimated 600 millions FrF. The "profit" threshold of maintenance treatment with Subutex in terms of direct costs is very low. A decrease of only 4% of the costs associated with drug addiction would make it possible to balance the financial budget for the community. Our analysis does not take into acount absolutely all the public health and safety aspects involved in the use of Subutex. It does however provide a useful assessment of the

[Treatment of lymphedema in institutions. Two weeks of in-hospital intensive lymphatic drainage followed by maintenance treatment with a pulsator].

PubMed

Walby, R

1990-10-10

54 patients were admitted to The Norwegian Radium Hospital (hotel ward) for treatment of secondary lymph drainage in the arm or the leg. The treatment consisted of 14 days intensive lymph drainage, including massage and physical exercises, and intermittent compression with pulsator and bandaging. Information/instruction was given continuously. Good elastic stockings were supplied before the patients left the hospital. The treatment was succeeded by a maintenance programme, which the patients carried out themselves at home. The patients were closely followed up and reported on for six months, and were rechecked after another four and 12 months. We present the results after 14 days of intense treatment, followed by a 12-month maintenance programme.

Periodontal and periimplant maintenance: a critical factor in long-term treatment success.

PubMed

Shumaker, Nicholas D; Metcalf, Brett T; Toscano, Nicholas T; Holtzclaw, Dan J

2009-09-01

Periodontal maintenance (PM) is a critical factor in the long-term success of both periodontal and dental implant therapy. Studies have shown both modern periodontal and dental implant therapies are effective in maintaining natural teeth and replacing lost teeth, respectively. However, without a regular program of clinical reevaluation, plaque control, oral hygiene instruction, and reassessment of biomechanical factors, the benefits of treatment often are lost and inflammatory disease in the form of recurrent periodontitis or periimplantitis may result. This article reviews the goals, types, and appropriate frequency of PM in periodontal and dental implant therapy, as well as the incidence and etiology of periimplant disease and strategies for management when recurrent disease develops during the maintenance phase of treatment.

Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

PubMed Central

Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A.; Riecher-Rössler, Anita; Lang, Undine E.; Borgwardt, Stefan

2015-01-01

Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of

Physician Peer Assessments for Compliance with Methadone Maintenance Treatment Guidelines

ERIC Educational Resources Information Center

Strike, Carol; Wenghofer, Elizabeth; Gnam, William; Hillier, Wade; Veldhuizen, Scott; Millson, Margaret

2007-01-01

Introduction: Medical associations and licensing bodies face pressure to implement quality assurance programs, but evidence-based models are lacking. To improve the quality of methadone maintenance treatment (MMT), the College of Physicians and Surgeons of Ontario, Canada, conducts an innovative quality assurance program on the basis of peer…

Assessing the impact of wastage on pediatric vaccine immunization formulary costs using a vaccine selection algorithm.

PubMed

Jacobson, Sheldon H; Karnani, Tamana; Sewell, Edward C

2004-06-02

Pediatric immunization is an important factor in providing protection against numerous common preventable diseases. The success of the pharmaceutical industry in developing new pediatric vaccines has resulted in a crowded recommended immunization schedule requiring several clinic visits over the first 12 years of life. Operations research models have been developed and used to make economically sound procurement choices from among a growing number of competing vaccine products. One factor that has not been incorporated into such models is the economic impact of wastage on such decisions. This paper reports results obtained from a vaccine selection algorithm that incorporates vaccine wastage data. The lowest overall cost formularies comparing no wastage costs with wastage costs are presented. A sensitivity analysis of the vaccine formulary with respect to the wastage rates associated with each available vaccine is provided. The maximum permissible wastage rate for each vaccine is determined for which the vaccine earns a place in the lowest overall cost formulary. This research provides health maintenance organizations and healthcare providers information that can be used to gain a better understanding of wastage and its impact on pediatric formulary costs.

Human Vaccines & Immunotherapeutics

PubMed Central

Riedmann, Eva M.

2012-01-01

Two therapeutic HPV vaccine candidates successful in phase 1 Flu shot may prevent heart attacks and stroke CDX-1401 combined with TLR agonist: Positive phase 1 results Three MRSA vaccines in early clincial trials Ovarian cancer vaccine candidate DPX-Survivac: Positive interim results from phase 1 Chinese biotech partnership brings first hepatitis E vaccine to the market Therapeutic vaccine for treatment of genital herpes enters phase 2 Visionary concept: Printable vaccines PMID:23817319

Object relations and differential treatment response to methadone maintenance.

PubMed

Nicholson, B; Treece, C

1981-07-01

The authors report results from a psychiatric study of narcotic addicts in which the relationship between specified aspects of object relations development and treatment response to methadone maintenance was examined. Two groups were defined as high and low drug users (in addition to the prescribed methadone dose) depending upon the frequency and intensity of additional drug use; a middle group was excluded. Thirty subjects participated. The dimensions of separation/individuation, narcissistic development, and self and object representations were measured by 12 scaled variables; scores of the high and low drug users were compared by t-test. In all cases, the high use group was found to be more impaired than the low use group. However, the dimensions differed greatly in their ability to differentiate the groups. The strongest group differences were found in the area of narcissistic development, with the high user group significantly more impaired than the low user group. The strength of these findings lends empirical support to the notion that an addict population can be differentiated on diagnostic and ego psychological measures. This has important implications for methadone maintenance treatment programs, and, possibly, for drug programs in general.

[Maintenance electroconvulsive therapy and treatment of refractory schizophrenia].

PubMed

Lévy-Rueff, M; Jurgens, A; Lôo, H; Olié, J-P; Amado, I

2008-10-01

Electroconvulsive therapy, a standard treatment in mood disorders, is sometimes also indicated in psychotic disorders, especially in the treatment of refractory schizophrenia. In this instance, maintenance electroconvulsive therapy (M-ECT) can also become a long-term treatment. This paper presents the effects of M-ECT in the treatment of refractory schizophrenia using a retrospective analysis. Previous works showed that electroconvulsive therapy is effective on catatonia, anxiety with somatisation, lack of compliance, opposition, delusions especially with hallucinations and persecution, anorexia, agitation, carelessness, aggressive behaviour and moral pain. It is ineffective on bewilderment, somatic complaints and negative symptoms. A retrospective analysis of a clinical cohort of patients treated with M-ECT was carried out to determine the specific indications of M-ECT, its effectiveness on clinical symptoms, quality of life, relapse rates and use of medication. Nineteen patients with DSM-IV diagnosis of paranoid schizophrenia (n=5), schizophrenia with neurotic symptoms (n=3), disorganized schizophrenia (n=1), hebephrenia (n=3) and schizoaffective disorder (n=8), treated in the department of the University Hospital of Sainte-Anne in Paris, received M-ECT between 1991 and 2005. Seven patients are still under this treatment. Their mean age at the beginning of treatment was 47.5 years with a mean duration of the illness of 24 years. The indication of M-ECT was the increase of acute episodes, an increase of symptoms intensity, the inefficiency or intolerance to pharmacological treatments or an early relapse after ECT discontinuation. All patients had previously been successfully treated by ECT during an acute episode. Each patient received an average of 47 bilateral M-ECT under general anaesthesia at one to five weeks' intervals for a mean period of 43 months. All of them were also treated by antipsychotics; in addition, 30% received mood stabilizers and 10

Alternatives to lithium and divalproex in the maintenance treatment of bipolar disorder.

PubMed

Gnanadesikan, Mukund; Freeman, Marlene P; Gelenberg, Alan J

2003-06-01

The role of lithium carbonate in the maintenance treatment of bipolar disorder is well established. Unfortunately, many patients fail to respond adequately to this agent or are unable to tolerate its adverse effects. Divalproex has become a commonly used alternative to lithium, but it also is ineffective or poorly tolerated in many patients. This article attempts to review the available data on maintenance therapy in bipolar disorder with a variety of anticonvulsants and antipsychotics (both conventional and novel), with reference to relevant studies in acute mania and bipolar depression as well. Evidence on maintenance therapy and relevant acute-phase data were collected using MEDLINE database searches. Data on maintenance therapy with agents other than lithium and divalproex are sparse, and often derived from open, uncontrolled studies. Implications and flaws of available data are discussed. Other than lithium, there are few robust double-blind data to support the use of a variety of agents in the maintenance phase. However, uncontrolled data suggest that a number of agents merit further study.

Aripiprazole once-monthly as maintenance treatment for bipolar I disorder: a 52-week, multicenter, open-label study.

PubMed

Calabrese, Joseph R; Jin, Na; Johnson, Brian; Such, Pedro; Baker, Ross A; Madera, Jessica; Hertel, Peter; Ottinger, Jocelyn; Amatniek, Joan; Kawasaki, Hiroaki

2018-06-10

The long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I. This open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive ("de novo") patients as well as AOM 400-experienced ("rollover") patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324-331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder-Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified. Of 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (< 10% of patients). Patient satisfaction levels were high, with both

Relationship between vaccine vial monitors and cold chain infrastructure in a rural district of India.

PubMed

Samant, Y; Lanjewar, H; Parker, L; Block, D; Stein, B; Tomar, G

2007-01-01

The potency of oral polio vaccine (OPV), a heat-labile vaccine, is preserved by the cold chain. The Vaccine Vial Monitor, a heat-sensitive label, is critical to the monitoring and maintenance of the cold chain. This study was conducted to evaluate the relationship between the adequacy of cold chain infrastructure and the proper use of Vaccine Vial Monitor in a rural district of India. Forty-six health centers in a rural district were included in our evaluation of the cold chain equipment and the Vaccine Vial Monitors. Cold chain equipment and vaccine vials within each health center were evaluated for adherence to WHO cold chain maintenance protocols and the Vaccine Vial Monitor stage, respectively. Among the 46 health centers, Vaccine Vial Monitor stage I was found at 58% of the health centers, 33% of the health centers reported stage II and 9% reported a stage III, indicating weaknesses in the cold chain mechanism Cold chain for the OPV was not adequately maintained at primary and sub-health centers in this rural district. Well maintained ice packs and vaccine carriers will help ensure delivery and availability of a safe and potent vaccine to children in rural areas of India.

Cervical cancer treatment costs and cost-effectiveness analysis of human papillomavirus vaccination in Vietnam: a PRIME modeling study.

PubMed

Van Minh, Hoang; My, Nguyen Thi Tuyet; Jit, Mark

2017-05-15

Cervical cancer is currently the leading cause of cancer mortality among women in South Vietnam and the second leading cause of cancer mortality in North Vietnam. Human papillomavirus (HPV) vaccination has the potential to substantially decrease this burden. The World Health Organization (WHO) recommends that a cost-effectiveness analysis of HPV vaccination is conducted before nationwide introduction. The Papillomavirus Rapid Interface for Modeling and Economics (PRIME) model was used to evaluate the cost-effectiveness of HPV vaccine introduction. A costing study based on expert panel discussions, interviews and hospital case note reviews was conducted to explore the cost of cervical cancer care. The cost of cervical cancer treatment ranged from US$368 - 11400 depending on the type of hospital and treatment involved. Under Gavi-negotiated prices of US$4.55, HPV vaccination is likely to be very cost-effective with an incremental cost per disability-adjusted life year (DALY) averted in the range US$780 - 1120. However, under list prices for Cervarix and Gardasil in Vietnam, the incremental cost per DALY averted for HPV vaccination can exceed US$8000. HPV vaccine introduction appears to be economically attractive only if Vietnam is able to procure the vaccine at Gavi prices. This highlights the importance of initiating a nationwide vaccination programme while such prices are still available.

Social facilitation maintenance treatment for adults with obesity: study protocol for a randomised-controlled feasibility study (SFM study).

PubMed

Hilbert, Anja

2016-08-31

The long-term success of non-surgical weight loss treatment in adults with obesity is limited by substantial relapse, and only a few evidence-based weight loss maintenance treatments exist. This clinical trial investigates the feasibility and efficacy of a social facilitation maintenance programme for weight loss maintenance, tailored to meet the needs of obese adults who have undergone a lifestyle weight loss intervention. In a single-centre, open feasibility trial, 72 adults currently or previously obese or overweight who have undergone a lifestyle weight loss intervention are centrally randomised to 4 months of social facilitation maintenance treatment or treatment as a usual control condition. In 16 outpatient group sessions, the social facilitation maintenance treatment, based on a socioecological model and on evidence supporting social facilitation as a key process in maintaining weight loss, focuses on promoting interpersonal relationships to build up a healthy lifestyle for long-term weight loss maintenance. Primary outcome is the amount of weight regain at 6-month follow-up, compared with pre-treatment weight, derived from measured body weight. Secondary outcomes address feasibility, including recruitment, attrition, assessment non-completion, compliance and patients' programme evaluation; and in comparison with pre-weight loss maintenance, social and interpersonal functioning, eating behaviour and physical activity, psychological and physical symptoms, body composition and risk of comorbidity, and quality of life at post-treatment and follow-up assessments. The study was approved by the Ethical Committee at the University of Leipzig (165-13-15072013). The study results will be disseminated through peer-reviewed publications. DRKS00005182. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Progress and novel strategies in vaccine development and treatment of anthrax.

PubMed

Chitlaru, Theodor; Altboum, Zeev; Reuveny, Shaul; Shafferman, Avigdor

2011-01-01

The lethal anthrax disease is caused by spores of the gram-positive Bacillus anthracis, a member of the cereus group of bacilli. Although the disease is very rare in the Western world, development of anthrax countermeasures gains increasing attention due to the potential use of B. anthracis spores as a bio-terror weapon. Protective antigen (PA), the non-toxic subunit of the bacterial secreted exotoxin, fulfills the role of recognizing a specific receptor and mediating the entry of the toxin into the host target cells. PA elicits a protective immune response and represents the basis for all current anthrax vaccines. Anti-PA neutralizing antibodies are useful correlates for protection and for vaccine efficacy evaluation. Post exposure anti-toxemic and anti-bacteremic prophylactic treatment of anthrax requires prolonged antibiotic administration. Shorter efficient postexposure treatments may require active or passive immunization, in addition to antibiotics. Although anthrax is acknowledged as a toxinogenic disease, additional factors, other than the bacterial toxin, may be involved in the virulence of B. anthracis and may be needed for the long-lasting protection conferred by PA immunization. The search for such novel factors is the focus of several high throughput genomic and proteomic studies that are already leading to identification of novel targets for therapeutics, for vaccine candidates, as well as biomarkers for detection and diagnosis. © 2010 John Wiley & Sons A/S.

Infrequent Illicit Methadone Use Among Stimulant-Using Patients in Methadone Maintenance Treatment Programs: A National Drug Abuse Treatment Clinical Trials Network Study

PubMed Central

Wu, Li-Tzy; Blazer, Dan G.; Stitzer, Maxine L.; Patkar, Ashwin A.; Blaine, Jack D.

2009-01-01

We sought to determine the prevalence, patterns, and correlates of past-month illicit methadone use and history of regular illicit use among stimulant-using methadone maintenance treatment patients. We obtained self-reported information on illicit methadone use from 383 participants recruited from six community-based methadone maintenance programs. Overall, 1.6% of participants reported illicit use in the past month, and 4.7% reported a history of regular use. Younger age and history of outpatient psychological treatment were associated with increased odds of past-month illicit use. Illicit methadone use among patients in maintenance programs is infrequent; however, a number of factors may increase risk of illicit use. PMID:18612886

Assessment of vaccination coverage, vaccination scar rates, and smallpox scarring in five areas of West Africa.

PubMed

Henderson, R H; Davis, H; Eddins, D L; Foege, W H

1973-01-01

In 1966, nineteen countries of West and Central Africa began a regional smallpox eradication and measles control programme in cooperation with the World Health Organization. This paper summarizes sample survey data collected to assess the results of the programme in Northern Nigeria (Sokoto and Katsina Provinces), Western Nigeria, Niger, Dahomey, and Togo. These data indicate that the programme, which used mass vaccination campaigns based on a collecting-point strategy, was generally successful in reaching a high proportion of the population. Analysis of vaccination coverage and vaccination scar rates by age underlined the importance to the programme of newborn children who accumulate rapidly following the mass campaign. Of all persons without vaccination scars at the time of the surveys, 34.4% were under 5 years of age; in the absence of a maintenance programme, this figure would rise to 40% after 1 year.

Medicaid Coverage of Methadone Maintenance and the Use of Opioid Agonist Therapy Among Pregnant Women in Specialty Treatment.

PubMed

Bachhuber, Marcus A; Mehta, Pooja K; Faherty, Laura J; Saloner, Brendan

2017-12-01

Opioid agonist therapy (OAT) is the standard of care for pregnant women with opioid use disorder (OUD). Medicaid coverage policies may strongly influence OAT use in this group. To examine the association between Medicaid coverage of methadone maintenance and planned use of OAT in the publicly funded treatment system. Retrospective cross-sectional analysis of treatment admissions in 30 states extracted from the Treatment Episode Data Set (2013 and 2014). Medicaid-insured pregnant women with OUD (n=3354 treatment admissions). The main outcome measure was planned use of OAT on admission. The main exposure was state Medicaid coverage of methadone maintenance. Using multivariable logistic regression models adjusting for sociodemographic, substance use, and treatment characteristics, we compared the probability of planned OAT use in states with Medicaid coverage of methadone maintenance versus states without coverage. A total of 71% of pregnant women admitted to OUD treatment were 18-29 years old, 85% were white non-Hispanic, and 56% used heroin. Overall, 74% of admissions occurred in the 18 states with Medicaid coverage of methadone maintenance and 53% of admissions involved planned use of OAT. Compared with states without Medicaid coverage of methadone maintenance, admissions in states with coverage were significantly more likely to involve planned OAT use (adjusted difference: 32.9 percentage points, 95% confidence interval, 19.2-46.7). Including methadone maintenance in the Medicaid benefit is essential to increasing OAT among pregnant women with OUD and should be considered a key policy strategy to enhance outcomes for mothers and newborns.

Development of Leishmania vaccines: predicting the future from past and present experience

PubMed Central

Mutiso, Joshua Muli; Macharia, John Chege; Kiio, Maria Ndunge; Ichagichu, James Maina; Rikoi, Hitler; Gicheru, Michael Muita

2013-01-01

Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. Resistance to infection is associated with a T-helper-1 immune response that activates macrophages to kill the intracellular parasite in a nitric oxide-dependent manner. Conversely, disease progression is generally associated with a T-helper-2 response that activates humoral immunity. Current control is based on chemotherapeutic treatments which are expensive, toxic and associated with high relapse and resistance rates. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-attenuated strains of Leishmania. However, to date, no vaccine is available despite substantial efforts by many laboratories. Major impediments in Leishmania vaccine development include: lack of adequate funding from national and international agencies, problems related to the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune responses and generation and maintenance of the immunological memory, an important but least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on the progress of the search for an effective vaccine against human and canine leishmaniasis. PMID:23554800

Maintenance or non-maintenance therapy in the treatment of advanced non-small cell lung cancer: that is the question.

PubMed

Galetta, D; Rossi, A; Pisconti, S; Millaku, A; Colucci, G

2010-11-01

Lung cancer is the most common cancer worldwide with non-small cell lung cancer (NSCLC), including squamous carcinoma, adenocarcinoma and large cell carcinoma, accounting for about 85% of all lung cancer types with most of the patients presenting with advanced disease at the time of diagnosis. In this setting first-line platinum-based chemotherapy for no more than 4-6 cycles are recommended. After these cycles of treatment, non-progressing patients enter in the so called "watch and wait" period in which no further therapy is administered until there is disease progression. In order to improve the advanced NSCLC outcomes, the efficacy of further treatment in the "watch and wait" period was investigated. This is the "maintenance therapy". Recently, the results coming from randomized phase III trials investigating two new agents, pemetrexed and erlotinib, in this setting led to their registration for maintenance therapy. Here, we report and discuss these results. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effects of lower-cost incentives on stimulant abstinence in methadone maintenance treatment: a National Drug Abuse Treatment Clinical Trials Network study.

PubMed

Peirce, Jessica M; Petry, Nancy M; Stitzer, Maxine L; Blaine, Jack; Kellogg, Scott; Satterfield, Frank; Schwartz, Marion; Krasnansky, Joe; Pencer, Eileen; Silva-Vazquez, Lolita; Kirby, Kimberly C; Royer-Malvestuto, Charlotte; Roll, John M; Cohen, Allan; Copersino, Marc L; Kolodner, Ken; Li, Rui

2006-02-01

Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence have improved treatment outcomes of substance abusers, but have not been widely implemented in community drug abuse treatment settings. To compare outcomes achieved when a lower-cost prize-based contingency management treatment is added to usual care in community methadone hydrochloride maintenance treatment settings. Random assignment to usual care with (n = 198) or without (n = 190) abstinence incentives during a 12-week trial. Six community-based methadone maintenance drug abuse treatment clinics in locations across the United States. Three hundred eighty-eight stimulant-abusing patients enrolled in methadone maintenance programs for at least 1 month and no more than 3 years. Participants submitting stimulant- and alcohol-negative samples earned draws for a chance to win prizes; the number of draws earned increased with continuous abstinence time. Total number of stimulant- and alcohol-negative samples provided, percentage of stimulant- and alcohol-negative samples provided, longest duration of abstinence, retention, and counseling attendance. Submission of stimulant- and alcohol-negative samples was twice as likely for incentive as for usual care group participants (odds ratio, 1.98; 95% confidence interval, 1.42-2.77). Achieving 4 or more, 8 or more, and 12 weeks of continuous abstinence was approximately 3, 9, and 11 times more likely, respectively, for incentive vs usual care participants. Groups did not differ on study retention or counseling attendance. The average cost of prizes was 120 dollars per participant. An abstinence incentive approach that paid 120 dollars in prizes per participant effectively increased stimulant abstinence in community-based methadone maintenance treatment clinics.

Addiction treatment-related Employment barriers: the impact of methadone maintenance

PubMed Central

Richardson, Lindsey; Wood, Evan; Montaner, Julio; Kerr, Thomas

2012-01-01

Employment is commonly upheld as an important outcome of addiction treatment. To explore this attribution we assessed whether treatment enrolment predicts employment initiation among participants enrolled in a community-recruited Canadian cohort of people who inject drugs (IDU) (n=1579). Survival analysis initially found no association between addiction treatment enrolment and employment initiation. However, when methadone maintenance therapy (MMT) was separated from other treatment modalities, non-MMT treatment positively predicted employment transitions, while MMT was negatively associated with employment initiation. Sub-analyses examining transitions into temporary, informal and under-the-table income generation echo these results. Findings suggest that individual factors impacting employment transitions may systematically apply to MMT clients, and that, in this setting, the impact of treatment on employment outcomes is contingent on treatment type and design. Treatment-specific differences underscore the need to expand low-threshold MMT, explore MMT alternatives and evaluate the impact of treatment design on the social and economic activity of IDU. PMID:22301085

Improving vaccination cold chain in the general practice setting.

PubMed

Page, Sue L; Earnest, Arul; Birden, Hudson; Deaker, Rachelle; Clark, Chris

2008-10-01

This study compared temperature control in different types of vaccine storing refrigerators in general practice and tested knowledge of general practice staff in vaccine storage requirements. Temperature data loggers were set to serially record the temperature within vaccine refrigerators in 28 general practices, recording at 12 minute intervals over a period of 10 days on each occasion. A survey of vaccine storage knowledge and records of divisions of general practice immunisation contacts were also obtained. There was a significant relationship between type of refrigerator and optimal temperature, with the odds ratio for bar style refrigerator being 0.005 (95% CI: 0.001-0.044) compared to the purpose built vaccine refrigerators. Score on a survey of vaccine storage was also positively associated with optimal storage temperature. General practices that invest in purpose built vaccine refrigerators will achieve standards of vaccine cold chain maintenance significantly more reliably than can be achieved through regular cold chain monitoring and practice supports.

A thermostable messenger RNA based vaccine against rabies.

PubMed

Stitz, Lothar; Vogel, Annette; Schnee, Margit; Voss, Daniel; Rauch, Susanne; Mutzke, Thorsten; Ketterer, Thomas; Kramps, Thomas; Petsch, Benjamin

2017-12-01

Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. Most of these cases occur in developing countries, where these vaccines are not available. The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G). Prolonged storage of the vaccine from -80°C to up to +70°C for several months did not impact the protective capacity of the mRNA vaccine. Efficacy after storage was demonstrated by the induction of rabies specific virus neutralizing antibodies and protection in mice against lethal rabies infection. Moreover, storing the vaccine at oscillating temperatures between +4° and +56°C for 20 cycles in order to simulate interruptions of the cold chain during vaccine transport, did not affect the vaccine's immunogenicity and protective characteristics, indicating that maintenance of a cold chain is not essential for this vaccine.

Long-Term Outcomes of Adding HPV Vaccine to the Anal Intraepithelial Neoplasia Treatment Regimen in HIV-Positive Men Who Have Sex With Men

PubMed Central

Deshmukh, Ashish A.; Chhatwal, Jagpreet; Chiao, Elizabeth Y.; Nyitray, Alan G.; Das, Prajnan; Cantor, Scott B.

2015-01-01

Background. Recent evidence shows that quadrivalent human papillomavirus (qHPV) vaccination in men who have sex with men (MSM) who have a history of high-grade anal intraepithelial neoplasia (HGAIN) was associated with a 50% reduction in the risk of recurrent HGAIN. We evaluated the long-term clinical and economic outcomes of adding the qHPV vaccine to the treatment regimen for HGAIN in human immunodeficiency virus (HIV)–positive MSM aged ≥27 years. Methods. We constructed a Markov model based on anal histology in HIV-positive MSM comparing qHPV vaccination with no vaccination after treatment for HGAIN, the current practice. The model parameters, including baseline prevalence, disease transitions, costs, and utilities, were either obtained from the literature or calibrated using a natural history model of anal carcinogenesis. The model outputs included lifetime costs, quality-adjusted life years, and lifetime risk of developing anal cancer. We estimated the incremental cost-effectiveness ratio of qHPV vaccination compared to no qHPV vaccination and decrease in lifetime risk of anal cancer. We also conducted deterministic and probabilistic sensitivity analyses to evaluate the robustness of the results. Results. Use of qHPV vaccination after treatment for HGAIN decreased the lifetime risk of anal cancer by 63% compared with no vaccination. The qHPV vaccination strategy was cost saving; it decreased lifetime costs by $419 and increased quality-adjusted life years by 0.16. Results were robust to the sensitivity analysis. Conclusions. Vaccinating HIV-positive MSM aged ≥27 years with qHPV vaccine after treatment for HGAIN is a cost-saving strategy. Therefore, expansion of current vaccination guidelines to include this population should be a high priority. PMID:26223993

The value of duck-embryo vaccine and high-egg-passage Flury vaccine in experimental rabies infection in guinea-pigs

PubMed Central

Veeraraghavan, N.; Subrahmanyan, T. P.

1963-01-01

The authors have compared the value of multiple doses of duck-embryo and HEP Flury vaccine with that of pooled 5% sheep-brain vaccine in experimental rabies infection in guinea-pigs. They found that the duck-embryo vaccine given in a dosage corresponding to 14 ml of 10% vaccine (the dosage recommended for human treatment), either alone or with antirabies serum, gave no protection and that, even when administered in a dosage corresponding to 140 ml of 5% pooled vaccine, both the duck-embryo and the HEP Flury vaccines, whether alone or with serum, conferred little protection. Pooled phenolized vaccine under identical conditions gave good results. The immunogenicity of duck-embryo and HEP Flury vaccines, given before infection, was also inferior to that of pooled vaccine; and the duck-embryo vaccine was found to be a poorer antigen than the pooled vaccine in mouse potency tests. The authors conclude that the dosage of duck-embryo vaccine recommended for human treatment is inadequate and that the HEP Flury vaccine in its present form is unsuitable for post-infection treatment. PMID:14065070

Evaluation of tumour vaccine immunotherapy for the treatment of advanced non-small cell lung cancer: a systematic meta-analysis.

PubMed

Wang, Min; Cao, Jun-Xia; Liu, Yi-Shan; Xu, Bei-Lei; Li, Duo; Zhang, Xiao-Yan; Li, Jun-Li; Liu, Jin-Long; Wang, Hai-Bo; Wang, Zheng-Xu

2015-04-14

Our meta-analysis performed a systematic evaluation on the therapeutic efficacy and safety of tumour vaccines for the treatment of advanced non-small cell lung cancer (NSCLC). Systematic review and meta-analysis of randomised controlled trials (RCT). PubMed, the Cochrane Center Register of Controlled Trials, Science Direct and EMBASE were searched from January 1980 until January 2015. RCT were included; the control arm had to receive either placebo or chemotherapy or no treatment. The quality of the data from individual papers was assessed for overall survival (OS), clinical response rate and side effects. Overall, 11 RCT of advanced NSCLC with a total of 3986 patients were conducted for meta-analysis. The results showed that the vaccine arm significantly extended primary endpoint median overall survival compared with control group (p<0.00001) (HR 0.760; 95% CI 0.644 to 0.896; p=0.001). Three subgroup patients with tumour vaccine at 1-year, 2-year and 3-year survival rates also gained significant benefits compared with their corresponding control group (p=0.0004, 0.03 and 0.19, respectively). Besides, a significant improvement in median time to progression (TTP), median progression-free survival (PFS) and a trend of improvement in objective response rate were observed after tumour vaccine treatment (p=0.001, 0.005 and 0.05, respectively; median PFS HR 0.842; 95% CI 0.744 to 0.954; p=0.007). A few severe adverse effects occurred in the tumour vaccine group, but fewer side effects were observed in the vaccine group compared with the control group (p<0.00001). Taken together, NSCLC tumour vaccines markedly prolong median OS (p<0.00001), median TTP (p=0.001) and median PFS (p=0.005), improve clinical response rate (p=0.05) and lessen adverse side effects (p<0.00001). Our meta-analysis suggests tumour vaccines improve the efficacy of the treatment, and also provide superiority in treatment of patients with advanced NSCLC among a variety of immunotherapy strategies

Establishing and maintaining the National Vaccination Register in Finland.

PubMed

Baum, Ulrike; Sundman, Jonas; Jääskeläinen, Susanna; Nohynek, Hanna; Puumalainen, Taneli; Jokinen, Jukka

2017-04-27

Computerised, population-based vaccination registers are valuable tools for assessing the vaccine uptake and impact in populations. However, reliable impact assessment is only possible if the data quality can be reviewed and monitored continuously. This report describes the establishment and maintenance of the National Vaccination Register (NVR) in Finland. Currently, the NVR covers nationwide records of vaccinations given within the frame of the National Vaccination Programme since 2009. All vaccinations registered in the NVR contain a record of the personal identity code, the administered vaccine, and the date of vaccination. The vaccine lot number is the key component for recording and identifying vaccinations, because of its broad availability across patient information systems and its importance in vaccine safety monitoring. Vaccination records are accumulated and updated daily into the NVR, and their completeness is monitored monthly to assess deficiencies in data entry and data collection. Additionally, an alert system reports unexpected changes in data accumulation prompting the validation of observed changes in vaccination coverage. The presented process documentation may serve as basis to improve the design and quality of other vaccination or healthcare registers and aims to inspire the set-up of vaccination registers in those countries which still do not have one. This article is copyright of The Authors, 2017.

Vaccine development for syphilis.

PubMed

Lithgow, Karen V; Cameron, Caroline E

2017-01-01

Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a globally prevalent disease despite remaining susceptible to penicillin treatment. Syphilis vaccine development is a viable preventative approach that will serve to complement public health-oriented syphilis prevention, screening and treatment initiatives to deliver a two-pronged approach to stemming disease spread worldwide. Areas covered: This article provides an overview of the need for development of a syphilis vaccine, summarizes significant information that has been garnered from prior syphilis vaccine studies, discusses the critical aspects of infection that would have to be targeted by a syphilis vaccine, and presents the current understanding within the field of the correlates of protection needed to be achieved through vaccination. Expert commentary: Syphilis vaccine development should be considered a priority by industry, regulatory and funding agencies, and should be appropriately promoted and supported.

The Potential Impact of a Hepatitis C Vaccine for People Who Inject Drugs: Is a Vaccine Needed in the Age of Direct-Acting Antivirals?

PubMed Central

Stone, Jack; Martin, Natasha K.; Hickman, Matthew; Hellard, Margaret; Scott, Nick; McBryde, Emma; Drummer, Heidi; Vickerman, Peter

2016-01-01

Background and Aims The advent of highly effective hepatitis C (HCV) treatments has questioned the need for a vaccine to control HCV amongst people who inject drugs (PWID). However, high treatment costs and ongoing reinfection risk suggest it could still play a role. We compared the impact of HCV vaccination amongst PWID against providing HCV treatment. Methods Dynamic HCV vaccination and treatment models among PWID were used to determine the vaccination and treatment rates required to reduce chronic HCV prevalence or incidence in the UK over 20 or 40 years. Projections considered a low (50% protection for 5 years), moderate (70% protection for 10 years) or high (90% protection for 20 years) efficacy vaccine. Sensitivities to various parameters were examined. Results To halve chronic HCV prevalence over 40 years, the low, moderate and high efficacy vaccines required annual vaccination rates (coverage after 20 years) of 162 (72%), 77 (56%) and 44 (38%) per 1000 PWID, respectively. These vaccination rates were 16, 7.6 and 4.4 times greater than corresponding treatment rates. To halve prevalence over 20 years nearly doubled these vaccination rates (moderate and high efficacy vaccines only) and the vaccination-to-treatment ratio increased by 20%. For all scenarios considered, required annual vaccination rates and vaccination-to-treatment ratios were at least a third lower to reduce incidence than prevalence. Baseline HCV prevalence had little effect on the vaccine’s impact on prevalence or incidence, but substantially affected the vaccination-to-treatment ratios. Behavioural risk heterogeneity only had an effect if we assumed no transitions between high and low risk states and vaccinations were targeted or if PWID were high risk for their first year. Conclusions Achievable coverage levels of a low efficacy prophylactic HCV vaccine could greatly reduce HCV transmission amongst PWID. Current high treatment costs ensure vaccination could still be an important

Long-term survival of high-risk melanoma patients immunized with a Hyper-IL-6-modified allogeneic whole-cell vaccine after complete resection.

PubMed

Mackiewicz, Andrzej; Mackiewicz, Jacek; Wysocki, Piotr J; Wiznerowicz, Maciej; Kapcinska, Malgorzata; Laciak, Maria; Rose-John, Stefan; Izycki, Dariusz; Burzykowski, Tomasz; Karczewska-Dzionk, Aldona

2012-06-01

Two single arm, Phase II trials (3 and 5) were undertaken to determine the efficacy and toxicity of an adjuvant treatment using Hyper-IL-6 gene-modified whole-cell allogeneic melanoma vaccine in patients with stage IIIB-IV resected disease. Ninety-seven and 99 patients were enrolled into Trials 3 and 5, respectively. The primary endpoint was disease-free survival (DFS), and the secondary was overall survival (OS). Vaccine was administered eight times every 2 weeks (induction), every month (maintenance) until patient's death. At progression, maintenance was continued or induction was repeated followed by maintenance. Median follow-up was 10.5 and 6.2 years for Trials 3 and 5, respectively. No grade 3 or 4 toxicities were observed. An extension of DFS and OS was observed, when compared with historical non-treated controls. DFS probability at 5 years for Trials 3 and 5 was, respectively, 54.8% and 40.6% for stage IIIB, 25.0% and 24.0% for IIIC, and 8.5% and 17.7% for IV. OS probability at 5 years was, respectively, 66.7% and 56.3% for IIIB, 43.8% and 39.8% for IIIC, and 26.1% and 41.2% for IV. Continuous vaccination, regardless of the disease progression, re-induction, and immunization of patients until death resulted in patients a long-term survival.

Footrot vaccines and vaccination.

PubMed

Dhungyel, Om; Hunter, James; Whittington, Richard

2014-05-30

Research on footrot in small ruminants, which is caused by Dichelobacter nodosus, has led to development of vaccines and their application for control, treatment and eradication of the disease in sheep. Footrot vaccines have evolved over decades to contain monovalent whole cell, multivalent recombinant fimbrial, and finally mono or bivalent recombinant fimbrial antigens. Initially whole cell vaccines made against the few known serogroups of D. nodosus were found to be inefficient in control of the disease in the field, which was attributed to the presence of other unidentified serogroups and also the use of inefficient adjuvants. Fimbriae or pili, which are the basis for antigenic variation, were found to be the major protective and also curative antigens but they are not cross protective between the different serogroups. Multivalent vaccines incorporating all the known serogroups have been proven to be of limited efficacy due to the phenomenon of antigenic competition. Recent studies in Nepal, Bhutan and Australia have shown that outbreak-specific vaccination which involves targeting identified serogroups with mono- or bivalent recombinant fimbrial vaccines, can be very effective in sheep and goats. Where multiple serogroups are present in a flock, antigenic competition can be overcome by sequentially targeting the serogroups with different bivalent vaccines every 3 months. A common antigen which would confer immunity to all serogroups would be the ideal immunogen but the initial studies were not successful in this area. Until universal antigen/s are available, flock specific mono or bivalent fimbrial vaccines are likely to be the most effective tool for control and eradication of footrot in sheep and goats. Future research in footrot vaccines should be focused on improving the duration of prophylaxis by incorporating new and emerging immunomodulators or adjuvants with modified delivery vehicles, discovering a common antigen and understanding the mechanisms of

Designing Peptide-Based HIV Vaccine for Chinese

PubMed Central

Fan, Xiaojuan

2014-01-01

CD4+ T cells are central to the induction and maintenance of CD8+ T cell and antibody-producing B cell responses, and the latter are essential for the protection against disease in subjects with HIV infection. How to elicit HIV-specific CD4+ T cell responses in a given population using vaccines is one of the major areas of current HIV vaccine research. To design vaccine that targets specifically Chinese, we assembled a database that is comprised of sequences from 821 Chinese HIV isolates and 46 human leukocyte antigen (HLA) DR alleles identified in Chinese population. We then predicted 20 potential HIV epitopes using bioinformatics approaches. The combination of these 20 epitopes has a theoretical coverage of 98.1% of the population for both the prevalent HIV genotypes and also Chinese HLA-DR types. We suggest that testing this vaccine experimentally will facilitate the development of a CD4+ T cell vaccine especially catered for Chinese. PMID:25136573

Designing peptide-based HIV vaccine for Chinese.

PubMed

Shu, Jiayi; Fan, Xiaojuan; Ping, Jie; Jin, Xia; Hao, Pei

2014-01-01

CD4+ T cells are central to the induction and maintenance of CD8+ T cell and antibody-producing B cell responses, and the latter are essential for the protection against disease in subjects with HIV infection. How to elicit HIV-specific CD4+ T cell responses in a given population using vaccines is one of the major areas of current HIV vaccine research. To design vaccine that targets specifically Chinese, we assembled a database that is comprised of sequences from 821 Chinese HIV isolates and 46 human leukocyte antigen (HLA) DR alleles identified in Chinese population. We then predicted 20 potential HIV epitopes using bioinformatics approaches. The combination of these 20 epitopes has a theoretical coverage of 98.1% of the population for both the prevalent HIV genotypes and also Chinese HLA-DR types. We suggest that testing this vaccine experimentally will facilitate the development of a CD4+ T cell vaccine especially catered for Chinese.

Economic comparison of common treatment protocols and J5 vaccination for clinical mastitis in dairy herds using optimized culling decisions.

PubMed

Kessels, J A; Cha, E; Johnson, S K; Welcome, F L; Kristensen, A R; Gröhn, Y T

2016-05-01

This study used an existing dynamic optimization model to compare costs of common treatment protocols and J5 vaccination for clinical mastitis in US dairy herds. Clinical mastitis is an infection of the mammary gland causing major economic losses in dairy herds due to reduced milk production, reduced conception, and increased risk of mortality and culling for infected cows. Treatment protocols were developed to reflect common practices in dairy herds. These included targeted therapy following pathogen identification, and therapy without pathogen identification using a broad-spectrum antimicrobial or treating with the cheapest treatment option. The cost-benefit of J5 vaccination was also estimated. Effects of treatment were accounted for as changes in treatment costs, milk loss due to mastitis, milk discarded due to treatment, and mortality. Following ineffective treatments, secondary decisions included extending the current treatment, alternative treatment, discontinuing treatment, and pathogen identification followed by recommended treatment. Average net returns for treatment protocols and vaccination were generated using an existing dynamic programming model. This model incorporates cow and pathogen characteristics to optimize management decisions to treat, inseminate, or cull cows. Of the treatment protocols where 100% of cows received recommended treatment, pathogen-specific identification followed by recommended therapy yielded the highest average net returns per cow per year. Out of all treatment scenarios, the highest net returns were achieved with selecting the cheapest treatment option and discontinuing treatment, or alternate treatment with a similar spectrum therapy; however, this may not account for the full consequences of giving nonrecommended therapies to cows with clinical mastitis. Vaccination increased average net returns in all scenarios. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Vaccine development for syphilis

PubMed Central

Lithgow, Karen V.

2017-01-01

Introduction Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a globally prevalent disease despite remaining susceptible to penicillin treatment. Syphilis vaccine development is a viable preventative approach that will serve to complement public health-oriented syphilis prevention, screening and treatment initiatives to deliver a two-pronged approach to stemming disease spread worldwide. Areas covered This article provides an overview of the need for development of a syphilis vaccine, summarizes significant information that has been garnered from prior syphilis vaccine studies, discusses the critical aspects of infection that would have to be targeted by a syphilis vaccine, and presents the current understanding within the field of the correlates of protection needed to be achieved through vaccination. Expert commentary Syphilis vaccine development should be considered a priority by industry, regulatory and funding agencies, and should be appropriately promoted and supported. PMID:27328030

The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta.

PubMed

Biggin, Andrew; Zheng, Linda; Briody, Julie N; Coorey, Craig P; Munns, Craig F

2015-01-01

Intravenous bisphosphonate therapy is the first-line treatment in moderate-to-severe osteogenesis imperfecta (OI), but there are varied treatment protocols with little data on long-term efficacy. This study evaluates the clinical outcomes when transitioning from active bisphosphonate treatment to maintenance therapy. A retrospective review was conducted on 17 patients before treatment, following active treatment (zoledronate 0.05 mg/kg 6-monthly or pamidronate 6-9 mg/kg/year) and after establishment on maintenance treatment for more than 2 years (zoledronate 0.025 mg/kg 6-monthly or pamidronate <4 mg/kg/year). There was a significant reduction in mean fracture rate from 1.5 ± 1.1 fractures/year at baseline to 0.7 ± 0.7 fractures/year on active treatment. Z-scores for lumbar spine bone mineral density, bone mineral content, volumetric bone mineral density and bone mineral content for lean tissue mass increased during active treatment. These improvements were maintained during the period of maintenance treatment. Vertebral height improved in fractured thoracic vertebrae from pre-treatment to active therapy and improved further during maintenance treatment. Metacarpal cortical thickness and relative cortical area also increased over the treatment periods. Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of active treatment at the doses stated above. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI. © 2015 S. Karger AG, Basel.

Association between gene variants and response to buprenorphine maintenance treatment.

PubMed

Gerra, Gilberto; Somaini, Lorenzo; Leonardi, Claudio; Cortese, Elena; Maremmani, Icro; Manfredini, Matteo; Donnini, Claudia

2014-01-30

A variety of studies were addressed to differentiate responders and non-responders to substitution treatment among heroin dependent patients, without conclusive findings. In particular, preliminary pharmacogenetic findings have been reported to predict treatment effectiveness in mental health and substance use disorders. Aim of the present study was to investigate the possible association of buprenorphine (BUP) treatment outcome with gene variants that may affect kappa-opioid receptors and dopamine system function. One hundred and seven heroin addicts (West European, Caucasians) who underwent buprenorphine maintenance treatment were genotyped and classified into two groups (A and B) on the basis of treatment outcome. Non-responders to buprenorphine (group B) have been identified taking into account early drop out, continuous use of heroin, severe behavioral or psychiatric problems, misbehavior and diversion during the 6 months treatment period. No difference was evidenced between responders and non-responders to BUP in the frequency of kappa opioid receptor (OPRK1) 36G>T SNP. The frequency of dopamine transporter (DAT) gene polymorphism (SLC6A3/DAT1), allele 10, was evidently much higher in "non-responder" than in "responder" individuals (64.9% vs. 55.93%) whereas the frequency of the category of other alleles (6, 7 and 11) was higher in responder than in non-responder individuals (11.02% vs. 2.13% respectively). On one hand, the hypothesis that possible gene-related changes in kappa-opioid receptor could consistently affect buprenorphine pharmacological action and clinical effectiveness was not confirmed in our study, at least in relation to the single nucleotide polymorphism 36G>T. On the other hand, the possibility that gene-related dopamine changes could have reduced BUP effectiveness and impaired maintenance treatment outcome was cautiously supported by our findings. DAT1 gene variants such as allele 10, previously reported in association with personality and

A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

PubMed Central

GORDON, MICHAEL S.; KINLOCK, TIMOTHY W.; COUVILLION, KATHRYN A.; SCHWARTZ, ROBERT P.; O’GRADY, KEVIN

2014-01-01

The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly assigned to one of three treatment conditions: counseling only (counseling in prison; n= 70); counseling plus transfer (counseling in prison with transfer to methadone maintenance treatment upon release; n= 70); and counseling plus methadone (methadone maintenance in prison, continued in a community-based methadone maintenance program upon release; n= 71). Entered prison treatment (p <. 01), and completed prison treatment (p< .001) were significantly predicted by the set of 10 explanatory variables and favored the treatment conditions receiving methadone. The present results indicate that individuals who are older in age and have longer prison sentences may have better outcomes than younger individuals with shorter sentences, meaning they are more likely to enter and complete prison-based treatment. Furthermore, implications for the treatment of prisoners with prior heroin dependence and for conducting clinical trials may indicate the importance of examining individual characteristics and the possibility of the examination of patient preference. PMID:25392605

A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison.

PubMed

Gordon, Michael S; Kinlock, Timothy W; Couvillion, Kathryn A; Schwartz, Robert P; O'Grady, Kevin

2012-05-01

The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly assigned to one of three treatment conditions: counseling only (counseling in prison; n= 70); counseling plus transfer (counseling in prison with transfer to methadone maintenance treatment upon release; n= 70); and counseling plus methadone (methadone maintenance in prison, continued in a community-based methadone maintenance program upon release; n= 71). Entered prison treatment (p <. 01), and completed prison treatment (p< .001) were significantly predicted by the set of 10 explanatory variables and favored the treatment conditions receiving methadone. The present results indicate that individuals who are older in age and have longer prison sentences may have better outcomes than younger individuals with shorter sentences, meaning they are more likely to enter and complete prison-based treatment. Furthermore, implications for the treatment of prisoners with prior heroin dependence and for conducting clinical trials may indicate the importance of examining individual characteristics and the possibility of the examination of patient preference.

Efficacité de la gestion de vaccins et qualité de vaccination à l'antenne PEV Kisangani en République Démocratique du Congo

PubMed Central

Labama, Matthieu Betofe; Longembe, Eugène Basandja; Likwela, Joris Losimba

2017-01-01

Introduction La qualité des vaccins conditionne les résultats attendus de la vaccination. Elle est tributaire de l'efficacité de système de gestion technique et logistique mis en place. Cette étude est menée pour évaluer l'efficacité de la gestion des vaccins et d'en tirer des leçons. Méthodes Une étude rétrospective est menée pendant la période de 2010 à 2014 sur la gestion logistique de vaccins au niveau de l'antenne PEV Kisangani. La revue documentaire complétée par les entretiens semi-dirigés des gestionnaires et prestataires de services de vaccination ont permis d'évaluer la gestion de vaccins en se servant des modèle GEV de l'OMS, en vue de dégager les écarts. Résultats Il est observé une faible connaissance des prestataires sur les vaccins qui ne peuvent pas être congelés, sur les tests de congélation et d'autres dommages de vaccins. La gestion informatisée des données au niveau de l'antenne est correctement assurée. Aucun critère évalué n'a atteint l'objectif de 80%. Le respect de la température de stockage est de 70% au niveau de l'antenne ; le critère relatif à la gestion de vaccins est respectivement de 65% et 67% au niveau du BCZ et CS. Le critère relatif à la maintenance est nul à tous les niveaux. Conclusion Le dysfonctionnement de système logistique est remarquable à tous les niveaux de la pyramide sanitaire, ceci pourrait interférer avec la qualité et l'impact attendu de la vaccination. Une attention particulière doit être accordée à la maintenance des équipements. PMID:28748006

Vaccinating Patients With Inflammatory Bowel Disease

PubMed Central

Reich, Jason; Wasan, Sharmeel

2016-01-01

Patients with inflammatory bowel disease (IBD) are not vaccinated at the same rate as general medical patients. IBD places patients at increased risk for developing vaccine-preventable illnesses, and this risk is further exacerbated by immunosuppressive therapy. Therefore, gastroenterologists should familiarize themselves with health maintenance measures pertaining to patients with IBD. This article highlights the vaccinations required for patients with IBD, especially those who are immunosuppressed: influenza; pneumococcal pneumonia; hepatitis A and B viruses; human papilloma virus; meningococcal disease; tetanus, diphtheria, and pertussis; measles, mumps, and rubella; varicella zoster; and herpes zoster. This article also discusses issues regarding patients with IBD who travel outside of the United States, as well as highlights and provides suggestions for areas of quality improvement that are needed in the field. PMID:27917091

Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine.

PubMed

Nagel, J; Saxne, T; Geborek, P; Bengtsson, A A; Jacobsen, S; Svaerke Joergensen, C; Nilsson, J-Å; Skattum, L; Jönsen, A; Kapetanovic, M C

2017-09-01

Background/purpose The objective of this study was to explore the impact of systemic lupus erythematosus and belimumab given in addition to standard of care therapy on 13-valent conjugated pneumococcal vaccine (PCV13) response. Methods Forty-seven systemic lupus erythematosus patients and 21 healthy controls were immunized with a single dose of 13-valent conjugated pneumococcal vaccine. Forty systemic lupus erythematosus patients were treated with traditional disease-modifying anti rheumatic drugs, 11 of those received belimumab in addition, and 32 patients were treated with concomitant prednisolone. Quantification of serotype specific IgG levels to 12 pneumococcal capsular polysaccharides was performed in serum taken before and four to six weeks after vaccination using multiplex fluorescent microsphere immunoassay. IgG levels against serotypes 23F and 6B were also analyzed using standard enzyme-linked immunosorbent assays. Opsonophagocytic assay was performed on serotype 23F to evaluate the functionality of the antibodies. Pre- and post-vaccination log transformed antibody levels were compared to determine the impact of systemic lupus erythematosus diagnosis and different treatments on antibody response. Results Systemic lupus erythematosus patients as a group showed lower post-vaccination antibody levels and lower fold increase of antibody levels after vaccination compared to controls ( p = 0.02 and p = 0.009, respectively). Systemic lupus erythematosus patients treated with belimumab in addition to standard of care therapy or with only hydroxychloroquine did not differ compared to controls, whereas the other treatment groups had significantly lower fold increase of post-vaccination antibody levels. Higher age was associated with lower post-vaccination antibody levels among systemic lupus erythematosus patients. Conclusion Belimumab given in addition to traditional disease-modifying anti rheumatic drugs or prednisolone did not further impair antibody

Beyond new vaccine introduction: the uptake of pneumococcal conjugate vaccine in the African Region.

PubMed

Olayinka, Folake; Ewald, Leah; Steinglass, Robert

2017-01-01

The number of vaccines available to low-income countries has increased dramatically over the last decade. Overall infant immunization coverage in the WHO African region has stagnated in the past few years while countries' ability to maintain high immunization coverage rates following introduction of new vaccines has been uneven. This case study examines post-introduction coverage among African countries that introduced PCV between 2008 and 2013 and the factors affecting Pneumococcal Conjugate Vaccine (PCV) introduction. Nearly one-third of countries did not achieve 80% infant PCV3 coverage by two years post-introduction and 58% of countries experienced a decline in coverage between post introduction years two and four. Major factors affecting coverage rates included introduction without adequate preparation, insufficient supply chain capacity and management, poor communication between organizations and with the public, and data collection systems that were insufficient to meet information needs. Deliberately addressing these issues as well as longstanding weaknesses during new vaccine introduction can strengthen the immunization and broader health system. Further study is required to identify and address factors that affect maintenance of high coverage following introduction of new vaccines in the African region. Immunization with PCV is one of the most important interventions protecting against pneumonia, the second leading cause of death for children under five globally.

The Human Papillomavirus Vaccine: Current Perspective and Future Role in Prevention and Treatment of Anal Intraepithelial Neoplasia and Anal Cancer

PubMed Central

Mehta, Mudresh R.; Lewis, James S.; Lockhart, A. Craig

2016-01-01

The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are rising in the U.S. and globally. Five-year survival rates with current modalities of treatment for anal cancer are generally favorable for localized and regional disease. For metastatic disease, the relative survival rate is poor. Major contributing factors for the increase in anal cancer incidence include increasing receptive anal intercourse (hetero- and homosexual), increasing HPV infections, and longer life expectancy of treated people who are seropositive for human immunodeficiency virus. Because treatment outcomes with systemic therapy in patients with advanced disease are so poor, prevention may be the best approach for reducing disease burden. The association of a major causative agent with anal cancer provides an excellent opportunity for prevention and treatment. The advent of the HPV vaccine for anal cancer prevention and treatment is a significant milestone and has the potential to greatly impact these cancers. The data regarding potential use of the HPV vaccine in anal cancer prevention and treatment are reviewed. Implications for Practice: The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are on the rise in the U.S. and globally. Based on recent studies, the HPV vaccine is approved for prevention of the infection and development of HPV-related anal cancer. In addition, several small studies have shown that the vaccine may be useful as adjuvant therapy for anal cancer. There is a need for public health strategies aimed at education of both patients and practitioners to improve the use of the vaccine for prevention of HPV-related anal cancer. The development of a therapeutic vaccine is a work in progress. PMID:26961923

Renewed behavior produced by context change and its implications for treatment maintenance: A review.

PubMed

Podlesnik, Christopher A; Kelley, Michael E; Jimenez-Gomez, Corina; Bouton, Mark E

2017-07-01

Behavioral treatment gains established in one setting do not always maintain in other settings. The present review examines the relevance of basic and translational research to understanding failures to maintain treatment gains across settings. Specifically, studies of the renewal effect examine how transitioning away from a treatment setting could evoke a return of undesirable behavior, rather than newly trained appropriate behavior. Studies of renewal typically arrange three phases, with a response trained and reinforced under a particular set of contextual stimuli in the first phase. Next, that response is extinguished, often under a different set of contextual stimuli. Finally, that response returns despite extinction remaining in effect upon returning to the original training context or transitioning to a novel context. Thus, removing the extinction context is sufficient to produce a recurrence of the response. The findings suggest treatment effects can become specific to the context in which the treatment was delivered. This literature offers promising methods for systematically assessing the factors contributing to treatment maintenance and improving generalization of treatment gains across contexts. Therefore, the present review suggests basic and translational research on renewal provides an empirical literature to bring greater conceptual systematization to understanding generalization and maintenance of behavioral treatment. © 2017 Society for the Experimental Analysis of Behavior.

Impact of anti-rheumatic treatment on immunogenicity of pandemic H1N1 influenza vaccine in patients with arthritis.

PubMed

Kapetanovic, Meliha C; Kristensen, Lars-Erik; Saxne, Tore; Aktas, Teodora; Mörner, Andreas; Geborek, Pierre

2014-01-02

An adjuvanted pandemic H1N1 influenza (pH1N1) vaccine (Pandemrix) was reported as highly immunogenic resulting in seroconversion in 77 to 94% of adults after administration of a single dose. The aim of the study was to investigate the impact of different anti-rheumatic treatments on antibody response to pH1N1 vaccination in patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA). Patients with arthritis (n = 291; mean age 57 years, 64% women) participated. Hemagglutination inhibition (HI) assay was performed on blood samples drawn before and after a mean (SD) of 8.3 (4) months following vaccination. A positive immune response i.e. seroconversion was defined as negative prevaccination serum and postvaccination HI titer ≥40 or a ≥4-fold increase in HI titer. All patients were divided into predefined groups based on diagnosis (RA or SpA) and ongoing treatment: methotrexate (MTX), anti-tumor necrosis factor (anti-TNF) as monotherapy, MTX combined with anti-TNF, other biologics (abatacept, rituximab, tocilizumab) and non-steroidal anti-inflammatory drugs (NSAIDs)/analgesics. Predictors of positive immune response were studied using logistic regression analysis. The percentage of patients with positive immune response in the different treatment groups was: 1. RA on MTX 42%; 2. RA on anti-TNF monotherapy 53%; 3. RA on anti-TNF + MTX 43%; 4. RA on other biologics (abatacept 20%, rituximab 10% and tocilizumab 50%); 5. SpA on anti-TNF monotherapy 76%; 6. SpA on anti-TNF + MTX 47%; and 7. SpA on NSAIDs/analgesics 59%. RA patients on rituximab had significantly lower (P < 0.001) and SpA on anti-TNF monotherapy significantly better response rates compared to other treatment groups (P 0.001 to 0.033). Higher age (P < 0.001) predicted impaired immune response. Antibody titers 3 to 6 months after vaccination was generally lower compared to those within the first 3 months but no further decrease in titers were observed 6 to 22 months after

Vaccine therapy for HIV: a historical review of the treatment of infectious diseases by active specific immunization with microbe-derived antigens.

PubMed

Burke, D S

1993-01-01

A review of the history of 'vaccine therapy' for infectious diseases is presented. The concept originated when Auzias-Turenne introduced 'syphilitic vaccination' or 'syphilization' as a treatment for syphilis in Paris in the mid-1800s; his clinical studies probably influenced Pasteur's successful rabies postexposure vaccine trials. Robert Koch in Berlin in the 1890s observed that inoculation of tuberculin into patients with tuberculosis induced an inflammatory response in affected tissues, and advocated 'tuberculin therapy'. Sir Almroth Wright in London in the early 20th century devised methods to measure changes in serum 'opsonizing' activity in response to therapeutic inoculations with microbe-derived vaccines. Since the advent of antibiotics, active specific immunization with microbe-derived antigens (vaccine therapy) has been largely forgotten as a strategy for treatment of infectious diseases. Advances in antigen production and in molecular immunology now permit new tactics to probe, analyse and selectively alter in vivo human immune responses to infectious microbes. Our recent demonstration that vaccine therapy can boost natural immunity to HIV in infected patients should rekindle interest in this approach.

Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial.

PubMed

Berk, Michael; Dean, Olivia M; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Moss, Kirsteen; Allwang, Christine; Schapkaitz, Ian; Cobb, Heidi; Bush, Ashley I; Dodd, Seetal; Malhi, Gin S

2012-08-14

N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

Efficacy of influenza vaccination and tamiflu® treatment--comparative studies with Eurasian Swine influenza viruses in pigs.

PubMed

Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

2013-01-01

Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.

Vaccines for leishmaniasis: from proteome to vaccine candidates.

PubMed

Schroeder, Juliane; Aebischer, Toni

2011-01-01

Leishmania spp. cause a wide spectrum of tropical diseases which are threatening an estimated 350 million people around the globe. While in most cases non-fatal, the disease is associated with high morbidity, social stigmata and poverty. However, the most severe form visceral leishmaniasis can be fatal if left untreated. Chemotherapeutics are available but show high toxicity, costs and are prone to resistance development due to prolonged treatment periods. Healing is associated with a life-long resistance to re-infection and this argues for the feasibility of vaccination. However, despite much effort, no such vaccine has become available yet. Here, the status of vaccine development in this field is briefly summarized before the focus is set on the promise of reverse vaccinology for anti-Leishmania vaccine development in the post-genomic era. We report on our own experience with this approach using an instructive example of successful candidate vaccine antigen identification.

Treatment of dogs with lymphoma using a 12-week, maintenance-free combination chemotherapy protocol.

PubMed

Simon, D; Nolte, I; Eberle, N; Abbrederis, N; Killich, M; Hirschberger, J

2006-01-01

Treatment of lymphoma in dogs by long-term chemotherapy has favorable results. However, the efficacy of short-term, maintenance-free treatment protocols on remission and survival times in dogs has not been determined. That treatment using a 12-week chemotherapy protocol would be associated with satisfactory treatment outcome in dogs with lymphoma. 77 dogs with histologically or cytologically confirmed diagnosis of lymphoma. Prospective clinical trial in which dogs were treated with a 12-week chemotherapy protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and prednisolone. Complete remission rate was 76.3%. Multivariate logistic regression analysis revealed that clinical substage (P = .006) and immunophenotype (P = .003) had a significant influence on the likelihood of a dog achieving complete remission. Median duration of first complete remission was 243 days (range 19-1,191 days). The 6-month, 1-year, and 2-year remission rates were 68%, 28%, and 16%, respectively. In the multivariate analysis of patient variables, immunophenotype (P = .022) revealed a significant influence on first remission duration. Toxicosis was mild with the exception of 1 treatment-associated death. In this group of dogs the 12-week maintenance-free chemotherapy protocol was well tolerated and had satisfactory results.

Preventive maintenance study : interim report.

DOT National Transportation Integrated Search

2017-09-01

This interim report details the performance of 69 test sites treated with various preventive maintenance treatments. The maintenance treatments applied included crack sealing, full lane chip sealing, wheel path chip sealing, dig outs (mill and fill),...

Economic analysis of pandemic influenza vaccination strategies in Singapore.

PubMed

Lee, Vernon J; Tok, Mei Yin; Chow, Vincent T; Phua, Kai Hong; Ooi, Eng Eong; Tambyah, Paul A; Chen, Mark I

2009-09-22

All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore. We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling) compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay) depending on the perceived risk of the next pandemic occurring. The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4-0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups. The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines.

Therapeutic HPV vaccines.

PubMed

Hancock, Gemma; Hellner, Karin; Dorrell, Lucy

2018-02-01

High-risk human papillomavirus (HPV) infection is known to be a necessary factor for cervical and anogenital malignancies. Cervical cancers account for over a quarter of a million deaths annually. Despite the availability of prophylactic vaccines, HPV infections remain extremely common worldwide. Furthermore, these vaccines are ineffective at clearing pre-existing infections and associated preinvasive lesions. As cervical dysplasia can regress spontaneously, a therapeutic HPV vaccine that boosts host immunity could have a significant impact on the morbidity and mortality associated with HPV. Therapeutic vaccines differ from prophylactic vaccines in that they are aimed at generating cell-mediated immunity rather than neutralising antibodies. This review will cover various therapeutic vaccine strategies in development for the treatment of HPV-associated lesions and cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Development of Peptide Vaccines for Triple-Negative Breast Cancer Treatment].

PubMed

Toh, Uhi; Saku, Shuko; Okabe, Mina; Iwakuma, Nobutaka; Kimitsuki, Yuko; Akashi, Momoko; Ogo, Etsuyo; Yamada, Akira; Shichijo, Shigeki; Itoh, Kyogo; Akagi, Yoshito

2016-10-01

Our previous phase II clinical trial showed that therapeutically selected personalized peptide vaccines(PPVs)were effective at boosting anticancer immunity; the immune response after PPV was associated with a clinical outcome as a prognostic factor for metastatic breast cancer(mBC). We conducted an early phase II study to evaluate the safety and efficacy of a new regimen using multiple peptide vaccines(KRM-19)for patients with metastatictriple -negative breast cancer. KRM-19 consisted of 19 mixed peptides chosen from the previously reported 31 PPVs according to their anti-tumor immunologiceffec ts and safety profiles for patients with mBC. All patients had histologically confirmed measurable ER-PgR-HER2- mBC and their human leukocyte antigen(HLA) / -A molecules were A2, A3, A11, A24, A26, A31, or A33. KRM-19(19mg/mL)was administrated subcutaneously every week for a total of 6 doses. Concurrent conventional chemo- and/or endocrine therapy were not permitted during treatment. This was an open-label, early phase II study. The primary endpoint was safety and anti-tumor immunologic effect, while the secondary endpoints were clinical responses and progression-free survival(PFS). The estimated enrollment was 10-15 and 8 patients were enrolled(Clinical trial registry number: UMIN000014616). Measurement of peptide-specific cytotoxic T lymphocyte and IgG responses were conducted before and after vaccination. The correlation between PFS and the increased IgG response and/or CTL levels were investigated.

The Effectiveness of Group Spiritual Intervention on Self-esteem and Happiness among Men Undergoing Methadone Maintenance Treatment.

PubMed

Jalali, Amir; Behrouzi, Mahvash Kashkouli; Salari, Nader; Bazrafshan, Mohammad-Rafi; Rahmati, Mahmoud

2018-05-10

Drug dependence or substance use disorder not only affects a person's life but also brings a lot of challenges for families and communities and imposes heavy burdens on them. There are various therapies in the domain of addiction whose main purposes are to reduce or to cut down substance abuse. This study aimed to determine the effectiveness of group spiritual intervention on self-esteem and happiness among male clients undergoing methadone maintenance treatment. This study was an intervention study in which 60 clients affected with substance abuse and undergoing methadone maintenance treatment were recruited. The study samples were selected through convenience sampling method and then divided randomly into two groups of 30 individuals: intervention and control. The intervention group attended group spiritual interventions for 10 sessions. Self-esteem and happiness among the study participants were also measured through Coopersmith Self-Esteem Inventory and Oxford Happiness Questionnaire before and after the intervention. The results showed a significant difference between both intervention and control groups in terms of self-esteem and happiness (P˂0.05); so that the participants in the intervention group demonstrated a significant improvement in their self-esteem and happiness. It was concluded that group spiritual intervention as a useful method could be effective in enhancing self-esteem and happiness among addicted individuals undergoing methadone maintenance treatment. The given treatment could be also used as a complementary therapy beside methadone maintenance treatment to reduce the likelihood of people returning to substance abuse. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Treatment of canine visceral leishmaniasis by the vaccine Leish-111f+MPL-SE.

PubMed

Trigo, Joelma; Abbehusen, Melissa; Netto, Eduardo M; Nakatani, Maria; Pedral-Sampaio, Geraldo; de Jesus, Robson Silva; Goto, Yasuyuki; Guderian, Jeffrey; Howard, Randall F; Reed, Steven G

2010-04-26

Immunotherapy of canine visceral leishmaniasis (CVL) may provide an alternative to both marginally effective chemotherapy and undesired euthanasia of infected dogs and could have a great impact not only on animal welfare, but also on control of human disease. Therefore, we examined the potential immunotherapeutic efficacy of the subunit vaccine Leish-111f+MPL-SE, which has undergone rigorous preclinical testing and been demonstrated safe in human clinical trials. Two separate trials were performed in Salvador, Brazil, to evaluate the vaccine for therapeutic efficacy against CVL caused by natural infection: an Open Trial and a Blinded Trial. In the Open Trial 59 dogs with clinically active CVL were sequentially allocated to four groups: group 1 received Leish-111f+MPL-SE; group 2 was treated with Glucantime; group 3 received a combination of the vaccine and Glucantime; and group 4 was given no treatment. At the 6-month assessment, the 13 non-treated dogs had either died or showed no clinical improvement. In contrast, most dogs in groups 1-3 showed initial improvement (100%, 80%, and 92%, respectively). Upon evaluation for a mean of 36 months after therapy, the following cure rates were observed: 75% for group 1 dogs (exact 95% confidence interval [CI] 43-95%), 64% for group 2 dogs (exact 95% CI 31-89%), and 50% for group 3 dogs (exact 95% CI 19-81%). Therapeutic efficacy of the Leish-111f+MPL-SE vaccine was reconfirmed in a subsequent Blinded Trial. The vaccine was effective for mild cases of CVL and was compromised in dogs with severe disease. Although further studies are required to understand mechanisms of action, the Leish-111f+MPL-SE vaccine is a promising tool to control VL in both dogs and humans. Copyright 2010 Elsevier Ltd. All rights reserved.

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

PubMed Central

Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

2016-01-01

Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

Current ebola vaccines.

PubMed

Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz

2012-07-01

Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates (NHPs), with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in NHPs, the gold standard animal model for ebola hemorrhagic fever. This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios and describes current ebolavirus vaccines. Among these vaccines are recombinant adenoviruses, recombinant vesicular stomatitis viruses (VSVs), recombinant human parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant VSVs, has also demonstrated post-exposure protection in NHPs. The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and toward licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible.

42 CFR 2.34 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CONFIDENTIALITY OF ALCOHOL AND DRUG ABUSE PATIENT... means the dispensing of a narcotic drug in decreasing doses to an individual in order to reduce or... narcotic drug. Maintenance treatment means the dispensing of a narcotic drug in the treatment of an...

42 CFR 2.34 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CONFIDENTIALITY OF ALCOHOL AND DRUG ABUSE PATIENT... means the dispensing of a narcotic drug in decreasing doses to an individual in order to reduce or... narcotic drug. Maintenance treatment means the dispensing of a narcotic drug in the treatment of an...

42 CFR 2.34 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CONFIDENTIALITY OF ALCOHOL AND DRUG ABUSE PATIENT... means the dispensing of a narcotic drug in decreasing doses to an individual in order to reduce or... narcotic drug. Maintenance treatment means the dispensing of a narcotic drug in the treatment of an...

42 CFR 2.34 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CONFIDENTIALITY OF ALCOHOL AND DRUG ABUSE PATIENT... means the dispensing of a narcotic drug in decreasing doses to an individual in order to reduce or... narcotic drug. Maintenance treatment means the dispensing of a narcotic drug in the treatment of an...

Long-Term Clinical Response to Treatment and Maintenance of Localized Aggressive Periodontitis: A Cohort Study

PubMed Central

Miller, Karina A. F. S.; Branco-de-Almeida, Luciana S.; Wolf, Sandra; Hovencamp, Nicole; Treloar, Tina; Harrison, Peter; Aukhil, Ikramuddin; Gong, Yan; Shaddox, Luciana M.

2016-01-01

Aim To evaluate long-term clinical response to periodontal therapy and maintenance in localized aggressive periodontitis (LAP). Materials and Methods One hundred forty-one African-Americans diagnosed with LAP, aged 5–25 years, were enrolled. Patients underwent periodontal mechanical debridement plus one week of amoxicillin/metronidazole. Mechanical therapy was repeated as needed and clinical parameters were recorded at baseline, 3, 6, 12, 18, and 24 months, and 2 additional annual follow-up visits after treatment. Radiographs from primary dentition of patients with LAP in permanent dentition, and additional healthy siblings (HS) were analyzed retrospectively. Results Periodontal therapy significantly improved probing depth and clinical attachment level up to 4 years (mean reductions: 2.18 ± 1.03 and 2.80 ± 1.43 mm, respectively). Percentage of affected sites was reduced at all timepoints and maintained up to 4 years. Noncompliance with antibiotics/appointments negatively affected the treatment response. Ninety percent of LAP patients in permanent dentition and 32% of HS presented radiographic bone loss in primary dentition. Conclusions Mechanical debridement with one-week of systemic antibiotics along with proper periodontal maintenance was effective in the treatment and successful maintenance of LAP for up to 4 years. LAP in permanent dentition may be preceded in the primary dentition. Clinicaltrials.gov #NCT01330719. PMID:27767222

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

PubMed Central

2012-01-01

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493). PMID:22891797

Cost benefit analysis of including microsurfacing in pavement treatment strategies & cycle maintenance : executive summary.

DOT National Transportation Integrated Search

2011-01-01

The overall value of using thin surfacing maintenance treatments to extend and preserve the : performance of existing pavements has been widely recognized. This study has focused on : evaluating the cost effectiveness of commonly used individual trea...

Vaccination titres pre- and post-transplant in paediatric renal transplant recipients and the impact of immunosuppressive therapy.

PubMed

Höcker, Britta; Aguilar, Martin; Schnitzler, Paul; Pape, Lars; Bald, Martin; König, Jens; Marks, Stephen D; Genc, Gurkan; Büscher, Anja; Kemper, Markus J; Billing, Heiko; Pohl, Martin; Dello Strologo, Luca; Webb, Nicholas J A; Rieger, Susanne; Mankertz, Annette; Krupka, Kai; Bruckner, Thomas; Fichtner, Alexander; Tönshoff, Burkhard

2018-05-01

Avoidance of vaccine-preventable infections in paediatric renal allograft recipients is of utmost importance. However, the development and maintenance of protective vaccination titres may be impaired in this patient population owing to their need for immunosuppressive medication. In the framework of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN), we therefore performed a multi-centre, multi-national study and analysed vaccination titres pre- and post-transplant in 155 patients with serial titre measurements in comparison with published data in healthy children. The percentage of patients with positive vaccination titres before renal transplantation (RTx) was low, especially for diphtheria (38.5%, control 75%) and pertussis (21.3%, control 96.3%). As few as 58.1% of patients had a hepatitis B antibody (HBsAb) titre >100 IU/L before RTx. 38.1% of patients showed a vaccination titre loss post-transplant. Patients with an HBsAb titre between 10 and 100 IU/L before RTx experienced a significantly (p < 0.05) more frequent hepatitis B vaccination titre loss post-transplant than patients with an HBsAb titre >100 IU/L. The revaccination rate post-transplant was low and revaccination failed to induce positive titres in a considerable number of patients (27.3 to 83.3%). Treatment with rituximab was associated with a significantly increased risk of a vaccination titre loss post-transplant (odds ratio 4.26, p = 0.033). These data show a low percentage of patients with positive vaccination titres pre-transplant, a low revaccination rate post-transplant with limited antibody response, and a high rate of vaccination titre losses.

Hepatitis A vaccines.

PubMed

Nothdurft, Hans Dieter

2008-07-01

The global disease burden associated with hepatitis A virus (HAV) is expected to increase in the coming years due to a shift in the epidemiological pattern of the disease. A decrease in the prevalence of natural immunity is leading to an increased number of adolescents and adults susceptible to a disease that is associated with greater morbidity, mortality and treatment costs in older-age groups. Current HAV vaccines have been shown to be safe, highly immunogenic and confer long-lasting protection against HAV disease. Vaccine-induced antibodies persist for more than 12 years in vaccinated adults and mathematical modeling predicts antibody persistence for more than 25 years in over 95% of vaccine recipients. However, the cost of HAV vaccines has been prohibitive for some countries. Recent studies in countries with transitioning HAV endemicity indicate that the cost-benefit ratio of mass vaccination against HAV would be similar to other routine childhood vaccinations.

A Phase 1 study of Vorinostat Maintenance after Autologous Transplant in High Risk Lymphoma

PubMed Central

Hofmeister, Craig C.; Williams, Nita; Geyer, Susan; Hade, Erinn M.; Bowers, Mindy A.; Earl, Christian T.; Vaughn, John; Bingman, Anissa; Humphries, Kristina; Lozanski, Gerard; Baiocchi, Robert A.; Jaglowski, Samantha M.; Blum, Kristie; Porcu, Pierluigi; Flynn, Joseph; Penza, Sam; Benson, Don M.; Andritsos, Leslie A.; Devine, Steven M.

2014-01-01

Only a minority of patients with high risk lymphoma will be cured with autologous transplant, so maintenance with Vorinostat, an oral agent with activity in relapsed lymphoma, was studied starting day +60 for 21 consecutive days followed by a week off for up to 11 cycles. Twenty-three lymphoma patients were treated. Ten patients completed the full 11 cycle treatment plan per protocol, 4 patients were removed due to progressive disease, 7 withdrew or were removed from the study due to toxicities. Despite Prevnar vaccine administration every 2 months for 3 injections, the mean antibody concentration never reached protective levels (>0.35 mcg/mL). Fatigue and functional well-being measured by BFI and FACT-G improved significantly from cycle 1 to cycle 7, but the depression scores from the CES-D did not change. Given the toxicities observed, this broad spectrum deacetylase inhibitor at this schedule is not optimal for prolonged maintenance therapy. PMID:25213183

Improving human papilloma virus vaccination rates throughout military treatment facilities.

PubMed

Dawson, Rachel; Lemmon, Keith; Trivedi, Nidhi J; Hansen, Shana

2018-03-07

The four objectives of this study were to (1) educate military healthcare providers on HPV disease and vaccine, (2) assess short term recall of information presented at educational sessions, (3) assess provider comfort level with the vaccine, and (4) assess improvement in HPV vaccination rates. Standardized interactive educational sessions were conducted at military primary care clinics with pre- and post-educational quizzes administered before and immediately following the sessions. Provider attitudes were assessed using Likert scale questionnaires. Vaccination rates in children and young adolescents ages 11-18 at one of the participating regions that had a champion and started a Quality Improvement (QI) project were assessed at baseline, at 3-months and at 6-months post sessions. 200 providers were reached at 48 primary care clinics during May 2014 through October 2015 with 200 quizzes and Likert scale questionnaires returned. There was increase in knowledge following the educational sessions as revealed in the pre- and post- test scores [t(57) = -5.04, p < 0.001]. There was a significant overall increase in comfort in answering patients' and parents' questions about HPV vaccine [p = 0.003]. There was a significant increase in the number of vaccines given at all the clinics 3-months after the educational sessions at the region who had a champion dedicated to monitoring vaccine rates and ensuring implementation efforts [p = 0.01] and started a QI project. This increase was not sustained at 6-months [p = 0.324]. Improvement in provider short term knowledge recall and comfort level in answering parents' questions was seen. We found that educational sessions can improve HPV vaccination rates in military clinics that have a vaccine champion for up to 3-months. Further research into the effects of having clinic vaccine champions is critical. Copyright © 2018. Published by Elsevier Ltd.

Vaccine hesitancy: Causes, consequences, and a call to action.

PubMed

Salmon, Daniel A; Dudley, Matthew Z; Glanz, Jason M; Omer, Saad B

2015-11-27

Vaccine hesitancy reflects concerns about the decision to vaccinate oneself or one's children. There is a broad range of factors contributing to vaccine hesitancy, including the compulsory nature of vaccines, their coincidental temporal relationships to adverse health outcomes, unfamiliarity with vaccine-preventable diseases, and lack of trust in corporations and public health agencies. Although vaccination is a norm in the U.S. and the majority of parents vaccinate their children, many do so amid concerns. The proportion of parents claiming non-medical exemptions to school immunization requirements has been increasing over the past decade. Vaccine refusal has been associated with outbreaks of invasive Haemophilus influenzae type b disease, varicella, pneumococcal disease, measles, and pertussis, resulting in the unnecessary suffering of young children and waste of limited public health resources. Vaccine hesitancy is an extremely important issue that needs to be addressed because effective control of vaccine-preventable diseases generally requires indefinite maintenance of extremely high rates of timely vaccination. The multifactorial and complex causes of vaccine hesitancy require a broad range of approaches on the individual, provider, health system, and national levels. These include standardized measurement tools to quantify and locate clustering of vaccine hesitancy and better understand issues of trust; rapid, independent, and transparent review of an enhanced and appropriately funded vaccine safety system; adequate reimbursement for vaccine risk communication in doctors' offices; and individually tailored messages for parents who have vaccine concerns, especially first-time pregnant women. The potential of vaccines to prevent illness and save lives has never been greater. Yet, that potential is directly dependent on parental acceptance of vaccines, which requires confidence in vaccines, healthcare providers who recommend and administer vaccines, and the

Anti-tau oligomers passive vaccination for the treatment of Alzheimer disease.

PubMed

Kayed, Rakez

2010-11-01

The aggregation and accumulation of the microtubule-associated protein (Tau) is a pathological hallmark of Alzheimer's disease (AD) and many neurodegenerative diseases. Despite the poor correlation between neurofirillary tangles (NFTs) and disease progression, and evidence showing, that neuronal loss in AD actually precedes NFTs formation research until recently focused on them and other large meta-stable inclusions composed of aggregated hyperphosphorylated tau protein. Lately, the significance and toxicity of NFTs has been challenged and new aggregated tau entity has emerged as the true pathogenic species in tauopathies and a possible mediator of Aβ toxicity in AD. Tau intermediate aggregate (tau oligomers; aggregates of an intermediate that is between monomers and NFTs in size) can cause neurodegeneration and memory impairment in the absence of Aβ. This exciting body of evidence includes results from human brain samples, transgenic mouse and cell-based studies. Despite extensive efforts to develop a safe and efficacious vaccine for AD using Aβ peptide as an immunogen in active vaccination approaches or anti Aβ antibodies for passive vaccination, success has been modest. Nonetheless, these studies have produced a wealth of fundamental knowledge that has potential to application to the development of a tau-based immunotherapy. Herein, I discuss the evidence supporting the critical role of tau oligomers in AD, the potential and challenges for targeting them by immunotherapy as a novel approach for AD treatment.

Efficacy of Influenza Vaccination and Tamiflu® Treatment – Comparative Studies with Eurasian Swine Influenza Viruses in Pigs

PubMed Central

Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

2013-01-01

Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs. PMID:23630601

MicroRNA-6826 and -6875 in plasma are valuable non‑invasive biomarkers that predict the efficacy of vaccine treatment against metastatic colorectal cancer.

PubMed

Kijima, Taiki; Hazama, Shoichi; Tsunedomi, Ryouichi; Tanaka, Hironori; Takenouchi, Hiroko; Kanekiyo, Shinsuke; Inoue, Yuka; Nakashima, Masao; Iida, Michihisa; Sakamoto, Kazuhiko; Suzuki, Nobuaki; Takeda, Shigeru; Ueno, Tomio; Yamamoto, Shigeru; Yoshino, Shigefumi; Okuno, Kiyotaka; Nagano, Hiroaki

2017-01-01

Various vaccine treatments against metastatic colorectal cancer have been developed and applied. However, to improve the efficacy of immunotherapy, biomarkers that can predict the effects are needed. It has been reported that various microRNAs (miRNAs) in peripheral blood may be useful as non-invasive biomarkers. In this study, miRNAs influencing the efficacy of vaccine treatment were screened for in a microarray analysis of 13 plasma samples that were obtained from patients prior to vaccine treatment. To validate the screening results, real-time RT-PCR was performed using 93 plasma samples obtained from patients prior to vaccine treatment. Four candidate miRNAs were selected according to the results of the comprehensive analysis of miRNA expression, which were ranked using the Fisher criterion and the absolute value of the log2 ratio in the screening analysis. The validation analysis showed that in the HLA-A*2402‑matched patient group (vaccine-treated group), patients with a high expression of plasma miR-6826 had a poorer prognosis than those with a low expression (P=0.048). In contrast, in the HLA-A*2402-unmatched patient group (control group), there was no difference between the patients with high or low plasma miR-6826 expression (P=0.168). Similar results were obtained in the analysis of miR-6875 (P=0.029 and P=0.754, respectively). Moreover, multivariate analysis of the Cox regression model indicated that the expression of miR-6826 was the most significant predictor for overall survival (P=0.003, hazard ratio, 3.670). In conclusion, plasma miR-6826 and miR-6875 may be predictive biomarkers for a poor response to vaccine treatment. Although further clarification is needed regarding the functions of miR-6826 and miR-6875 and their relationship to immune‑related molecules, plasma miR-6826 and miR-6875 may be useful negative biomarkers for predicting the efficacy of vaccine treatment.

[Yellow fever vaccination in non-immunocompetent patients].

PubMed

Bruyand, M; Receveur, M C; Pistone, T; Verdière, C H; Thiebaut, R; Malvy, D

2008-10-01

Any person travelling in countries where yellow fever (YF) is endemic and without presenting contra-indication for the vaccination against YF may be vaccinated. This vaccination can very rarely induce a potentially lethal neurotropic or viscerotropic disease. In severely immunodeficient patients, the vaccination is contra-indicated because postvaccinal encephalitis may occur after the vaccination, due to vaccine strain pathogenecity. It is important to evaluate the general health status in elderly individuals before vaccinating because of the increased risk of viscerotropic disease in people of 60 years of age and over. Pregnant women should not be vaccinated, except if departure to an endemic zone is unavoidable. YF vaccinatio is contra-indicated for newborns under six months of age. Solid organ grafts, congenital immunodeficiency, leukemia, lymphoma, cancer, and immunosuppressive treatments are contra-indications for this vaccination. Nevertheless, YF immunization is possible after a bone marrow graft and a two-year period without graft-versus-host disease or immunosuppressive treatment. There is no data to support that immunization of the dono prior to the graft could confer protection against yellow fever to the recipient. Low doses, short courses of corticosteroids either as systemic treatment or intra-articular injections are not contra-indications for YF vaccination. Patients infected with HIV with stable clinical status and T CD4-cel count above 200 cells per millimetre cube may be vaccinated. Thymic diseases, including thymoma and thymectomy, are contra-indications for YF vaccination. Finally, a substantial residual level of antibodies beyond 10 years after the latest vaccination could confer protection, thus avoiding a new vaccination when it is an issue.

Current Ebola vaccines

PubMed Central

Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz

2012-01-01

Introduction Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates, with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in non-human primates, the gold standard animal model for Ebola hemorrhagic fever. Areas covered This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios, and describes current ebolavirus vaccines. Among these vaccines are recombinant Adenoviruses, recombinant Vesicular Stomatitis viruses, recombinant Human Parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant Vesicular Stomatitis viruses, has also demonstrated post-exposure protection in non-human primates. Expert opinion The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and towards licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible. PMID:22559078

Engineering new mycobacterial vaccine design for HIV–TB pediatric vaccine vectored by lysine auxotroph of BCG

PubMed Central

Saubi, Narcís; Gea-Mallorquí, Ester; Ferrer, Pau; Hurtado, Carmen; Sánchez-Úbeda, Sara; Eto, Yoshiki; Gatell, Josep M; Hanke, Tomáš; Joseph, Joan

2014-01-01

In this study, we have engineered a new mycobacterial vaccine design by using an antibiotic-free plasmid selection system. We assembled a novel Escherichia coli (E. coli)–mycobacterial shuttle plasmid p2auxo.HIVA, expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance based on glycine complementation in E. coli and lysine complementation in mycobacteria. This plasmid was first transformed into glycine auxotroph of E. coli strain and subsequently transformed into lysine auxotroph of Mycobacterium bovis BCG strain to generate vaccine BCG.HIVA2auxo. We demonstrated that the episomal plasmid p2auxo.HIVA was stable in vivo over a 7-week period and genetically and phenotypically characterized the BCG.HIVA2auxo vaccine strain. The BCG.HIVA2auxo vaccine in combination with modified vaccinia virus Ankara (MVA). HIVA was safe and induced HIV-1 and Mycobacterium tuberculosis-specific interferon-γ-producing T-cell responses in adult BALB/c mice. Polyfunctional HIV-1-specific CD8+ T cells, which produce interferon-γ and tumor necrosis factor-α and express the degranulation marker CD107a, were induced. Thus, we engineered a novel, safer, good laboratory practice–compatible BCG-vectored vaccine using prototype immunogen HIVA. This antibiotic-free plasmid selection system based on “double” auxotrophic complementation might be a new mycobacterial vaccine platform to develop not only recombinant BCG-based vaccines expressing second generation of HIV-1 immunogens but also other major pediatric pathogens to prime protective response soon after birth. PMID:26015961

Transmission Dynamics of Rift Valley Fever Virus: Effects of Live and Killed Vaccines on Epizootic Outbreaks and Enzootic Maintenance

PubMed Central

Chamchod, Farida; Cosner, Chris; Cantrell, R. Stephen; Beier, John C.; Ruan, Shigui

2016-01-01

Rift Valley fever virus (RVFV) is an arthropod-borne viral pathogen that causes significant morbidity and mortality in small ruminants throughout Africa and the Middle East. Due to the sporadic and explosive nature of RVF outbreaks, vaccination has proved challenging to reduce RVFV infection in the ruminant population. Currently, there are two available types of vaccines, live and killed, in endemic areas. In this study, two mathematical models have been developed to explore the impact of live and killed vaccines on the transmission dynamics of RVFV. We demonstrate in general that vaccination helps reduce the severity of RVF outbreaks and that less delay in implementation and more vaccination attempts and effective vaccines can reduce the outbreak magnitude and the endemic number of RVFV. However, an introduction of a number of ruminants vaccinated by live vaccines in RVFV-free areas may cause an outbreak and RVFV may become endemic if there is sustained use of live vaccines. Other factors that are the important determinants of RVF outbreaks include: unsustained vaccination programs, recruitment of susceptible ruminants, and the seasonal abundance of mosquitoes. PMID:26869999

The Effect of a Multiple Treatment Program and Maintenance Procedures on Smoking Cessation.

ERIC Educational Resources Information Center

Powell, Don R.

The efficacy of a multiple treatment smoking cessation program and three maintenance strategies was evaluated. Phases I and II of the study involved 51 subjects who participated in a five-day smoking cessation project consisting of lectures, demonstrations, practice exercises, negative smoking, and the teaching of self-control procedures. At the…

Impact of Cannabis Use During Stabilization on Methadone Maintenance Treatment

PubMed Central

Scavone, Jillian L.; Sterling, Robert C.; Weinstein, Stephen P.; Van Bockstaele, Elisabeth J.

2016-01-01

Background and Objectives Illicit drug use, particularly of cannabis, is common among opiate-dependent individuals, and has the potential to impact treatment in a negative manner. Methods To examine this, patterns of cannabis use prior to and during methadone maintenance treatment (MMT) were examined to assess possible cannabis-related effects on MMT, particularly during methadone stabilization. Retrospective chart analysis was used to examine outpatient records of patients undergoing MMT (n=91), focusing specifically on past and present cannabis use and its association with opiate abstinence, methadone dose stabilization, and treatment compliance. Results Objective rates of cannabis use were high during methadone induction, dropping significantly following dose stabilization. History of cannabis use correlated with cannabis use during MMT, but did not negatively impact the methadone induction process. Pilot data also suggested that objective ratings of opiate withdrawal decrease in MMT patients using cannabis during stabilization. Conclusions and Scientific Significance The present findings may point to novel interventions to be employed during treatment for opiate dependence that specifically target cannabinoid-opioid system interactions. PMID:23795873

Maintenance of head and neck tumor on-chip: gateway to personalized treatment?

PubMed Central

Bower, Ruth; Green, Victoria L; Kuvshinova, Elena; Kuvshinov, Dmitriy; Karsai, Laszlo; Crank, Stephen T; Stafford, Nicholas D; Greenman, John

2017-01-01

Aim: Head and neck squamous cell carcinomas (HNSCC) are solid tumors with low overall survival (40–60%). In a move toward personalized medicine, maintenance of tumor biopsies in microfluidic tissue culture devices is being developed. Methodology/results: HNSCC (n = 15) was dissected (5–10 mg) and either analyzed immediately or cultured in a microfluidic device (37°C) for 48 h. No difference was observed in morphology between pre- and postculture specimens. Dissociated samples were analyzed using trypan blue exclusion (viability), propidium iodide flow cytometry (death) and MTS assay (proliferation) with no significant difference observed highlighting tissue maintenance. Computational fluid dynamics showed laminar flow within the system. Conclusion: The microfluidic culture system successfully maintained HNSCC for 48 h, the culture system will allow testing of different treatment modalities with response monitoring. PMID:28670466

T-cell-mediated immune response to pneumococcal conjugate vaccine (PCV-13) and tetanus toxoid vaccine in patients with moderate-to-severe psoriasis during tofacitinib treatment.

PubMed

Winthrop, Kevin L; Korman, Neil; Abramovits, William; Rottinghaus, Scott T; Tan, Huaming; Gardner, Annie; Mukwaya, Geoffrey; Kaur, Mandeep; Valdez, Hernan

2018-06-01

Psoriasis is often treated with immunomodulatory therapies that can affect the immune response to common antigens. Tofacitinib is an oral Janus kinase inhibitor. To characterize the effect of long-term exposure to tofacitinib 10 mg twice daily on T-cell function in psoriasis patients. Patients completing at least 3 months' continuous treatment with tofacitinib 10 mg twice daily were vaccinated with T-cell-dependent vaccines (monovalent tetanus toxoid and 13-valent pneumococcal conjugate [PCV-13]). Patients were assessed at baseline (before vaccination) and then again 4 weeks after vaccination. For PCV-13, we evaluated serotype-specific, opsonophagocytic antibody responses, and for tetanus toxoid, we evaluated humoral responses. Among 60 patients who completed the study, the geometric mean fold rise from baseline for the 13 PCV serotypes at 4 weeks postvaccination varied from 8.3 (serotype 3) to 101.9 (serotype 6A). Similar results were observed for patients with and without lymphopenia at baseline. For tetanus toxoid, 51 (88%) patients had ≥2-fold and 35 (60%) patients had ≥4-fold rise in antibody concentration. There was no placebo control. Most psoriasis patients who receive tofacitinib can mount satisfactory T-cell-dependent responses to PCV-13 and tetanus vaccines. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Vaccine Immunotherapy for Prostate Cancer

DTIC Science & Technology

2012-05-01

adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols have been used in the trial: #1 - Phase II study of Adenovirus/PSA...this award is to conduct a Phase II clinical trial (Study) of an adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols...suddenly prior to study treatment . And one patient previously reported as a screen failure became eligible and was treated. This subject was not

Traditional Chinese Medicine treatment as maintenance therapy in advanced non-small-cell lung cancer: A randomized controlled trial.

PubMed

Jiang, Yi; Liu, Ling-Shuang; Shen, Li-Ping; Han, Zhi-Fen; Jian, Hong; Liu, Jia-Xiang; Xu, Ling; Li, He-Gen; Tian, Jian-Hui; Mao, Zhu-Jun

2016-02-01

Maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) is an increasingly hot topic in the field of clinical NSCLC research. This study aimed to evaluate the effects of Traditional Chinese Medicine (TCM) treatment as maintenance therapy on time to progression (TTP), quality of life (QOL), overall survival (OS) and 1-year survival rate in patients with advanced NSCLC. This study was conducted as a randomized, controlled, open-label trial. 64 non-progressive patients who responded to initial therapy were randomized 1:1 to the TCM arm (treated with herbal injection (Cinobufacini, 20ml/d, d1-d10), herbal decoction (d1-d21) and Chinese acupoint application (d1-d21), n=32) or to the chemotherapy arm (treated with pemetrexed (non-squamous NSCLC, 500mg/m(2), d1), docetaxel (75mg/m(2), d1) or gemcitabine (1250mg/m(2), d1 and d8), n=32). Each therapy cycle was 21 days. They were repeated until disease progression, unacceptable toxicity, or until the patients requested therapy discontinuation. The primary end point was TTP; the secondary end points were QOL, OS and 1-year survival rate. "Intention-to-treat" analysis included all randomized participants. TCM treatment prolonged median TTP for 0.7 months compared with chemotherapy, but it was not statistically significant (3.0 months vs. 2.3 months, P=0.114). Median OS time for TCM treatment did not offer a significant advantage over for chemotherapy (21.5 months vs. 18.8 months, P=0.601). 1-year survival rate of TCM treatment significantly improved than that of chemotherapy (78.1% vs. 53.1%, P=0.035). TCM treatment can significantly improve QOL when compared to chemotherapy as assessed by EORTC QLQ-C30 and EORTC QLQ-LC13 QOL instruments. TCM maintenance treatment had similar effects on TTP and OS compared with maintenance chemotherapy, but it improved patients' QOL and had higher 1-year survival rate. TCM Maintenance treatment is a promising option for advanced NSCLC patients without progression

Maintenance Solutions for Bleeding and Flushed Pavements Surfaced with a Seal Coat or Surface Treatment

DOT National Transportation Integrated Search

2007-02-01

This report summarizes the findings of research directed at identifying maintenance solutions for bleeding and : flushed asphalt pavements surfaced with seal coats or surface treatments. Although the basic mechanism associated with : both bleeding an...

Therapeutic cancer vaccines

PubMed Central

Melief, Cornelis J.M.; van Hall, Thorbald; Arens, Ramon; Ossendorp, Ferry; van der Burg, Sjoerd H.

2015-01-01

The clinical benefit of therapeutic cancer vaccines has been established. Whereas regression of lesions was shown for premalignant lesions caused by HPV, clinical benefit in cancer patients was mostly noted as prolonged survival. Suboptimal vaccine design and an immunosuppressive cancer microenvironment are the root causes of the lack of cancer eradication. Effective cancer vaccines deliver concentrated antigen to both HLA class I and II molecules of DCs, promoting both CD4 and CD8 T cell responses. Optimal vaccine platforms include DNA and RNA vaccines and synthetic long peptides. Antigens of choice include mutant sequences, selected cancer testis antigens, and viral antigens. Drugs or physical treatments can mitigate the immunosuppressive cancer microenvironment and include chemotherapeutics, radiation, indoleamine 2,3-dioxygenase (IDO) inhibitors, inhibitors of T cell checkpoints, agonists of selected TNF receptor family members, and inhibitors of undesirable cytokines. The specificity of therapeutic vaccination combined with such immunomodulation offers an attractive avenue for the development of future cancer therapies. PMID:26214521

Vaccines for Canine Leishmaniasis

PubMed Central

Palatnik-de-Sousa, Clarisa B.

2012-01-01

Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL. PMID:22566950

Association between the DRD2 A1 allele and response to methadone and buprenorphine maintenance treatments.

PubMed

Barratt, Daniel T; Coller, Janet K; Somogyi, Andrew A

2006-06-05

The TaqI A polymorphism (A(1)) of the dopamine D(2) receptor gene (DRD2), although not a specific predictor of opioid dependence, has been strongly associated with high levels of prior heroin use and poor treatment outcomes among methadone maintenance patients. The aims of this study were to confirm these findings via a retrospective analysis of A(1) allele frequency in methadone (n = 46) and buprenorphine (n = 25) patients, and non-opioid-dependent controls (n = 95). Subjects were genotyped at the DRD2 TaqI A locus using PCR amplification followed by TaqI restriction enzyme digestion and gel electrophoresis. For methadone and buprenorphine subjects, heroin use (prior to treatment), treatment outcomes, and withdrawal occurrence were determined from comprehensive case notes. No significant differences in A(1) allele frequency (%) were observed between: methadone (19.6%), buprenorphine (18.0%), and control (17.9%) groups (P > 0.7); successful and poor treatment outcome groups, methadone: 20.0% and 19.2%, respectively (P = 1.0); buprenorphine: 18.4% and 20.0%, respectively (P = 1.0). Also, there were no significant relationships between TaqI A genotype and prior heroin use (P = 0.47). However, among the successful methadone subjects, significantly fewer A(1) allele carriers experienced withdrawal than non-A(1) carriers (P = 0.04). In conclusion, the DRD2 genotype effects did not affect opioid maintenance treatment outcomes. This suggests the need for a further prospective investigation into the role of the DRD2 A(1) allele in heroin use and response to maintenance pharmacotherapies for opioid dependence.

A randomized controlled trial of interim methadone maintenance.

PubMed

Schwartz, Robert P; Highfield, David A; Jaffe, Jerome H; Brady, Joseph V; Butler, Carol B; Rouse, Charles O; Callaman, Jason M; O'Grady, Kevin E; Battjes, Robert J

2006-01-01

Effective alternatives to long waiting lists for entry into methadone hydrochloride maintenance treatment are needed to reduce the complications of continuing heroin dependence and to increase methadone treatment entry. To compare the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry and reducing heroin and cocaine use and criminal behavior. Randomized, controlled, clinical trial using 2 conditions, with treatment assignment on a 3:2 basis to interim maintenance-waiting list control. A methadone treatment program in Baltimore. A total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment. Participants were randomly assigned to either interim methadone maintenance, consisting of an individually determined methadone dose and emergency counseling only for up to 120 days, or referral to community-based methadone treatment programs. Entry into comprehensive methadone maintenance therapy at 4 months from baseline; self-reported days of heroin use, cocaine use, and criminal behavior; and number of urine drug test results positive for heroin and cocaine at the follow-up interview conducted at time of entry into comprehensive methadone treatment (or at 4 months from baseline for participants who did not enter regular treatment). Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline (75.9%) than those assigned to the waiting list control condition (20.8%) (P<.001). Overall, in the past 30 days at follow-up, interim participants reported significantly fewer days of heroin use (P<.001), had a significant reduction in heroin-positive drug test results (P<.001), reported spending less money on drugs (P<.001), and received less illegal income (P<.02) than the waiting list participants. Interim methadone maintenance results in a

Generalization and Maintenance of Treatment Gains in Primary Progressive Aphasia (PPA): A Systematic Review

ERIC Educational Resources Information Center

Cadório, Inês; Lousada, Marisa; Martins, Paula; Figueiredo, Daniela

2017-01-01

Background: Cognitive-linguistic treatments and interventions targeting communication have been developed within the context of primary progressive aphasia (PPA), however knowledge about the scope of generalization and maintenance of therapy gains considering PPA subtypes remains scarce and awaits systematic investigation. Aims: To analyse the…

Use of contingency management incentives to improve completion of hepatitis B vaccination in people undergoing treatment for heroin dependence: a cluster randomised trial.

PubMed

Weaver, Tim; Metrebian, Nicola; Hellier, Jennifer; Pilling, Stephen; Charles, Vikki; Little, Nicholas; Poovendran, Dilkushi; Mitcheson, Luke; Ryan, Frank; Bowden-Jones, Owen; Dunn, John; Glasper, Anthony; Finch, Emily; Strang, John

2014-07-12

Poor adherence to treatment diminishes its individual and public health benefit. Financial incentives, provided on the condition of treatment attendance, could address this problem. Injecting drug users are a high-risk group for hepatitis B virus (HBV) infection and transmission, but adherence to vaccination programmes is poor. We aimed to assess whether contingency management delivered in routine clinical practice increased the completion of HBV vaccination in individuals receiving opioid substitution therapy. In our cluster randomised controlled trial, we enrolled participants at 12 National Health Service drug treatment services in the UK that provided opioid substitution therapy and nurse-led HBV vaccination with a super-accelerated schedule (vaccination days 0, 7, and 21). Clusters were randomly allocated 1:1:1 to provide vaccination without incentive (treatment as usual), with fixed value contingency management (three £10 vouchers), or escalating value contingency management (£5, £10, and £15 vouchers). Both contingency management schedules rewarded on-time attendance at appointments. The primary outcome was completion of clinically appropriate HBV vaccination within 28 days. We also did sensitivity analyses that examined vaccination completion with full adherence to appointment times and within a 3 month window. The trial is registered with Current Controlled Trials, number ISRCTN72794493. Between March 16, 2011, and April 26, 2012, we enrolled 210 eligible participants. Compared with six (9%) of 67 participants treated as usual, 35 (45%) of 78 participants in the fixed value contingency management group met the primary outcome measure (odds ratio 12·1, 95% CI 3·7-39·9; p<0·0001), as did 32 (49%) of 65 participants in the escalating value contingency management group (14·0, 4·2-46·2; p<0·0001). These differences remained significant with sensitivity analyses. Modest financial incentives delivered in routine clinical practice significantly improve

Severe anorexia nervosa, co-occurring major depressive disorder and electroconvulsive therapy as maintenance treatment: a case report.

PubMed

Poutanen, Outi; Huuhka, Kaija; Perko, Kaisa

2009-12-21

It is difficult to treat patients who, in addition to having severe anorexia nervosa, also have severe symptoms of major depressive disorder and a tendency for impulsive acting out behaviour. Our case report considers the feasibility of maintenance electroconvulsive therapy in such complicated cases. This is a case report of a woman with anorexia nervosa and co-morbid severe major depressive disorder who was treated with electroconvulsive therapy as a maintenance treatment. The maintenance electroconvulsive therapy was conducted without immediate complications. It had a positive effect on the patient's depressive symptoms and lability and her general wellbeing, although some cognitive deficits were observed. The maintenance electroconvulsive therapy seemed to support recovery in a case of refractory anorexia nervosa and a tendency for labile mood. The symptoms of co-occurring major depressive disorder were partly relieved and maintenance electroconvulsive therapy had some positive effect on weight gain.

Medicaid patients in a private health maintenance organization: patterns of chemical dependency treatment.

PubMed

Walter, Lawrence J; Parthasarathy, Sujaya; Allen, Steven; Ackerson, Lynn

2002-02-01

Although many Medicaid beneficiaries receive health care through commercial health maintenance organizations (HMOs), the impact of private managed care on low-income individuals seeking treatment for substance abuse has rarely been studied. This study examined treatment patterns of 234 Medicaid recipients who presented for care at an HMO between 1995 and 1997. After adjustment for demographic factors and duration of health plan membership, the Medicaid patients returned to start treatment after intake less often (odds ratio = 0.60) and dropped out of treatment sooner (median = 14 versus 28 days) than non-Medicaid patients. While many Medicaid patients received significant amounts of substance abuse treatment, further research is needed to explain the observed treatment gap and to identify areas where HMOs can improve services for some of their most vulnerable members.

ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics

PubMed Central

Barratt, Daniel T; Coller, Janet K; Hallinan, Richard; Byrne, Andrew; White, Jason M; Foster, David JR; Somogyi, Andrew A

2012-01-01

Background: Genetic variability in ABCB1, encoding the P-glycoprotein efflux transporter, has been linked to altered methadone maintenance treatment dose requirements. However, subsequent studies have indicated that additional environmental or genetic factors may confound ABCB1 pharmacogenetics in different methadone maintenance treatment settings. There is evidence that genetic variability in OPRM1, encoding the mu opioid receptor, and ABCB1 may interact to affect morphine response in opposite ways. This study aimed to examine whether a similar gene-gene interaction occurs for methadone in methadone maintenance treatment. Methods: Opioid-dependent subjects (n = 119) maintained on methadone (15–300 mg/day) were genotyped for five single nucleotide polymorphisms of ABCB1 (61A > G; 1199G > A; 1236C > T; 2677G > T; 3435C > T), as well as for the OPRM1 118A > G single nucleotide polymorphism. Subjects’ methadone doses and trough plasma (R)-methadone concentrations (Ctrough) were compared between ABCB1 haplotypes (with and without controlling for OPRM1 genotype), and between OPRM1 genotypes (with and without controlling for ABCB1 haplotype). Results: Among wild-type OPRM1 subjects, an ABCB1 variant haplotype group (subjects with a wild-type and 61A:1199G:1236C:2677T:3435T haplotype combination, or homozygous for the 61A:1199G:1236C:2677T:3435T haplotype) had significantly lower doses (median ± standard deviation 35 ± 5 versus 180 ± 65 mg/day, P < 0.01) and Ctrough (78 ± 22 versus 177 ± 97 ng/mL, P < 0.05) than ABCB1 wild-type subjects. Among subjects with the most common ABCB1 haplotype combination (wild-type with 61A:1199G:1236T:2677T:3435T), the OPRM1 118 A/G genotype was associated with a significantly higher Ctrough than 118 A/A (250 ± 126 versus 108 ± 36 ng/mL, P = 0.016). No ABCB1 haplotype group or OPRM1 genotype was associated with dose or Ctrough without taking into account confounding genetic variability at the other locus. Therefore, two

Lifestyle Vaccines and Public Health: Exploring Policy Options for a Vaccine to Stop Smoking.

PubMed

Wolters, Anna; de Wert, Guido; van Schayck, Onno C P; Horstman, Klasien

2016-07-01

Experimental vaccines are being developed for the treatment of 'unhealthy lifestyles' and associated chronic illnesses. Policymakers and other stakeholders will have to deal with the ethical issues that this innovation path raises: are there morally justified reasons to integrate these innovative biotechnologies in future health policies? Should public money be invested in further research? Focusing on the case of an experimental nicotine vaccine, this article explores the ethical aspects of 'lifestyle vaccines' for public health. Based on findings from a qualitative study into a vaccine for smoking cessation, the article articulates possible value conflicts related to nicotine vaccination as an intervention in tobacco control. The 'vaccinization' of lifestyle disease piggybacks on the achievements of classic vaccines. Contrary to expectations of simplicity and success, quitting smoking with a vaccine requires a complex supportive network. Social justice and public trust may become important ethical challenges when deciding whether to use further public funds for research or whether to implement these innovative vaccines in the future.

Vaccine instability in the cold chain: mechanisms, analysis and formulation strategies.

PubMed

Kumru, Ozan S; Joshi, Sangeeta B; Smith, Dawn E; Middaugh, C Russell; Prusik, Ted; Volkin, David B

2014-09-01

Instability of vaccines often emerges as a key challenge during clinical development (lab to clinic) as well as commercial distribution (factory to patient). To yield stable, efficacious vaccine dosage forms for human use, successful formulation strategies must address a combination of interrelated topics including stabilization of antigens, selection of appropriate adjuvants, and development of stability-indicating analytical methods. This review covers key concepts in understanding the causes and mechanisms of vaccine instability including (1) the complex and delicate nature of antigen structures (e.g., viruses, proteins, carbohydrates, protein-carbohydrate conjugates, etc.), (2) use of adjuvants to further enhance immune responses, (3) development of physicochemical and biological assays to assess vaccine integrity and potency, and (4) stabilization strategies to protect vaccine antigens and adjuvants (and their interactions) during storage. Despite these challenges, vaccines can usually be sufficiently stabilized for use as medicines through a combination of formulation approaches combined with maintenance of an efficient cold chain (manufacturing, distribution, storage and administration). Several illustrative case studies are described regarding mechanisms of vaccine instability along with formulation approaches for stabilization within the vaccine cold chain. These include live, attenuated (measles, polio) and inactivated (influenza, polio) viral vaccines as well as recombinant protein (hepatitis B) vaccines. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Nicotine vaccines to treat tobacco dependence

PubMed Central

Goniewicz, Maciej L.; Delijewski, Marcin

2013-01-01

Tobacco smoking is globally far more widespread than use of any other substance of abuse. Nicotine is an important tobacco constituent that is responsible for addictive properties of smoking. The currently available medications for the treatment of nicotine addiction have limited efficacy. A challenging novel therapeutic concept is vaccination against nicotine. An efficient vaccine would generate antibodies that sequester nicotine in the blood and prevent its access to the brain. The vaccine would have great potential for treating nicotine addiction and for relapse prevention. We reviewed the current status of vaccines against nicotine addiction that are undergoing clinical trials or are in preclinical development. We discuss problems associated with the development of nicotine vaccines, their efficacy in addiction treatment, challenges and ethical concerns. Existing evidence indicates that nicotine vaccination is well tolerated and capable of inducing an immune response but its effectiveness in increasing smoking abstinence has not been shown so far. PMID:23108361

Prevention and synergistic control of Ph(+) ALL by a DNA vaccine and 6-mercaptopurine.

PubMed

Köchling, Joachim; Rott, Yvonne; Arndt, Stefanie; Marschke, Christina; Schmidt, Manuel; Wittig, Burghardt; Kalies, Katrin; Westermann, Jürgen; Henze, Günter

2012-09-07

Although the outcome of patients with acute lymphoblastic leukemia (ALL) has been improved continuously by chemotherapy and tyrosine kinase inhibitors, prognosis of patients with Philadelphia chromosome positive (Ph(+)) ALL still remains poor. Since further intensification of chemotherapy is limited by toxic side effects and patients with high risk of transplant-related mortality are not eligible for allogeneic stem cell transplantation new treatment strategies are urgently needed for the prevention of Ph(+) ALL relapse. There is increasing evidence that the immune system plays an essential role for the eradication or immunologic control of remaining leukemia cells. We developed several DNA-based vaccines encoding a BCR-ABL(p185) specific peptide and GM-CSF, and CD40-L, IL-27 or IL-12 and evaluated the preventive and therapeutic efficacy against a lethal challenge of syngeneic Ph(+) ALL in Balb/c mice. In vivo cell depletion assays and cytokine expression studies were performed and the efficacy of the DNA vaccine was compared with 6-mercaptopurine (6-MP) alone and the combination of the DNA vaccine and 6-MP. Preventive immunization with the vaccine BCR-ABL/GM-CSF/IL-12 and the TLR-9 agonist dSLIM induced an innate and adaptive immune response mediated by NK-cells, CD4(+) T-cells and CD8(+) T-cells leading to a survival rate of 80%. Therapeutic vaccination resulted in a significantly longer leukemia-free survival (40.7 days vs. 20.4 days) and a higher survival rate (56% vs. 10%) compared to chemotherapy with 6-MP. Remarkably, in combination with the vaccine 6-MP acted synergistically and led to 100% survival. These results demonstrate that minimal residual disease of Ph(+) ALL can be significantly better controlled by a combined treatment approach of immunotherapy and chemotherapy. This provides a rationale for improving maintenance therapy in order to reduce the relapse rate in patients with Ph(+) ALL. Copyright © 2012 Elsevier Ltd. All rights reserved.

Implementing methadone maintenance treatment in prisons in Malaysia.

PubMed

Wickersham, Jeffrey A; Marcus, Ruthanne; Kamarulzaman, Adeeba; Zahari, Muhammad Muhsin; Altice, Frederick L

2013-02-01

In Malaysia, human immunodeficiency virus (HIV) infection is highly concentrated among people who inject opioids. For this reason, the country undertook a three-phase roll-out of a methadone maintenance treatment (MMT) programme. In Phase 3, described in this paper, MMT was implemented within prisons and retention in care was assessed. After developing standard operating procedures and agreement between its Prisons Department and Ministry of Health, Malaysia established pilot MMT programmes in two prisons in the states of Kelantan (2008) and Selangor (2009) - those with the highest proportions of HIV-infected prisoners. Community-based MMT programmes were also established in Malaysia to integrate treatment activities after prisoners' release. Having failed to reduce the incidence of HIV infection, in 2005 Malaysia embarked on a harm reduction strategy. STANDARD OPERATING PROCEDURES WERE MODIFIED TO: (i) escalate the dose of methadone more slowly; (ii) provide ongoing education and training for medical and correctional staff and inmates; (iii) increase the duration of methadone treatment before releasing prisoners; (iv) reinforce linkages with community MMT programmes after prisoners' release; (v) screen for and treat tuberculosis; (vi) escalate the dose of methadone during treatment for HIV infection and tuberculosis; and (vii) optimize the daily oral dose of methadone (> 80 mg) before releasing prisoners. Prison-based MMT programmes can be effectively implemented but require adequate dosing and measures are needed to improve communication between prison and police authorities, prevent police harassment of MMT clients after their release, and improve systems for tracking release dates.

Maintenance treatment of duodenal ulceration: ranitidine 300 mg at night is better than 150 mg in cigarette smokers.

PubMed Central

Lee, F I; Hardman, M; Jaderberg, M E

1991-01-01

Two hundred patients received either ranitidine 150 mg or 300 mg at night for 18 months to prevent duodenal ulcer relapse. Recurrence rates were lower in patients receiving the higher dose of ranitidine (3.1% v 9.7%, p = 0.78; 6.5% v 16.7%, p = 0.037; and 8.9% v 17.0%, p = 0.121 at six, 12, and 18 months respectively). In patients receiving ranitidine 150 mg, recurrences were significantly more common in smokers than non-smokers after 12 and 18 months, while in patients receiving ranitidine 300 mg recurrence rates were similar in smokers and non-smokers. Ranitidine 300 mg at night abolishes the adverse effect of smoking observed during maintenance treatment with ranitidine 150 mg at night and may therefore be an appropriate maintenance dose for smokers who relapse during standard dose maintenance treatment. PMID:1864532

Aripiprazole in the Maintenance Treatment of Bipolar Disorder: A Critical Review of the Evidence and Its Dissemination into the Scientific Literature

PubMed Central

Jureidini, Jon N.; Parry, Peter I.; Spielmans, Glen I.; Healy, David

2011-01-01

Background Aripiprazole, a second-generation antipsychotic medication, has been increasingly used in the maintenance treatment of bipolar disorder and received approval from the U.S. Food and Drug Administration for this indication in 2005. Given its widespread use, we sought to critically review the evidence supporting the use of aripiprazole in the maintenance treatment of bipolar disorder and examine how that evidence has been disseminated in the scientific literature. Methods and Findings We systematically searched multiple databases to identify double-blind, randomized controlled trials of aripiprazole for the maintenance treatment of bipolar disorder while excluding other types of studies, such as open-label, acute, and adjunctive studies. We then used a citation search to identify articles that cited these trials and rated the quality of their citations. Our evidence search protocol identified only two publications, both describing the results of a single trial conducted by Keck et al., which met criteria for inclusion in this review. We describe four issues that limit the interpretation of that trial as supporting the use of aripiprazole for bipolar maintenance: (1) insufficient duration to demonstrate maintenance efficacy; (2) limited generalizability due to its enriched sample; (3) possible conflation of iatrogenic adverse effects of abrupt medication discontinuation with beneficial effects of treatment; and (4) a low overall completion rate. Our citation search protocol yielded 80 publications that cited the Keck et al. trial in discussing the use of aripiprazole for bipolar maintenance. Of these, only 24 (30%) mentioned adverse events reported and four (5%) mentioned study limitations. Conclusions A single trial by Keck et al. represents the entirety of the literature on the use of aripiprazole for the maintenance treatment of bipolar disorder. Although careful review identifies four critical limitations to the trial's interpretation and overall utility

Vaccination and allergy.

PubMed

Rottem, Menachem; Shoenfeld, Yehuda

2004-06-01

Vaccines have had a major effect on controlling the spread of infectious diseases, but use of certain vaccines was linked to potential allergic and autoimmune side effects in healthy and often in certain high-risk populations. In this review the authors summarize the current knowledge of such risks. Immediate systemic allergic reactions after vaccination with commonly used vaccines are extremely rare. Use of certain vaccines was linked to potential allergic side effects in healthy and often in certain high-risk populations. The authors review the data on the risk associated with important vaccines including influenza, smallpox, pneumococcus, Japanese encephalitis, Bacille Calmette-Guerin, pertussis, and measles, mumps, and rubella. Two main components were identified as a source for allergic reactions in vaccines: gelatin and egg protein. There is growing interest in the potential interactions between infant vaccination and risk for development of atopic disease. In addition, there is concern that genetic risk for atopy influences capacity to respond to vaccination during infancy. There is no evidence that vaccines such as Bacille Calmette-Guerin; pertussis; influenza; measles, mumps, and rubella; or smallpox have an effect on the risk of the development of atopy later in life. Immunotherapy provides an efficacious and safe method for the treatment of allergic conditions by immunomodulation of the immune system. The possibility of vaccination triggering or unmasking autoimmunity in genetically susceptible individuals cannot be ruled out, but for the general population the risk-to-benefit ratio is overwhelmingly in favor of vaccinations. Childhood vaccination remains an essential part of child health programs and should not be withheld, even from children predisposed to allergy. Vaccinations are safe, but special attention should be taken in high-risk individuals with anaphylactic reactions to foods, and in patients with autoimmune diseases.

The relationship between vulnerable attachment style, psychopathology, drug abuse, and retention in treatment among methadone maintenance treatment patients.

PubMed

Potik, David; Peles, Einat; Abramsohn, Yahli; Adelson, Miriam; Schreiber, Shaul

2014-01-01

The relationship between vulnerable attachment style, psychopathology, drug abuse, and retention in treatment among patients in methadone maintenance treatment (MMT) was examined by the Vulnerable Attachment Style Questionnaire (VASQ), the Symptom Checklist-90 (SCL-90), and drug abuse urine tests. After six years, retention in treatment and repeated urine test results were studied. Patients with vulnerable attachment style (a high VASQ score) had higher rates of drug abuse and higher psychopathology levels compared to patients with secure attachment style, especially on the interpersonal sensitivity, anxiety, hostility, phobic anxiety, and paranoid ideation scales. Drug abstinence at baseline was related to retention in treatment and to higher rates of drug abstinence after six years in MMT, whereas a vulnerable attachment style could not predict drug abstinence and retention in treatment. Clinical Implications concerning treatment of drug abusing populations and methodological issues concerning the VASQ's subscales are also discussed.

The effect of stimulant and sedative use on treatment outcome of patients admitted to methadone maintenance treatment.

PubMed

DeMaria, P A; Sterling, R; Weinstein, S P

2000-01-01

While methadone maintenance treatment (MMT) has been demonstrated to be an effective treatment for opiate dependence, its impact on the treatment outcome of other illicit drug abuse is not as clear. Using the initial urine drug screen (UDS) and follow-up UDS at 1, 6, 12, and 24 months, 167 patients consecutively admitted to MMT were evaluated for opiate, sedative (predominantly benzodiazepine), and stimulant (predominantly cocaine) use. Retention for the opiate only group was 97.32 days longer on average than for patients using opiates along with stimulants, sedatives, or both stimulants and sedatives. Patients abusing opiates only had the greatest decrease in drug use; however, MMT was also associated with decreases in cocaine and sedative use over the 24 month follow-up period. There was no evidence that patients "switched" their drugs of abuse with time in treatment. The negative impact of non-opiate drug use on outcome in MMT and its implications for treatment planning are discussed.

A treatment for and vaccine against the deadly Hendra and Nipah viruses.

PubMed

Broder, Christopher C; Xu, Kai; Nikolov, Dimitar B; Zhu, Zhongyu; Dimitrov, Dimiter S; Middleton, Deborah; Pallister, Jackie; Geisbert, Thomas W; Bossart, Katharine N; Wang, Lin-Fa

2013-10-01

Hendra virus and Nipah virus are bat-borne paramyxoviruses that are the prototypic members of the genus Henipavirus. The henipaviruses emerged in the 1990s, spilling over from their natural bat hosts and causing serious disease outbreaks in humans and livestock. Hendra virus emerged in Australia and since 1994 there have been 7 human infections with 4 case fatalities. Nipah virus first appeared in Malaysia and subsequent outbreaks have occurred in Bangladesh and India. In total, there have been an estimated 582 human cases of Nipah virus and of these, 54% were fatal. Their broad species tropism and ability to cause fatal respiratory and/or neurologic disease in humans and animals make them important transboundary biological threats. Recent experimental findings in animals have demonstrated that a human monoclonal antibody targeting the viral G glycoprotein is an effective post-exposure treatment against Hendra and Nipah virus infection. In addition, a subunit vaccine based on the G glycoprotein of Hendra virus affords protection against Hendra and Nipah virus challenge. The vaccine has been developed for use in horses in Australia and is the first vaccine against a Biosafety Level-4 (BSL-4) agent to be licensed and commercially deployed. Together, these advances offer viable approaches to address Hendra and Nipah virus infection of livestock and people. Published by Elsevier B.V.

Macromolecular systems for vaccine delivery.

PubMed

MuŽíková, G; Laga, R

2016-10-20

Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature.

[Cost-effectiveness of Antipsychotics in the Maintenance Treatment of Schizophrenia in Colombia].

PubMed

Quitian Reyes, Hoover; Arciniegas Barrera, Jair Alberto; Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos

2016-01-01

Assess the cost-effectiveness of the antipsychotics for treatment of schizophrenia. A five-year Markov model was built form patients with schizophrenia on the stage of maintenance. Costs were taken from the perspective of the Colombian health care system (Sistema General de Seguridad Social en Salud). The effectiveness was measured in years of life under the same maintenance plan. The Markov model indicated clozapine as the as the most cost-effective alternative between the first line antipsychotics and haloperidol is it when comparing other antipsychotics. Clozapine it's the cost-effectiveness strategy among the first line of antipsychotics and haloperidol is it among the other antipsychotics. Strategies prioritizing the use of cost-effective antipsychotics could improve the resources allocation in the Colombian health care system. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Vaccine hypersensitivity--update and overview.

PubMed

Fritsche, Philipp J; Helbling, Arthur; Ballmer-Weber, Barbara K

2010-05-01

Concerns about possible reactions to vaccines or vaccinations are frequently raised. However, the rate of reported vaccine-induced adverse events is low and ranges between 4.8-83.0 per 100,000 doses of the most frequently used vaccines. The number of true allergic reactions to routine vaccines is not known; estimations range from 1 per 500,000 to 1 per 1,000,000 doses for most vaccines. When allergens such as gelatine or egg proteins are components of the formulation, the rate for serious allergic reactions may be higher. Nevertheless, anaphylactic, potentially life-threatening reactions to vaccines are still a rare event (approximately 1 per 1,500,000 doses). The variety of reported vaccine-related adverse events is broad. Most frequently, reactions to vaccines are limited to the injection site and result from a non specific activation of the inflammatory system by, for example, aluminium salts or the active microbial components. If allergy is suspected, an accurate examination followed by algorithms is the key for correct diagnosis, treatment and the decision regarding revaccination in patients with immediate-type reactions to vaccines.

Vaccines and Kawasaki disease.

PubMed

Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

2016-01-01

The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

Receipt of human papillomavirus vaccine among privately insured adult women in a U.S. Midwestern Health Maintenance Organization.

PubMed

Kharbanda, Elyse Olshen; Parker, Emily; Nordin, James D; Hedblom, Brita; Rolnick, Sharon J

2013-11-01

To describe human papillomavirus (HPV) vaccine coverage among adult privately insured women including variation in coverage by race/ethnicity. This cross-sectional, observational study included women 18-26 years of age with continuous enrollment in a U.S. Midwestern health insurance plan and at least one visit to a plan affiliated practice. Vaccination data came from insurance claims and the electronic medical record. Primary outcomes were: receipt of at least 1 HPV vaccine (HPV1) and completion of the 3-dose HPV vaccine series (HPV3). Coverage was described for the entire cohort and stratified by race/ethnicity. For a subset of women, automated data was compared to personal recall. As of June 2010, among 2546 privately insured women 18-26 years, 72.7% had received their first HPV vaccine and 57.9% completed the 3-dose series. Compared to white women, African American and Asian women had significantly lower coverage for HPV1 and HPV3. There was 94.5% (95% CI: 88.5-100%) agreement between personal recall and claims/EMR for receiving HPV1. In this cohort of privately insured women, a majority received HPV1 and more than half completed the 3-dose vaccine series. Marked disparities in receipt of HPV vaccine by race/ethnicity were observed. © 2013.

Meta-analysis comparing maintenance strategies with continuous therapy and complete chemotherapy-free interval strategies in the treatment of metastatic colorectal cancer

PubMed Central

Zhao, Lei; Wang, Jing; Li, Huihui; Che, Juanjuan; Cao, Bangwei

2016-01-01

There is as yet no consensus as to the best choice among the three treatment options (maintenance, complete chemotherapy-free intervals [CFIs], and continuous) for metastatic colorectal cancer (CRC). We performed a meta-analysis of six trials (N = 2, 454 patients) to compare the safety and efficacy of those three treatment strategies. Maintenance appeared to offer an advantage over CFI with respect to progression-free survival (PFS) (hazard ratio [HR]: 0.53, 95% confidence interval [CI], 0.40–0.69). PFS and overall survival (OS) were comparable between the maintenance and continuous strategies (HR: 1.18, 95% CI, 0.96–1.46; HR: 1.05, 95% CI, 0.98–1.27, respectively), as was OS between the maintenance and CFI strategies (HR: 0.84; 95% CI, 0.70–1.00). The incidence of grade 3/4 toxicity, including neutropenia, neuropathy, hand-foot syndrome and fatigue, was lower with maintenance than with continuous therapy. A maintenance regimen utilizing bevacizumab-based doublets appeared to confer a slight advantage over bevacizumab monotherapy with respect to PFS (P = 0.011). Maintenance appeared to reduce cumulative grade 3/4 toxicity as compared to the continuous strategy, while showing comparable efficacy. Bevacizumab-based doublets appeared to be of particular value in patients with metastatic CRC. PMID:27072579

Safety of vaccines that have been kept outside of recommended temperatures: Reports to the Vaccine Adverse Event Reporting System (VAERS), 2008-2012.

PubMed

Hibbs, Beth F; Miller, Elaine; Shi, Jing; Smith, Kamesha; Lewis, Paige; Shimabukuro, Tom T

2018-01-25

protection, and patient and parent inconvenience related to revaccination. Maintaining high vigilance, proper staff training, regular equipment maintenance, and having adequate auxiliary power are important components of comprehensive vaccine cold chain management. Published by Elsevier Ltd.

Implementing methadone maintenance treatment in prisons in Malaysia

PubMed Central

Wickersham, Jeffrey A; Marcus, Ruthanne; Kamarulzaman, Adeeba; Zahari, Muhammad Muhsin

2013-01-01

Abstract Problem In Malaysia, human immunodeficiency virus (HIV) infection is highly concentrated among people who inject opioids. For this reason, the country undertook a three-phase roll-out of a methadone maintenance treatment (MMT) programme. In Phase 3, described in this paper, MMT was implemented within prisons and retention in care was assessed. Approach After developing standard operating procedures and agreement between its Prisons Department and Ministry of Health, Malaysia established pilot MMT programmes in two prisons in the states of Kelantan (2008) and Selangor (2009) – those with the highest proportions of HIV-infected prisoners. Community-based MMT programmes were also established in Malaysia to integrate treatment activities after prisoners’ release. Local setting Having failed to reduce the incidence of HIV infection, in 2005 Malaysia embarked on a harm reduction strategy. Relevant changes Standard operating procedures were modified to: (i) escalate the dose of methadone more slowly; (ii) provide ongoing education and training for medical and correctional staff and inmates; (iii) increase the duration of methadone treatment before releasing prisoners; (iv) reinforce linkages with community MMT programmes after prisoners’ release; (v) screen for and treat tuberculosis; (vi) escalate the dose of methadone during treatment for HIV infection and tuberculosis; and (vii) optimize the daily oral dose of methadone (> 80 mg) before releasing prisoners. Lessons learnt Prison-based MMT programmes can be effectively implemented but require adequate dosing and measures are needed to improve communication between prison and police authorities, prevent police harassment of MMT clients after their release, and improve systems for tracking release dates. PMID:23554524

DNA Vaccines for Prostate Cancer

PubMed Central

Zahm, Christopher D.; Colluru, Viswa Teja; McNeel, Douglas G.

2017-01-01

DNA vaccines offer many advantages over other anti-tumor vaccine approaches due to their simplicity, ease of manufacturing, and safety. Results from several clinical trials in patients with cancer have demonstrated that DNA vaccines are safe and can elicit immune responses. However, to date few DNA vaccines have progressed beyond phase I clinical trial evaluation. Studies into the mechanism of action of DNA vaccines in terms of antigen-presenting cell types able to directly present or cross-present DNA-encoded antigens, and the activation of innate immune responses due to DNA itself, have suggested opportunities to increase the immunogenicity of these vaccines. In addition, studies into the mechanisms of tumor resistance to anti-tumor vaccination have suggested combination approaches that can increase the antitumor effect of DNA vaccines. This review focuses on these mechanisms of action and mechanisms of resistance using DNA vaccines, and how this information is being used to improve the anti-tumor effect of DNA vaccines. These approaches are then specifically discussed in the context of human prostate cancer, a disease for which DNA vaccines have been and continue to be explored as treatments. PMID:28185916

The role of complement in the success of vaccination with conjugated vs. unconjugated polysaccharide antigen.

PubMed

Salehen, Nur'ain; Stover, Cordula

2008-01-24

The complement system, a well-characterised arm of the innate immune system, significantly influences the adaptive immune response via direct cell-cell interaction and maintenance of lymphoid organ architecture. Development of vaccines is a major advance in modern health care. In this review, we highlight the importance of the marginal zone in response to both, polysaccharide and conjugated vaccines, and discuss the relevance of complement herein, based on findings obtained from animal models with specific deletions of certain complement components and from vaccination reports of complement-deficient individuals. We conclude that both, intactness of the complement system and maturity of expression of its components, are relatively more important to aid in the immune response to polysaccharide vaccine than to conjugated vaccines.

DNA vaccines in veterinary use

PubMed Central

Redding, Laurel; Werner, David B

2015-01-01

DNA vaccines represent a new frontier in vaccine technology. One important application of this technology is in the veterinary arena. DNA vaccines have already gained a foothold in certain fields of veterinary medicine. However, several important questions must be addressed when developing DNA vaccines for animals, including whether or not the vaccine is efficacious and cost effective compared with currently available options. Another important question to consider is how to apply this developing technology in a wide range of different situations, from the domestic pet to individual fish in fisheries with several thousand animals, to wildlife programs for disease control. In some cases, DNA vaccines represent an interesting option for vaccination, while in others, currently available options are sufficient. This review will examine a number of diseases of veterinary importance and the progress being made in DNA vaccine technology relevant to these diseases, and we compare these with the conventional treatment options available. PMID:19722897

Modification and Validation of the Treatment Self Regulation Questionnaire to Assess Parental Motivation for HPV Vaccination of Adolescents

PubMed Central

Denman, Deanna C.; Baldwin, Austin S.; Marks, Emily G.; Lee, Simon C.; Tiro, Jasmin A.

2016-01-01

Background According to Self-Determination Theory, the extent to which the motivation underlying behavior is self-determined or controlled influences its sustainability. This is particularly relevant for behaviors that must be repeated, such as completion of the human papillomavirus (HPV) vaccine series. To date, no measures of motivation for HPV vaccination have been developed. Methods As part of a larger study, parents (N=223) whose adolescents receive care at safety-net clinics completed a telephone questionnaire about HPV and the vaccine. We modified the Treatment Self-Regulation Questionnaire to assess parents’ motivation for HPV vaccination in both Spanish and English. We used confirmatory factor analysis to test a three-factor measurement model. Results The three-factor model fit the data well (RMSEA=.04, CFI=.98, TLI=.96), and the scales’ reliabilities were adequate (autonomous: α=.87; introjected: α=.72; external: α=.72). The factor loading strength for one item was stronger for Spanish- than English-speaking participants (p<.05); all others were equivalent. The intercorrelations among the scales ranged from −.17 to .32, suggesting discriminant factors. The scales displayed the expected pattern of correlations with other psychosocial determinants of behavior. Vaccination intentions showed a strong correlation with autonomous motivation (r= .52), but no correlation with external motivation (r=.02), suggesting autonomous motivation may be particularly important in vaccine decision-making. Conclusion Findings support the use of three subscales to measure motivation in HPV vaccination and suggest possible cultural differences in motivation. PMID:27595447

Maintenance and Intensification of Bivalent Oral Poliovirus Vaccine Use Prior to its Coordinated Global Cessation

PubMed Central

Tebbens, Radboud J Duintjer; Hampton, Lee M; Wassilak, Steven G F; Pallansch, Mark A; Cochi, Stephen L; Thompson, Kimberly M

2017-01-01

Objective To examine the impact of different bivalent oral poliovirus vaccine (bOPV) supplemental immunization activity (SIA) strategies on population immunity to serotype 1 and 3 poliovirus transmission and circulating vaccine-derived poliovirus (cVDPV) risks before and after globally-coordinated cessation of serotype 1 and 3 oral poliovirus vaccine (OPV13 cessation). Methods We adapt mathematical models that previously informed vaccine choices ahead of the trivalent oral poliovirus vaccine to bOPV switch to estimate the population immunity to serotype 1 and 3 poliovirus transmission needed at the time of OPV13 cessation to prevent subsequent cVDPV outbreaks. We then examine the impact of different frequencies of SIAs using bOPV in high risk populations on population immunity to serotype 1 and 3 transmission, on the risk of serotype 1 and 3 cVDPV outbreaks, and on the vulnerability to any imported bOPV-related polioviruses. Results Maintaining high population immunity to serotype 1 and 3 transmission using bOPV SIAs significantly reduces 1) the risk of outbreaks due to imported serotype 1 and 3 viruses, 2) the emergence of indigenous cVDPVs before or after OPV13 cessation, and 3) the vulnerability to bOPV-related polioviruses in the event of non-synchronous OPV13 cessation or inadvertent bOPV use after OPV13 cessation. Conclusion Although some reduction in global SIA frequency can safely occur, countries with suboptimal routine immunization coverage should each continue to conduct at least one annual SIA with bOPV, preferably more, until global OPV13 cessation. Preventing cVDPV risks after OPV13 cessation requires investments in bOPV SIAs now through the time of OPV13 cessation. PMID:28690915

Factors associated with ongoing criminal engagement while in opioid maintenance treatment.

PubMed

Stavseth, Marianne Riksheim; Røislien, Jo; Bukten, Anne; Clausen, Thomas

2017-06-01

This study examines factors associated with criminal engagement among patients in opioid maintenance treatment (OMT). Questionnaire data recorded annually among 5654 patients in the Norwegian OMT programme between 2005 and 2010 from seven regional treatment centres were available for analyses. Each patient answered approximately 4 times (mean: 4.11, SD: 1.46) generating a total of 18,538 questionnaires. The outcome variable of the study, engagement in criminal activity, was defined as whether a patient had been arrested, put in custody, been charged and/or convicted of a crime within the last 12months prior to the completion of the questionnaire. Three types of covariates were included: demographical, psychosocial and drug use-related. Missing data were imputed using Multivariate Imputation by Chained Equations and regression parameters were estimated by Generalized Estimation Equations to account for correlated measurements. Having a full-time job (aOR: 0.47, CI: 0.34-0.64) or being a student/having a part-time job (aOR: 0.72, CI: 0.59-0.88) was negatively associated with ongoing criminal involvement, as did having a stable living situation (aOR: 0.70, CI: 0.57-0.87). On the other hand, being male (aOR: 1.83, CI: 1.59-2.10), younger (aOR: 0.96, CI: 0.95-0.97) and using illicit drugs regularly (aOR: 3.00, CI: 2.56-3.52) was positively associated with ongoing criminal activity while in OMT. Stable accommodation and participation in meaningful daily activity was found to be protective in terms of ongoing criminal engagement. Focus on these modifiable, psychosocial factors should therefore be an important and integral aspect of opioid maintenance treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Randomized, multicenter study: on-demand versus continuous maintenance treatment with esomeprazole in patients with non-erosive gastroesophageal reflux disease.

PubMed

Bayerdörffer, Ekkehard; Bigard, Marc-Andre; Weiss, Werner; Mearin, Fermín; Rodrigo, Luis; Dominguez Muñoz, Juan Enrique; Grundling, Hennie; Persson, Tore; Svedberg, Lars-Erik; Keeling, Nanna; Eklund, Stefan

2016-04-14

Most patients with gastroesophageal reflux disease experience symptomatic relapse after stopping acid-suppressive medication. The aim of this study was to compare willingness to continue treatment with esomeprazole on-demand versus continuous maintenance therapy for symptom control in patients with non-erosive reflux disease (NERD) after 6 months. This multicenter, open-label, randomized, parallel-group study enrolled adults with NERD who were heartburn-free after 4 weeks' treatment with esomeprazole 20 mg daily. Patients received esomeprazole 20 mg daily continuously or on-demand for 6 months. The primary variable was discontinuation due to unsatisfactory treatment. On-demand treatment was considered non-inferior if the upper limit of the one-sided 95 % confidence interval (CI) for the difference between treatments was <10 %. Of 877 patients enrolled, 598 were randomized to maintenance treatment (continuous: n = 297; on-demand: n = 301). Discontinuation due to unsatisfactory treatment was 6.3 % for on-demand and 9.8 % for continuous treatment (difference -3.5 % [90 % CI: -7.1 %, 0.2 %]). In total, 82.1 and 86.2 % of patients taking on-demand and continuous therapy, respectively, were satisfied with the treatment of heartburn and regurgitation symptoms, a secondary variable (P = NS). Mean study drug consumption was 0.41 and 0.91 tablets/day, respectively. Overall, 5 % of the on-demand group developed reflux esophagitis versus none in the continuous group (P < 0.0001). The Gastrointestinal Symptom Rating Scale Reflux dimension was also improved for continuous versus on-demand treatment. Esomeprazole was well tolerated. In terms of willingness to continue treatment, on-demand treatment with esomeprazole 20 mg was non-inferior to continuous maintenance treatment and reduced medication usage in patients with NERD who had achieved symptom control with initial esomeprazole treatment. ClinicalTrials.gov identifier (NCT number): NCT02670642 ; Date of registration: December

NIAID meeting report: improving malaria vaccine strategies through the application of immunological principles.

PubMed

Mo, Annie X Y; Augustine, Alison Deckhut

2014-02-26

A highly efficacious vaccine to prevent malaria infection or clinical disease is still far from reality despite several decades of intensive effort and a growing global commitment in malaria vaccine development. Further understanding of the mechanisms required for induction of effective host immune responses and maintenance of long-term protective immunity is needed to facilitate rational approaches for vaccine design and evaluation. The National Institute of Allergy and Infectious Diseases (NIAID) conducted a workshop on June 18-19, 2012 with experts in the fields of malaria vaccine development, malaria immunology, and basic immunology to address issues associated with improving our current understanding of malaria vaccine immunity. This report summarizes the discussion and major recommendations generated by the workshop participants regarding the application of recent advances in basic immunology and state-of-the-art immunological tools to improve progress and help address current challenges and knowledge gaps in malaria vaccine development. Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis.

PubMed

Tjon Pian Gi, Robin E A; San Giorgi, Michel R M; Pawlita, Michael; Michel, Angelika; van Hemel, Bettien M; Schuuring, Ed M D; van den Heuvel, Edwin R; van der Laan, Bernard F A M; Dikkers, Frederik G

2016-10-01

Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil(®)) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was measured were included. Multiplex HPV Serology was used to determine HPV-specific antibodies pre- and post-vaccination. Surgical interventions and patient records were analyzed. Five HPV6 and 1 HPV11 infected patient were included. Mean antibody reactivity against the associated HPV type rose from 1125 median fluorescence intensity (MFI) pre-vaccination to 4690 MFI post-vaccination (p < 0.001). Median post-vaccination follow-up was 4 years. Poisson regression analysis showed that the quadrivalent HPV vaccine decreased the incidence rate of surgeries. The immune system of RRP patients is able to increase antibody reactivity against the associated HPV type. A double blind randomized controlled trial is needed to determine whether this immunological increase can cause decrease in number of surgeries.

Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependence.

PubMed

Longo, Marie; Wickes, Wendy; Smout, Matthew; Harrison, Sonia; Cahill, Sharon; White, Jason M

2010-01-01

To investigate the safety and efficacy of once-daily supervised oral administration of sustained-release dexamphetamine in people dependent on methamphetamine. Randomized, double-blind, placebo-controlled trial. Forty-nine methamphetamine-dependent drug users from Drug and Alcohol Services South Australia (DASSA) clinics. Participants were assigned randomly to receive up to 110 mg/day sustained-release dexamphetamine (n = 23) or placebo (n = 26) for a maximum of 12 weeks, with gradual reduction of the study medication over an additional 4 weeks. Medication was taken daily under pharmacist supervision. Primary outcome measures included treatment retention, measures of methamphetamine consumption (self-report and hair analysis), degree of methamphetamine dependence and severity of methamphetamine withdrawal. Hair samples were analysed for methamphetamine using liquid chromatography-mass spectrometry. Treatment retention was significantly different between groups, with those who received dexamphetamine remaining in treatment for an average of 86.3 days compared with 48.6 days for those receiving placebo (P = 0.014). There were significant reductions in self-reported methamphetamine use between baseline and follow-up within each group (P < 0.0001), with a trend to a greater reduction among the dexamphetamine group (P = 0.086). Based on hair analysis, there was a significant decrease in methamphetamine concentration for both groups (P < 0.0001). At follow-up, degree of methamphetamine dependence was significantly lower in the dexamphetamine group (P = 0.042). Dexamphetamine maintenance was not associated with serious adverse events. The results of this preliminary study have demonstrated that a maintenance pharmacotherapy programme of daily sustained-release amphetamine dispensing under pharmacist supervision is both feasible and safe. The increased retention in the dexamphetamine group, together with the general decreases in methamphetamine use, degree of dependence

Hexavalent IPV-based combination vaccines for public-sector markets of low-resource countries

PubMed Central

Mahmood, Kutub; Pelkowski, Sonia; Atherly, Deborah; Sitrin, Robert; Donnelly, John J

2013-01-01

In anticipation of the successful eradication of wild polio virus, alternative vaccination strategies for public-sector markets of low-resource countries are extremely important, but are still under development. Following polio eradication, inactivated polio vaccine (IPV) would be the only polio vaccine available, and would be needed for early childhood immunization for several years, as maintenance of herd immunity will be important for sustaining polio eradication. Low-cost combination vaccines containing IPV could provide reliable and continuous immunization in the post-polio eradication period. Combination vaccines can potentially simplify complex pediatric routine immunization schedules, improve compliance, and reduce costs. Hexavalent vaccines containing Diphtheria (D), Tetanus (T), whole cell pertussis (wP), Hepatitis B (HBV), Haemophilus b (Hib) and the three IPV serotype antigens have been considered as the ultimate combination vaccine for routine immunization. This product review evaluates potential hexavalent vaccine candidates by composition, probable time to market, expected cost of goods, presentation, and technical feasibility and offers suggestions for development of low-cost hexavalent combination vaccines. Because there are significant technical challenges facing wP-based hexavalent vaccine development, this review also discusses other alternative approaches to hexavalent that could also ensure a timely and reliable supply of low-cost IPV based combination vaccines. PMID:23787559

Hexavalent IPV-based combination vaccines for public-sector markets of low-resource countries.

PubMed

Mahmood, Kutub; Pelkowski, Sonia; Atherly, Deborah; Sitrin, Robert D; Donnelly, John J

2013-09-01

In anticipation of the successful eradication of wild polio virus, alternative vaccination strategies for public-sector markets of low-resource countries are extremely important, but are still under development. Following polio eradication, inactivated polio vaccine (IPV) would be the only polio vaccine available, and would be needed for early childhood immunization for several years, as maintenance of herd immunity will be important for sustaining polio eradication. Low-cost combination vaccines containing IPV could provide reliable and continuous immunization in the post-polio eradication period. Combination vaccines can potentially simplify complex pediatric routine immunization schedules, improve compliance, and reduce costs. Hexavalent vaccines containing Diphtheria (D), Tetanus (T), whole cell pertussis (wP), Hepatitis B (HBV), Haemophilus b (Hib) and the three IPV serotype antigens have been considered as the ultimate combination vaccine for routine immunization. This product review evaluates potential hexavalent vaccine candidates by composition, probable time to market, expected cost of goods, presentation, and technical feasibility and offers suggestions for development of low-cost hexavalent combination vaccines. Because there are significant technical challenges facing wP-based hexavalent vaccine development, this review also discusses other alternative approaches to hexavalent that could also ensure a timely and reliable supply of low-cost IPV based combination vaccines.

VacciCost - A tool to estimate the resource requirements for implementing livestock vaccination campaigns. Application to peste des petits ruminants (PPR) vaccination in Senegal.

PubMed

Tago, Damian; Sall, Baba; Lancelot, Renaud; Pradel, Jennifer

2017-09-01

Vaccination is one of the main tools currently available to control animal diseases. In eradication campaigns, vaccination plays a crucial role by reducing the number of susceptible hosts with the ultimate goal of interrupting disease transmission. Nevertheless, mass vaccination campaigns may be very expensive and in some cases unprofitable. VacciCost is a tool designed to help decision-makers in the estimation of the resources required to implement mass livestock vaccination campaigns against regulated diseases. The tool focuses on the operational or running costs of the campaign, so acquisition of new equipment or vehicles is not considered. It takes into account different types of production systems to differentiate the vaccination productivity (number of animals vaccinated per day) in systems where animals are concentrated and easy to reach, from those characterized by small herds that are scattered and less accessible. The resource requirements are classified in eight categories: vaccines, injection supplies, personnel, transport, maintenance and overhead, training, social mobilization, and surveillance and monitoring. This categorization allows identifying the most expensive components of a vaccination campaign, which is crucial to design cost-reduction strategies. The use of the tool is illustrated using data collected in collaboration with Senegalese Veterinary Services regarding vaccination against peste des petits ruminants. The average daily number of animals vaccinated per vaccination team was found to be crucial for the costs of the campaign so significant savings can be obtained by implementing training to improve the performance of vaccination teams. Copyright © 2017 Centre de cooperation internationale en recherche agronomique pour le developpement (CIRAD). Published by Elsevier B.V. All rights reserved.

The fish parasite Ichthyophthirius multifiliis - Host immunology, vaccines and novel treatments.

PubMed

Jørgensen, Louise von Gersdorff

2017-08-01

Ichthyophthirius multifiliis, the causative agent of white spot disease (ichthyophthiriasis) is a major burden for fish farmers and aquarists globally. The parasite infects the skin and the gills of freshwater fish, which may acquire a protective adaptive immune response against this disease, making vaccine strategies feasible. However, there is no prophylactic treatment available and repetitive treatments with auxiliary substances are needed to control the infection. Historically, a variety of drugs and chemicals have been used to combat the disease but due to changing regulations and recognition of carcinogenic and environmentally damaging effects the most efficient compounds are prohibited. A continuous search for novel substances, which are highly effective against the parasites and harmless for the fish is ongoing. These compounds should be environmentally friendly and cost-effective. This review presents recent progress within host immunology, vaccinology and a description of novel substances, which have been tested as treatments against ichthyophthiriasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of human papillomavirus vaccines in cervical cancer: Prevention and treatment.

PubMed

Bogani, Giorgio; Leone Roberti Maggiore, Umberto; Signorelli, Mauro; Martinelli, Fabio; Ditto, Antonino; Sabatucci, Ilaria; Mosca, Lavinia; Lorusso, Domenica; Raspagliesi, Francesco

2018-02-01

Human papillomavirus (HPV) is the most common sexually transmitted disease, worldwide. Primary prevention thorough vaccination si able to reduce the burden of HPV-related lesions. Ten years ago the Food and drug Administration (FDA) approved the first vaccine against HPV. In the last decades, growing data on safety and effectiveness have been collected. In the present review we report the current knowledge on vaccine against HPV, highlighting the current value and prospective regarding the widespread diffusion of HPV vaccines. The role of emerging therapeutic vaccines is reviewed. Copyright © 2017 Elsevier B.V. All rights reserved.

Drug versus vaccine investment: a modelled comparison of economic incentives

PubMed Central

2013-01-01

Background Investment by manufacturers in research and development of vaccines is relatively low compared with that of pharmaceuticals. If current evaluation technologies favour drugs over vaccines, then the vaccines market becomes relatively less attractive to manufacturers. Methods We developed a mathematical model simulating the decision-making process of regulators and payers, in order to understand manufacturers’ economic incentives to invest in vaccines rather than curative treatments. We analysed the objectives and strategies of manufacturers and payers when considering investment in technologies to combat a disease that affects children, and the interactions between them. Results The model confirmed that, for rare diseases, the economically justifiable prices of vaccines could be substantially lower than drug prices, and that, for diseases spread across multiple cohorts, the revenues derived from vaccinating one cohort per year (routine vaccination) could be substantially lower than those generated by treating sick individuals. Conclusions Manufacturers may see higher incentives to invest in curative treatments rather than in routine vaccines. To encourage investment in vaccines, health authorities could potentially revise their incentive schemes by: (1) committing to vaccinate all susceptible cohorts in the first year (catch-up campaign); (2) choosing a long-term horizon for health technology evaluation; (3) committing higher budgets for vaccines than for treatments; and (4) taking into account all intangible values derived from vaccines. PMID:24011090

Cost-effectiveness of HPV vaccination in Belize.

PubMed

Walwyn, Leslie; Janusz, Cara Bess; Clark, Andrew David; Prieto, Elise; Waight, Eufemia; Largaespada, Natalia

2015-05-07

Among women in Belize, cervical cancer is both the leading cancer and the leading cause of cancer deaths. Both the quadrivalent and bivalent human papillomavirus (HPV) vaccines are licensed in Belize. The Ministry of Health of Belize convened a multidisciplinary team to estimate the costs, health benefits, and cost-effectiveness of adding an HPV vaccine to the national immunization schedule. The CERVIVAC cost-effectiveness model (Version 1.123) was used to assess the lifetime health and economic outcomes of vaccinating one cohort of girls aged 10 years against HPV. The comparator was no HPV vaccination. The PAHO Revolving Fund negotiated price of US$ 13.79 per dose was used (for the quadrivalent vaccine) and national data sources were used to define demography, cervical cancer incidence and mortality, cervical cancer treatment costs, and vaccine delivery costs. Estimates from international agencies were used in scenario analysis. In a cohort of ∼4000 Belizean girls tracked over a lifetime, HPV vaccination is estimated to prevent 69 new cases of cervical cancer (undiscounted), and 51 cervical cancer deaths (undiscounted). Considering the potential cervical cancer treatment costs and lost wages avoided by households (societal perspective), the cost per disability-adjusted life year (DALY) averted was estimated to be US$ 429. This increased to US$ 1320 when cervical cancer treatment costs and lost wages were excluded from the analysis. Both estimates are far below the gross domestic product (GDP) per capita of Belize (US$ 4795). The lifetime health care costs saved by the women and their families represent more than 60% of the investment cost needed by the Government for the vaccine. Routine HPV vaccination would be highly cost-effective in Belize. If affordable, efforts should be made to expedite the introduction of this vaccine into the Belizean national immunization program. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antiviral Innate Immune Activation in HIV-Infected Adults Negatively Affects H1/IC31-Induced Vaccine-Specific Memory CD4+ T Cells

PubMed Central

Schindler, Tobias; Kagina, Benjamin M.; Zhang, Jitao David; Lukindo, Tedson; Mpina, Maxmillian; Bang, Peter; Kromann, Ingrid; Hoff, Søren T.; Andersen, Peter; Reither, Klaus; Churchyard, Gavin J.; Certa, Ulrich

2015-01-01

Tuberculosis (TB) remains a global health problem, with vaccination being a necessary strategy for disease containment and elimination. A TB vaccine should be safe and immunogenic as well as efficacious in all affected populations, including HIV-infected individuals. We investigated the induction and maintenance of vaccine-induced memory CD4+ T cells following vaccination with the subunit vaccine H1/IC31. H1/IC31 was inoculated twice on study days 0 and 56 among HIV-infected adults with CD4+ lymphocyte counts of >350 cells/mm3. Whole venous blood stimulation was conducted with the H1 protein, and memory CD4+ T cells were analyzed using intracellular cytokine staining and polychromatic flow cytometry. We identified high responders, intermediate responders, and nonresponders based on detection of interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) expressing central (TCM) and effector memory CD4+ T cells (TEM) 182 days after the first immunization. Amplicon-based transcript quantification using next-generation sequencing was performed to identify differentially expressed genes that correlated with vaccine-induced immune responses. Genes implicated in resolution of inflammation discriminated the responders from the nonresponders 3 days after the first inoculation. The volunteers with higher expression levels of genes involved in antiviral innate immunity at baseline showed impaired H1-specific TCM and TEM maintenance 6 months after vaccination. Our study showed that in HIV-infected volunteers, expression levels of genes involved in the antiviral innate immune response affected long-term maintenance of H1/IC31 vaccine-induced cellular immunity. (The clinical trial was registered in the Pan African Clinical Trials Registry [PACTR] with the identifier PACTR201105000289276.) PMID:25924764

EVALUATION OF TYPHOID VACCINES IN THE LABORATORY AND IN A CONTROLLED FIELD TRIAL IN POLAND. PRELIMINARY REPORT.

PubMed

BLAKE, J B

1965-01-01

In 1961 a controlled field trial of anti-typhoid vaccines was carried out in 25 regions in Poland. Four types of vaccine were studied: (1) bacterial acetone-killed and -dried vaccine (two kinds), (2) bacterial formol-killed phenol-preserved vaccine, (3) Westphal's endotoxin adsorbed on aluminium hydroxide, and (4) Grasset's vaccine (autolysate of typhoid bacilli adsorbed on aluminium hydroxide). The control vaccine was tetanus toxoid. A total of 690 655 persons received two inoculations. Prior to the field trial, laboratory tests were carried out on the vaccines, postvaccinal reactions were studied, and a serological examination was made of randomly selected blood samples. The vaccination was followed by a two-year survey of cases of typhoid and other diseases. Among children aged 5-14 years, the formol-killed phenol-preserved vaccine was found to be the most effective and Grasset's vaccine the least. Among adults aged 15-60 years, no conclusive evidence for the effectiveness of the vaccines could be obtained owing to the small number of cases. This may be due to the maintenance of immunity through repeated annual vaccination with bacterial vaccines.

The impact of deposition site on vaccination efficiency of a live bacterial poultry vaccine.

PubMed

Evans, J D; Leigh, S A; Purswell, J L; Collier, S D; Kim, E J; Boykin, D L; Branton, S L

2015-08-01

Vaccines are utilized within the poultry industry to minimize disease-associated losses and spray vaccination is a commonly utilized means for the mass application of poultry vaccines. During this process, vaccine-laden particles are deposited upon target areas (e.g., eyes, nares, and oral cavity) resulting in the direct internalization of the vaccine. However, particles are also deposited on nontarget areas such as the exterior of the subject and its surrounding environment. To better determine the fate of particles deposited upon nontarget areas and the impact of deposition site on the efficiency of vaccine application, a live bacterial poultry vaccine (AviPro(®) MG F) was applied via spray using a spray cabinet with a slotted partition allowing for head-only, body-only, and whole-bird spray application. At 11 wk age, Hy-Line(®) W-36 pullets (n = 280) were allocated equally among 7 treatments including: nonvaccinated controls, pullets spray-vaccinated at the manufacturer's recommended dose (1X) in a site-specific manner (head-only, body-only, and whole-bird), pullets spray-vaccinated at 5X the recommended level (body-only), pullets vaccinated by manual eye-drop application (1X), and pullets eye-drop vaccinated at a level approximating that achieved during the spray vaccination process (1/700X). At 6 to 7 wk postvaccination, vaccination efficiency was assessed via serological-based assays [serum plate agglutination (SPA) and ELISA] and the detection of vaccine-derived in vivo populations. Results indicate an additive contribution of the vaccine deposited on the body to the overall vaccination efficiency of this live bacterial live poultry vaccine. © 2015 Poultry Science Association Inc.

Manufacturing DTaP-based combination vaccines: industrial challenges around essential public health tools.

PubMed

Vidor, Emmanuel; Soubeyrand, Benoit

2016-12-01

The manufacture of DTP-backboned combination vaccines is complex, and vaccine quality is evaluated by both batch composition and conformance of manufacturing history. Since their first availability, both the manufacturing regulations for DTP combination vaccines and their demand have evolved significantly. This has resulted in a constant need to modify manufacturing and quality control processes. Areas covered: Regulations that govern the manufacture of complex vaccines can be inconsistent between countries and need to be aligned with the regulatory requirements that apply in all countries of distribution. Changes in product mix and quantities can lead to uncertainty in vaccine supply maintenance. These problems are discussed in the context of the importance of these products as essential public health tools. Expert commentary: Increasing demand for complex vaccines globally has led to problems in supply due to intrinsically complex manufacturing and regulatory procedures. Vaccine manufacturers are fully engaged in the resolution of these challenges, but currently changes in demand need ideally to be anticipated approximately 3 years in advance due to long production cycle times.

Semiconductor diode laser device adjuvanting intradermal vaccine

PubMed Central

Kimizuka, Yoshifumi; Callahan, John J.; Huang, Zilong; Morse, Kaitlyn; Katagiri, Wataru; Shigeta, Ayako; Bronson, Roderick; Takeuchi, Shu; Shimaoka, Yusuke; Chan, Megan P. K.; Zeng, Yang; Li, Binghao; Chen, Huabiao; Tan, Rhea Y. Y.; Dwyer, Conor; Mulley, Tyler; Leblanc, Pierre; Goudie, Calum; Gelfand, Jeffrey; Tsukada, Kosuke; Brauns, Timothy; Poznansky, Mark C.; Bean, David; Kashiwagi, Satoshi

2017-01-01

A brief exposure of skin to a low-power, non-tissue damaging laser light has been demonstrated to augment immune responses to intradermal vaccination. Both preclinical and clinical studies show that this approach is simple, effective, safe and well tolerated compared to standard chemical or biological adjuvants. Until now, these laser exposures have been performed using a diode-pumped solid-state laser (DPSSL) devices, which are expensive and require labor-intensive maintenance and special training. Development of an inexpensive, easy-to-use and small device would form an important step in translating this technology toward clinical application Here we report that we have established a handheld, near-infrared (NIR) laser device using semiconductor diodes emitting either 1061, 1258, or 1301 nm light that costs less than $4,000, and that this device replicates the adjuvant effect of a DPSSL system in a mouse model of influenza vaccination. Our results also indicate that a broader range of NIR laser wavelengths possess the ability to enhance vaccine immune responses, allowing engineering options for the device design. This small, low-cost device establishes the feasibility of using a laser adjuvant approach for mass-vaccination programs in a clinical setting, opens the door for broader testing of this technology with a variety of vaccines and forms the foundation for development of devices ready for use in the clinic. PMID:28365253

Semiconductor diode laser device adjuvanting intradermal vaccine.

PubMed

Kimizuka, Yoshifumi; Callahan, John J; Huang, Zilong; Morse, Kaitlyn; Katagiri, Wataru; Shigeta, Ayako; Bronson, Roderick; Takeuchi, Shu; Shimaoka, Yusuke; Chan, Megan P K; Zeng, Yang; Li, Binghao; Chen, Huabiao; Tan, Rhea Y Y; Dwyer, Conor; Mulley, Tyler; Leblanc, Pierre; Goudie, Calum; Gelfand, Jeffrey; Tsukada, Kosuke; Brauns, Timothy; Poznansky, Mark C; Bean, David; Kashiwagi, Satoshi

2017-04-25

A brief exposure of skin to a low-power, non-tissue damaging laser light has been demonstrated to augment immune responses to intradermal vaccination. Both preclinical and clinical studies show that this approach is simple, effective, safe and well tolerated compared to standard chemical or biological adjuvants. Until now, these laser exposures have been performed using a diode-pumped solid-state laser (DPSSL) devices, which are expensive and require labor-intensive maintenance and special training. Development of an inexpensive, easy-to-use and small device would form an important step in translating this technology toward clinical application. Here we report that we have established a handheld, near-infrared (NIR) laser device using semiconductor diodes emitting either 1061, 1258, or 1301nm light that costs less than $4000, and that this device replicates the adjuvant effect of a DPSSL system in a mouse model of influenza vaccination. Our results also indicate that a broader range of NIR laser wavelengths possess the ability to enhance vaccine immune responses, allowing engineering options for the device design. This small, low-cost device establishes the feasibility of using a laser adjuvant approach for mass-vaccination programs in a clinical setting, opens the door for broader testing of this technology with a variety of vaccines and forms the foundation for development of devices ready for use in the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

Military Infectious Diseases Update on Vaccine Development

DTIC Science & Technology

2011-01-24

Research Program (MIDRP) Insect Vector ControlDiagnostics Prevention Treatment Infectious diseases adversely impact military operations. Vaccines...appropriate treatment and aids commanders in the field. Most militarily relevant infectious diseases are transmitted by biting insects and other...based Insect Repellent (1946) Vaccines Protectants Antiparasitic Drugs Research Effort Advanced Development Fielded Products Malaria Rapid

Antibody response and protective immunity of chickens vaccinated with booster dose of recombinant oil-adjuvanted Leucocytozoon caulleryi subunit vaccine.

PubMed

Umali, Dennis V; Ito, Akira; Del Valle, Fletcher P; Shirota, Kazutoshi; Katoh, Hiromitsu

2014-12-01

Leucocytozoon caulleryi is an economically important poultry pathogen that causes subclinical to fatal disease in chickens. Because of limited preventive and treatment options against this disease, an oil-adjuvanted recombinant vaccine (O-rR7) targeting the R7 protein of L. caulleryi second-generation schizonts was developed. Different vaccination programs, namely, single vaccination at 45 days (0.1-ml dose), single vaccination at 130 days (0.25 ml), and initial vaccination at 45 days (0.1 ml) followed by a booster dose at 130 days (0.25 ml) were explored to compare the effects of single and booster vaccination on antibody response, duration of protective immunity, and degree of clinical signs after experimental L. caulleryi infection. Of the three treatments groups, initial vaccination at 45 days followed by a booster vaccination at 130 days of age resulted to rapid increase in antibody titers, which persisted for up to 182 days. Antibody titers reached peak values 35 days and 14 days after initial and booster vaccination, respectively. In comparison, single vaccination at 45 days of age resulted in production of antibodies above 1600 ELISA units for 56 days postvaccination, and single vaccination at 130 days of age produced peak antibody titers 35 days postvaccination, which remained above 1600 ELISA units for 126 days. Experimental infection of L. caulleryi at 256 days, when antibody titers had waned, did not result to severe clinical disease in chickens that received booster vaccination, whereas mild to severe disease was observed in chickens that received a single vaccination. Evaluation of immune response at 15 and 21 days postinfection showed that chickens that received booster vaccination had a twofold increase (P < 0.01) in antibody titers as compared to those receiving a single vaccination. Administering booster shots of O-rR7 is therefore recommended, especially in farms located in areas where Leucocytozoon is endemic.

miR-125b-1 and miR-378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer.

PubMed

Tanaka, Hironori; Hazama, Shoichi; Iida, Michihisa; Tsunedomi, Ryouichi; Takenouchi, Hiroko; Nakajima, Masao; Tokumitsu, Yukio; Kanekiyo, Shinsuke; Shindo, Yoshitaro; Tomochika, Shinobu; Tokuhisa, Yoshihiro; Sakamoto, Kazuhiko; Suzuki, Nobuaki; Takeda, Shigeru; Yamamoto, Shigeru; Yoshino, Shigefumi; Ueno, Tomio; Hamamoto, Yoshihiko; Fujita, Yusuke; Tanaka, Hiroaki; Tahara, Ko; Shimizu, Ryoichi; Okuno, Kiyotaka; Fujita, Koji; Kuroda, Masahiko; Nakamura, Yusuke; Nagano, Hiroaki

2017-11-01

Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse-transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells (P = 0.040), and miR-378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001). Multivariate analysis showed that expression of miR-378a in stromal cells was the best among the three predictors (HR, 2.730; 95% CI, 1.027-7.585; P = 0.044). In conclusion, miR-125b-1 and miR-378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

The future potential for cocaine vaccines.

PubMed

Orson, Frank M; Wang, Rongfu; Brimijoin, Stephen; Kinsey, Berma M; Singh, Rana Ak; Ramakrishnan, Muthu; Wang, Helen Y; Kosten, Thomas R

2014-09-01

Addiction to cocaine is a major problem around the world, but especially in developed countries where the combination of wealth and user demand has created terrible social problems. Although only some users become truly addicted, those who are often succumb to a downward spiral in their lives from which it is very difficult to escape. From the medical perspective, the lack of effective and safe, non-addictive therapeutics has instigated efforts to develop alternative approaches for treatment, including anticocaine vaccines designed to block cocaine's pharmacodynamic effects. This paper discusses the implications of cocaine pharmacokinetics for robust vaccine antibody responses, the results of human vaccine clinical trials, new developments in animal models for vaccine evaluation, alternative vaccine formulations and complementary therapy to enhance anticocaine effectiveness. Robust anti-cocaine antibody responses are required for benefit to cocaine abusers, but since any reasonably achievable antibody level can be overcome with higher drug doses, sufficient motivation to discontinue use is also essential so that the relative barrier to cocaine effects will be appropriate for each individual. Combining a vaccine with achievable levels of an enzyme to hydrolyze cocaine to inactive metabolites, however, may substantially increase the blockade and improve treatment outcomes.

Modification and validation of the Treatment Self Regulation Questionnaire to assess parental motivation for HPV vaccination of adolescents.

PubMed

Denman, Deanna C; Baldwin, Austin S; Marks, Emily G; Lee, Simon C; Tiro, Jasmin A

2016-09-22

According to Self-Determination Theory, the extent to which the motivation underlying behavior is self-determined or controlled influences its sustainability. This is particularly relevant for behaviors that must be repeated, such as completion of the human papillomavirus (HPV) vaccine series. To date, no measures of motivation for HPV vaccination have been developed. As part of a larger study, parents (N=223) whose adolescents receive care at safety-net clinics completed a telephone questionnaire about HPV and the vaccine. We modified the Treatment Self-Regulation Questionnaire to assess parents' motivation for HPV vaccination in both Spanish and English. We used confirmatory factor analysis to test a three-factor measurement model. The three-factor model fit the data well (RMSEA=0.04, CFI=0.98, TLI=0.96), and the scales' reliabilities were adequate (autonomous: α=0.87; introjected: α=0.72; external: α=0.72). The factor loading strength for one item was stronger for Spanish- than English-speaking participants (p<0.05); all others were equivalent. The intercorrelations among the scales ranged from -0.17 to 0.32, suggesting discriminant factors. The scales displayed the expected pattern of correlations with other psychosocial determinants of behavior. Vaccination intentions showed a strong correlation with autonomous motivation (r=0.52), but no correlation with external motivation (r=0.02), suggesting autonomous motivation may be particularly important in vaccine decision-making. Findings support the use of three subscales to measure motivation in HPV vaccination and suggest possible cultural differences in motivation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vaccinations-Between free will and coercion.

PubMed

Patryn, Rafał K; Zagaja, Anna

2016-08-02

Dynamically changing social situation associated with migrations, increasing freedom rights, popularity of anti-vaccine movements and the resulting from that decrease in herd immunity, forces the medical society and the governments of various countries to reflect on the attitude toward vaccinations. Issues of freedoms and self-determination frequently do not accept any medical coercion in case of prophylactic vaccinations, however, recent waves of epidemics revealed that there is a necessity for undertaking strict legal actions to encourage vaccinations. After analyzing various legal approaches toward vaccinations we believe that personal coercion in case of vaccination refusal has too far reaching sanctions and propose the possibility of balancing the right to autonomy and the medical coercion. We postulate that vaccination refusal should be equivalent with covering frequently high medical costs in case of infection, The threat of financing medical treatment should influence the decision making process of those opposing vaccinations simultaneously respecting their rights not too get vaccinated.

Differing antidepressant maintenance methodologies.

PubMed

Safer, Daniel J

2017-10-01

The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

Therapeutic vaccines in renal cell carcinoma.

PubMed

Schwaab, Thomas; Ernstoff, Marc S

2011-07-01

Metastatic renal cell carcinoma (mRCC) is a lethal disease. The advent of tyrosine kinase inhibitors (TKIs) has changed the disease process, yet the majority of patients will develop treatment-resistant disease. IL-2 based immunotherapy in mRCC is the only US FDA-approved treatment with curative results. Immunotherapeutic vaccine approaches to mRCC have been under investigation for several decades with mixed results. The recent FDA-approval of the first cellular immunotherapy in prostate cancer (Provenge(®)) has reinvigorated the search for similar vaccines approaches in mRCC. This review introduces the concepts and different features required for a successful anticancer vaccine approach.

Ebolavirus Vaccines for Humans and Apes

PubMed Central

Fausther-Bovendo, Hugues; Mulangu, Sabue

2012-01-01

Due to high case fatality proportions, person-to-person transmission, and potential use in bioterrorism, the development of a vaccine against ebolavirus remains a top priority. Although no licensed vaccine or treatment against ebolavirus is currently available, progress in preclinical testing of countermeasures has been made. Here, we will review ebolavirus vaccine candidates and considerations for their use in humans and wild apes. PMID:22560007

Therapeutic vaccines for leishmaniasis.

PubMed

Khamesipour, Ali

2014-11-01

Numerous therapeutic strategies are used to treat leishmaniasis. The treatment of cutaneous leishmaniasis (CL) is solely depends on antimonate derivatives with safety issues and questionable efficacy and there is no fully effective modality to treat CL caused by Leishmania tropica and Leishmania braziliensis. There is no prophylactic vaccine available against any form of leishmaniasis. Immunotherapy for CL has a long history; immunotherapy trials of first and second generation vaccines showed promising results. The current article briefly covers the prophylactic vaccines and explains different immunotherapy strategies that have been used to treat leishmaniasis. This paper does not include experimental vaccines and only lays emphasis on human trials and those vaccines which reached human trials. Immunotherapy is currently used to successfully treat several disorders; Low cost, limited side effects and no possibility to develop resistance make immunotherapy a valuable choice especially for infectious disease with chemotherapy problems. Efforts are needed to explore the immunological surrogate marker(s) of cure and protection in leishmaniasis and overcome the difficulties in standardization of crude Leishmania vaccines. One of the reasons for anti-leishmaniasis vaccine failure is lack of an appropriate adjuvant. So far, not enough attention has been paid to develop vaccines for immunotherapy of leishmaniasis.

Double-Blind 18-Month Trial of Lithium Versus Divalproex Maintenance Treatment in Pediatric Bipolar Disorder.

ERIC Educational Resources Information Center

Findling, Robert L.; McNamara, Nora K.; Youngstrom, Eric A.; Stansbrey, Robert; Gracious, Barbara L.; Reed, Michael D.; Calabrese, Joseph R.

2005-01-01

Objective: To determine whether divalproex sodium (DVPX) was superior to lithium carbonate ([Li.sup.+]) in the maintenance monotherapy treatment of youths diagnosed with bipolar disorder who had been previously stabilized on combination [Li.sup.+] and DVPX ([Li.sup.+]/DVPX) pharmacotherapy. Method: Youths ages 5-17 years with bipolar I or II…

Haemophilus influenzae type b meningitis in a vaccinated and immunocompetent child.

PubMed

Almeida, Ana F; Trindade, Eunice; B Vitor, Artur; Tavares, Margarida

Invasive Haemophilus influenzae type b (Hib) disease decreased dramatically after the introduction of conjugate vaccine in routine immunization schedules. We report a case of a fifteen-months-old girl, previously healthy and vaccinated, admitted in the emergency room with fever and vomiting. She was irritable and the Brudzinski's sign was positive. The cerebrospinal fluid (CSF) analysis showed pleocytosis and high protein level. Empiric intravenous antibiotics (ceftriaxone and vancomycin) were administered for suspected bacterial meningitis during 10 days. Serotyping of the Haemophilus influenzae strain found in CSF revealed a serotype b. After one year of follow-up no Hib meningitis sequelae were noted. Despite vaccination compliance and absence of risk factors, invasive Hib disease can occur due to vaccine failure. Efforts to keep the low incidence of invasive Hib disease should be directed to the maintenance of high vaccination coverage rates, combined with the notification and surveillance strategies already implemented in each country. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Substance abuse vaccines.

PubMed

Orson, Frank M; Kinsey, Berma M; Singh, Rana A K; Wu, Yan; Gardner, Tracie; Kosten, Thomas R

2008-10-01

Conventional substance-abuse treatments have only had limited success for drugs such as cocaine, nicotine, methamphetamine, and phencyclidine. New approaches, including vaccination to block the effects of these drugs on the brain, are in advanced stages of development. Although several potential mechanisms for the effects of antidrug vaccines have been suggested, the most straightforward and intuitive mechanism involves binding of the drug by antibodies in the bloodstream, thereby blocking entry and/or reducing the rate of entry of the drug into the central nervous system. The benefits of such antibodies on drug pharmacodynamics will be influenced by both the quantitative and the qualitative properties of the antibodies. The sum of these effects will determine the success of the clinical applications of antidrug vaccines in addiction medicine. This review will discuss these issues and present the current status of vaccine development for nicotine, cocaine, methamphetamine, phencyclidine, and morphine.

Hookworm vaccines: past, present, and future.

PubMed

Loukas, Alex; Bethony, Jeffrey; Brooker, Simon; Hotez, Peter

2006-11-01

Hookworms are gastrointestinal nematodes that infect almost 1 billion people in developing countries. The main clinical symptom of human hookworm infections is iron-deficiency anaemia, a direct consequence of the intestinal blood loss resulting from the parasite's feeding behaviour. Although treatment is available and currently used for the periodic removal of adult hookworms from patients, this approach has not effectively controlled hookworm in areas of rural poverty. Furthermore, treated individuals remain susceptible to reinfection following exposure to third-stage infective hookworm larvae in the soil as early as 4-12 months after drug treatment. Therefore, a prophylactic vaccine against hookworm infection would provide an attractive additional tool for the public-health control of this disease. The feasibility of developing a vaccine is based on the previous success of an attenuated larval vaccine against canine hookworm. Several laboratory and field studies have explored the development of a human anti-hookworm vaccine, describing potential protective mechanisms and identifying candidate antigens, one of which is now in clinical trials. The current roadmap that investigators have conceived has been influenced by vaccine development for blood-feeding nematodes of livestock and companion animals; however, recombinant vaccines have yet to be developed for nematodes that parasitise animals or human beings. The roadmap also addresses the obstacles facing development of a vaccine for developing countries, where there is no commercial market.

HIV vaccine trials: will intravenous drug users enroll?

PubMed Central

Meyers, K; Metzger, D S; Navaline, H; Woody, G E; McLellan, A T

1994-01-01

OBJECTIVES. The purpose of this study was to assess the willingness of intravenous drug users to participate in a preventive human immunodeficiency virus (HIV) vaccine efficacy trial. METHODS. Of the 347 intravenous drug users in methadone treatment who were approached for participation, 257 completed a battery of self-administered questionnaires assessing risk behaviors, interest in vaccine trials, and other vaccine-related information. Data from 16 known seropositives and 1 inconsistent responder were dropped from analyses (n = 240). RESULTS. Fifty-two percent of the subjects expressed a willingness to be one of the first individuals to participate in a preventive HIV vaccine efficacy trial. Subjects who had recently shared needles or works and subjects who trusted the government to ensure vaccine safety were both twice as likely to report interest in participation. Twenty-two percent of subjects reported that they would increase needle sharing if vaccinated. Thirty percent did not know what a vaccine was. CONCLUSIONS. These findings suggest that some in-treatment intravenous drug users would volunteer for a preventive HIV vaccine efficacy trial. Education and counseling will be required to ensure that subjects fully understand the trial's purposes, methods, risks and benefits. PMID:8179045

Ebolavirus vaccines for humans and apes.

PubMed

Fausther-Bovendo, Hugues; Mulangu, Sabue; Sullivan, Nancy J

2012-06-01

Because of high case fatality proportions, person-to-person transmission, and potential use in bioterrorism, the development of a vaccine against ebolavirus remains a top priority. Although no licensed vaccine or treatment against ebolavirus is currently available, progress in preclinical testing of countermeasures has been made. Here, we will review ebolavirus vaccine candidates and considerations for their use in humans and wild apes. Published by Elsevier B.V.

3. How comprehensive can we be in the economic assessment of vaccines?

PubMed Central

2017-01-01

ABSTRACT In two previous papers we argued on current vaccines economic assessment not fully comprehensive when using the incremental cost-utility analysis normally applied for treatments. Many differences exist between vaccines and drug treatments making vaccines economic evaluation more cumbersome. Four challenges overwhelmingly present in vaccines assessment are less important for treatments: requirements for population, societal perspectives, budget impact evaluation, and time focused objectives (control or elimination). Based on this, economic analysis of vaccines may need to be presented to many different stakeholders with various evaluation preferences, in addition to the current stakeholders involved for drugs treatment assessment. Then, we may need a tool making the inventory of the different vaccines health economic assessment programmes more comprehensive. The cauliflower value toolbox has been developed with that aim, and its use is illustrated here with rotavirus vaccine. Given the broader perspectives for vaccine assessment, it provides better value and cost evaluations. Cost-benefit analysis may be the preferred economic assessment method when considering substitution from treatment to active medical prevention. Other economic evaluation methods can be selected (i.e. optimisation modelling, return on investment) when project prioritisation is the main focus considered and when stakeholders would like to influence the development of the healthcare programme. PMID:29785253

Evaluation of the efficacy of oxytetracycline treatment followed by vaccination against Q fever in a highly infected sheep flock.

PubMed

Astobiza, Ianire; Barandika, Jesús F; Juste, Ramón A; Hurtado, Ana; García-Pérez, Ana L

2013-04-01

The aim of this research was to evaluate the efficacy of oxytetracycline treatment following an outbreak of Q fever in a sheep flock when gestation is too advanced for vaccination to be used. In such cases, immediate application of antibiotics is needed and vaccination postponed until the next breeding season. Seventy-five per cent of ewes from a dairy sheep flock affected by Q fever were treated with oxytetracycline at approximately days 100 and 120 of gestation, with the remaining 25% of the animals kept as untreated controls. Vaginal swabs, faeces and milk samples from 81 ewes (57 treated, 24 untreated) were analysed by PCR within 30 days of lambing and revealed a high percentage of Coxiella burnetii shedders. No significant differences were found between groups in either the percentage of shedders or in the mean amount of bacteria shed. In the following season 75% of the ewes and 50% of the replacement ewe lambs were vaccinated with a phase I vaccine prior to artificial insemination. Both vaccinated and control groups were homogeneously composed of ewes treated and untreated with antibiotics in the previous season. The number of shedders and the bacterial excretion load decreased significantly compared to the previous season but no statistically significant differences were found between vaccinated and control groups. In addition, no significant effect derived from the application of oxytetracycline in the previous season was observed. Vaccination was repeated for the following two seasons, and the percentage of animal shedders was reduced to minimal levels highlighting the importance of vaccination over the longer term. Copyright © 2012 Elsevier Ltd. All rights reserved.

Status of vaccine research and development of vaccines for leishmaniasis.

PubMed

Gillespie, Portia M; Beaumier, Coreen M; Strych, Ulrich; Hayward, Tara; Hotez, Peter J; Bottazzi, Maria Elena

2016-06-03

A number of leishmaniasis vaccine candidates are at various stages of pre-clinical and clinical development. Leishmaniasis is a vector-borne neglected tropical disease (NTD) caused by a protozoan parasite of the genus Leishmania and transmitted to humans by the bite of a sand fly. Visceral leishmaniasis (VL, kala-azar) is a high mortality NTD found mostly in South Asia and East Africa, while cutaneous leishmaniasis (CL) is a disfiguring NTD highly endemic in the Middle East, Central Asia, North Africa, and the Americas. Estimates attribute 50,000 annual deaths and 3.3 million disability-adjusted life years to leishmaniasis. There are only a few approved drug treatments, no prophylactic drug and no vaccine. Ideally, an effective vaccine against leishmaniasis will elicit long-lasting immunity and protect broadly against VL and CL. Vaccines such as Leish-F1, F2 and F3, developed at IDRI and designed based on selected Leishmania antigen epitopes, have been in clinical trials. Other groups, including the Sabin Vaccine Institute in collaboration with the National Institutes of Health are investigating recombinant Leishmania antigens in combination with selected sand fly salivary gland antigens in order to augment host immunity. To date, both VL and CL vaccines have been shown to be cost-effective in economic modeling studies. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Multiple Vaccinations: Friend or Foe

PubMed Central

Church, Sarah E.; Jensen, Shawn M.; Twitty, Chris; Bahjat, Keith; Hu, Hong-Ming; Urba, Walter J.; Fox, Bernard A.

2013-01-01

Few immunotherapists would accept the concept of a single vaccination inducing a therapeutic anti-cancer immune response in a patient with advanced cancer. But what is the evidence to support the “more-is-better” approach of multiple vaccinations? Since we are unaware of trials comparing the effect of a single vaccine versus multiple vaccinations on patient outcome, we considered that an anti-cancer immune response might provide a surrogate measure of the effectiveness of vaccination strategies. Since few large trials include immunological monitoring, the majority of information is gleaned from smaller trials in which an evaluation of immune responses to vaccine or tumor, before and at one or more times following the first vaccine was performed. In some studies there is convincing evidence that repeated administration of a specific vaccine can augment the immune response to antigens contained in the vaccine. In other settings multiple vaccinations can significantly reduce the immune response to one or more targets. Results from three large adjuvant vaccine studies support the potential detrimental effect of multiple vaccinations as clinical outcomes in the control arms were significantly better than that for treatment groups. Recent research has provided insights into mechanisms that are likely responsible for the reduced responses in the studies noted above, but supporting evidence from clinical specimens is generally lacking. Interpretation of these results is further complicated by the possibility that the dominant immune response may evolve to recognize epitopes not present in the vaccine. Nonetheless, the FDA-approval of the first therapeutic cancer vaccine and recent developments from preclinical models and clinical trials provide a substantial basis for optimism and a critical evaluation of cancer vaccine strategies. PMID:21952289

Structural characterization by NMR of a double phosphorylated chimeric peptide vaccine for treatment of Alzheimer's disease.

PubMed

Ramírez-Gualito, Karla; Richter, Monique; Matzapetakis, Manolis; Singer, David; Berger, Stefan

2013-04-26

Rational design of peptide vaccines becomes important for the treatment of some diseases such as Alzheimer's disease (AD) and related disorders. In this study, as part of a larger effort to explore correlations of structure and activity, we attempt to characterize the doubly phosphorylated chimeric peptide vaccine targeting a hyperphosphorylated epitope of the Tau protein. The 28-mer linear chimeric peptide consists of the double phosphorylated B cell epitope Tau₂₂₉₋₂₃₇[pThr231/pSer235] and the immunomodulatory T cell epitope Ag85B₂₄₁₋₂₅₅ originating from the well-known antigen Ag85B of the Mycobacterium tuberculosis, linked by a four amino acid sequence -GPSL-. NMR chemical shift analysis of our construct demonstrated that the synthesized peptide is essentially unfolded with a tendency to form a β-turn due to the linker. In conclusion, the -GPSL- unit presumably connects the two parts of the vaccine without transferring any structural information from one part to the other. Therefore, the double phosphorylated epitope of the Tau peptide is flexible and accessible.

The future potential for cocaine vaccines

PubMed Central

Orson, Frank M; Wang, Rongfu; Brimijoin, Stephen; Kinsey, Berma M; Singh, Rana AK; Ramakrishnan, Muthu; Wang, Helen Y; Kosten, Thomas R

2014-01-01

Introduction Addiction to cocaine is a major problem around the world, but especially in developed countries where the combination of wealth and user demand has created terrible social problems. Although only some users become truly addicted, those who are often succumb to a downward spiral in their lives from which it is very difficult to escape. From the medical perspective, the lack of effective and safe, non-addictive therapeutics has instigated efforts to develop alternative approaches for treatment, including anticocaine vaccines designed to block cocaine’s pharmacodynamic effects. Areas covered This paper discusses the implications of cocaine pharmacokinetics for robust vaccine antibody responses, the results of human vaccine clinical trials, new developments in animal models for vaccine evaluation, alternative vaccine formulations and complementary therapy to enhance anticocaine effectiveness. Expert opinion Robust anti-cocaine antibody responses are required for benefit to cocaine abusers, but since any reasonably achievable antibody level can be overcome with higher drug doses, sufficient motivation to discontinue use is also essential so that the relative barrier to cocaine effects will be appropriate for each individual. Combining a vaccine with achievable levels of an enzyme to hydrolyze cocaine to inactive metabolites, however, may substantially increase the blockade and improve treatment outcomes. PMID:24835496

[2,3-diphosphoglycerate level during the active and maintenance treatment of iron-deficiency anemia patients].

PubMed

Iordanova, E; Dosheva, I; Lulcheva, F; Tsvetkova, N; Dobrev, K

1985-01-01

The objective of the present study was to obtain information about the duration of tissue hypoxia in patients with iron deficiency anemia. That fact is of importance for the determination of the duration of maintenance iron therapy. The level of 2,3-diphosphoglycerate was studied during the treatment, after the correction of anemic syndrome and after 60-day out-patient department treatment. The data obtained revealed that the level of 2,3-diphosphoglycerate was considerably elevated, as compared with the norm, before the treatment. After the active treatment and correction of anemic syndrome it was decreased, but remaining above the norm. By the 60th day of the out-patient department treatment the decrease continued and the level of 2,3-diphosphoglycerate approached the norm.

Vaccines and bioterrorism: smallpox and anthrax.

PubMed

Kimmel, Sanford R; Mahoney, Martin C; Zimmerman, Richard K

2003-01-01

Because of the success of vaccination and the ring strategy in eradicating smallpox from the world, smallpox vaccine has not been recommended for the United States civilian populations for decades. Given the low but possible threat of bioterrorism, smallpox vaccination is now recommended for those teams investigating potential smallpox cases and for selected personnel of acute-care hospitals who would be needed to care for victims in the event of a terrorist attack. Treatment and post-exposure prophylaxis for anthrax are ciprofloxacin or doxycycline. Anthrax vaccine alone is not effective for post-exposure prevention of anthrax; vaccination is accompanied by 60 days of antibiotic therapy. In addition to military use, anthrax vaccine is recommended for pre-exposure use in those persons whose work involves repeated exposure to Bacillus anthracis spores.

Postinfluenza Vaccination Idiopathic Thrombocytopenic Purpura in Three Elderly Patients

PubMed Central

Nagasaki, Joji; Manabe, Masahiro; Ido, Kentaro; Ichihara, Hiroyoshi; Aoyama, Yasutaka; Ohta, Tadanobu; Furukawa, Yoshio; Mugitani, Atsuko

2016-01-01

The etiologies of secondary idiopathic thrombocytopenic purpura (ITP) include infection, autoimmune disease, and immunodeficiency. We report the cases of three elderly patients who developed ITP after receiving influenza vaccinations. The platelet count of an 81-year-old woman fell to 27,000/μL after she received an influenza vaccination. A 75-year-old woman developed thrombocytopenia (5,000 platelets/μL) after receiving an influenza vaccination. An 87-year-old woman whose laboratory test values included a platelet count of 2,000/μL experienced genital bleeding after receiving an influenza vaccination. After Helicobacter pylori (HP) eradication or corticosteroid treatment, all of the patients' platelet counts increased. Influenza vaccination is an underlying etiology of ITP in elderly patients. HP eradication or corticosteroid treatment is effective for these patients. Clinicians should be aware of the association between ITP and influenza vaccinations. PMID:26998369

Drying a tuberculosis vaccine without freezing.

PubMed

Wong, Yun-Ling; Sampson, Samantha; Germishuizen, Willem Andreas; Goonesekera, Sunali; Caponetti, Giovanni; Sadoff, Jerry; Bloom, Barry R; Edwards, David

2007-02-20

With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present bacillus Calmette-Guérin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model Mycobacterium (Mycobacterium smegmatis) revealed that by removing salts and cryoprotectant (e.g., glycerol) from bacterial suspensions, the significant osmotic pressures that are normally produced on bacterial membranes through droplet drying can be reduced sufficiently to minimize loss of viability on drying by up to 2 orders of magnitude. By placing the bacteria in a matrix of leucine, high-yield, free-flowing, "vial-fillable" powders of bacteria (including M. smegmatis and M. bovis BCG) can be produced. These powders show relatively minor losses of activity after maintenance at 4 degrees C and 25 degrees C up to and beyond 4 months. Comparisons with lyophilized material prepared both with the same formulation and with a commercial formulation reveal that the spray-dried BCG has better overall viability on drying.

Evaluation of intradermal vaccination at the anti rabies vaccination OPD.

PubMed

Mankeshwar, R; Silvanus, V; Akarte, S

2014-09-01

Rabies is a virtually 100% fatal acute viral encephalitis caused by an RNA virus belonging to family Rhabdoviridae and genus Lyssavirus. The virus can infect all warm blooded animals. The disease is transmitted to humans by the bite, lick or scratch of an infected animal. More than 99% of all human rabies deaths occur in the developing world. It is preventable with timely and proper usage of modern immunobiologicals (vaccines and immunoglobulins). Once exposure occurs, modern prophylaxis entails immediate wound care, local infiltration of rabies immune globulin and parenteral administration of modern cell culture vaccines in multiple doses. The annual medicinal (vaccines and other drugs) cost for animal bite treatment is Rs. 2 billion approximately (2004). The objective of the present study is to evaluate the performance of the Intradermal (i.d.) route visa vis the Intramuscular (i.m.) route in our clinical setting the Antirabies Vaccination (ARV) OPD, Sir J.J. Hospital, Mumbai. A total of 1460 patients were administered the Antirabies vaccine by the Intradermal route over the 1 year period as compared to 1075 patients who were administered the Antirabies vaccine by the Intramuscular route in the previous year. 1230 (84.2) of the patients who were administered the vaccine by the i.d. route completed the schedule and 230 (15.8%) partially completed the schedule. Four hundred thirty two (40%) of the patients who were administered the vaccine by the Intramuscular route completed the schedule and 643 (59.8%) partially completed the schedule. The vaccine cost for i.d. was Rs. 2,80,600. The vaccine cost for the intramuscular (i.m.) assuming 84% compliance was estimated as Rs. 15, 64, 000. Assuming 40% compliance the cost was estimated as Rs. 7, 82, 230. Thus a saving of Rs. 5, 01, 630 to Rs. 12, 83, 400 was effected. In our setting, the Intradermal regime was cost effective and increased patient adherence and enrolment. It has now been routinely adopted at the clinic.

New vaccines against otitis media: projected benefits and cost-effectiveness.

PubMed

O'Brien, Megan A; Prosser, Lisa A; Paradise, Jack L; Ray, G Thomas; Kulldorff, Martin; Kurs-Lasky, Marcia; Hinrichsen, Virginia L; Mehta, Jyotsna; Colborn, D Kathleen; Lieu, Tracy A

2009-06-01

New vaccines that offer protection against otitis media caused by nontypeable Haemophilus influenzae and by Moraxella catarrhalis are under development. However, the potential health benefits and economic effects of such candidate vaccines have not been systematically assessed. We created a computerized model to compare the projected benefits and costs of (1) the currently available 7-valent pneumococcal conjugate vaccine, (2) a candidate pneumococcal-nontypeable H influenzae vaccine that has been tested in Europe, (3) a hypothetical pneumococcal-nontypeable H influenzae-Moraxella vaccine, and (4) no vaccination. The clinical probabilities of acute otitis media and of otitis media with effusion were generated from multivariate analyses of data from 2 large health maintenance organizations and from the Pittsburgh Child Development/Otitis Media Study cohort. Other probabilities, costs, and quality-of-life values were derived from published and unpublished sources. The base-case analysis assumed vaccine dose costs of $65 for the 7-valent pneumococcal conjugate vaccine, $100 for the pneumococcal-nontypeable H influenzae vaccine, and $125 for the pneumococcal-nontypeable H influenzae-Moraxella vaccine. With no vaccination, we projected that 13.7 million episodes of acute otitis media would occur annually in US children aged 0 to 4 years, at an annual cost of $3.8 billion. The 7-valent pneumococcal conjugate vaccine was projected to prevent 878,000 acute otitis media episodes, or 6.4% of those that would occur with no vaccination; the corresponding value for the pneumococcal-nontypeable H influenzae vaccine was 3.7 million (27%) and for the pneumococcal-nontypeable H influenzae-Moraxella vaccine was 4.2 million (31%). Using the base-case vaccine costs, pneumococcal-nontypeable H influenzae vaccine use would result in net savings compared with nontypeable 7-valent pneumococcal conjugate use. Conversely, pneumococcal-nontypeable H influenzae-Moraxella vaccine use would not

Non-thermal plasma for inactivated-vaccine preparation.

PubMed

Wang, Guomin; Zhu, Ruihao; Yang, Licong; Wang, Kaile; Zhang, Qian; Su, Xia; Yang, Bing; Zhang, Jue; Fang, Jing

2016-02-17

Vaccines are of great importance in controlling the spread of infectious diseases in poultry farming. The safety and efficacy of vaccines are also essential. To explore the feasibility of a novel technology (non-thermal plasma) in inactivated vaccine preparation, an alternating current atmospheric pressure non-thermal plasma (NTP) jet with Ar/O2/N2 as the operating gas was used to inactivate a Newcastle disease virus (NDV, LaSota) strain and H9N2 avian influenza virus (AIV, A/Chicken/Hebei/WD/98) for vaccine preparation. The results showed that complete inactivation could be achieved with 2 min of NTP treatment for both NDV and AIV. Moreover, a proper NTP treatment time is needed for inactivation of a virus without destruction of the antigenic determinants. Compared to traditional formaldehyde-inactivated vaccine, the vaccine made from NDV treated by NTP for 2 min (NTP-2 min-NDV-vaccine) could induce a higher NDV-specific antibody titer in specific pathogen-free (SPF) chickens, and the results of a chicken challenge experiment showed that NTP-2 min-NDV-vaccine could protect SPF chickens from a lethal NDV challenge. Vaccines made from AIV treated by NTP for 2 min (NTP-2 min-AIV-vaccine) also showed a similar AIV-specific antibody titer compared with traditional AIV vaccines prepared using formaldehyde inactivation. Studies of the morphological changes of the virus, chemical analysis of NDV allantoic fluid and optical emission spectrum analysis of NTP suggested that reactive oxygen species and reactive nitrogen species produced by NTP played an important role in the virus inactivation process. All of these results demonstrated that it could be feasible to use non-thermal NTP as an alternative strategy to prepare inactivated vaccines for Newcastle disease and avian influenza. Copyright © 2015 Elsevier Ltd. All rights reserved.

Activity of glycated chitosan and other adjuvants to PDT vaccines

NASA Astrophysics Data System (ADS)

Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

2015-03-01

Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

Lead particle size and its association with firing conditions and range maintenance: implications for treatment.

PubMed

Dermatas, Dimitris; Chrysochoou, Maria

2007-08-01

Six firing range soils were analyzed, representing different environments, firing conditions, and maintenance practices. The particle size distribution and lead (Pb) concentration in each soil fraction were determined for samples obtained from the backstop berms. The main factors that were found to influence Pb fragment size were the type of soil used to construct the berms and the type of weapon fired. The firing of high velocity weapons, i.e., rifles, onto highly angular soils induced significant fragmentation of the bullets and/or pulverization of the soil itself. This resulted in the accumulation of Pb in the finer soil fractions and the spread of Pb contamination beyond the vicinity of the backstop berm. Conversely, the use of clay as backstop and the use of low velocity pistols proved to be favorable for soil clean-up and range maintenance, since Pb was mainly present as large metallic fragments that can be recovered by a simple screening process. Other factors that played important roles in Pb particle size distribution were soil chemistry, firing distance, and maintenance practices, such as the use of water spray for dust suppression and deflectors prior to impact. Overall, coarse Pb particles provide much easier and more cost-effective maintenance, soil clean-up, and remediation via physical separation. Fine Pb particles release Pb more easily, pose an airborne Pb hazard, and require the application of stabilization/solidification treatment methods. Thus, to ensure sustainable firing range operations by means of cost-effective design, maintenance, and clean-up, especially when high velocity weapons are used, the above mentioned factors should be carefully considered.

Seasonal influenza vaccination rates and reasons for non-vaccination in children with gastrointestinal disorders.

PubMed

Peleg, Noam; Zevit, Noam; Shamir, Raanan; Chodick, Gabriel; Levy, Itzhak

2015-01-01

Despite advances in the treatment and prevention of influenza, it is still considered an important cause of morbidity and mortality worldwide. Annual vaccination is the safest and most effective mean of prevention. Our study aims were to explore the uptake of influenza vaccination among children with gastrointestinal disorders, and to characterize non-adherent patients. The present cross-sectional study included parents of pediatric patients attending the Gastroenterology Institute at Schneider Children's Medical Center of Israel between September and October 2011. Parents were asked to complete a questionnaire concerning demographic and clinical parameters, influenza vaccination of the child, and reasons for not vaccinating the child, when appropriate. The study population included 273 patients (50% female), with a median age of 10 years (range, 2-18 years). Overall, the rate of seasonal influenza vaccination was 30.8%. Higher rates were found among immunosuppressed patients (46.1%), and in patients with inflammatory bowel disease (50%). There was no significant effect of patient age, gender, ethnic origin or parental level of education on the vaccination rate. Vaccination rates were significantly associated with parents' information and knowledge of, as well as their personal beliefs regarding the vaccine (P<0.001). Influenza vaccination rates are relatively low in the pediatric population attending gastroenterology clinics, in both high- and low-risk groups. The importance of parental knowledge in compliance with influenza vaccination of children should prompt general pediatricians and gastroenterologists to discuss and address the common misconceptions regarding the vaccine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with smallpox vaccine does not compromise vaccine protection in mice challenged with ectromelia virus.

PubMed

Parker, Scott; Crump, Ryan; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Lanier, E Randall; Painter, George; Schriewer, Jill; Trost, Lawrence C; Buller, R Mark

2014-11-01

Natural orthopoxvirus outbreaks such as vaccinia, cowpox, cattlepox and buffalopox continue to cause morbidity in the human population. Monkeypox virus remains a significant agent of morbidity and mortality in Africa. Furthermore, monkeypox virus's broad host-range and expanding environs make it of particular concern as an emerging human pathogen. Monkeypox virus and variola virus (the etiological agent of smallpox) are both potential agents of bioterrorism. The first line response to orthopoxvirus disease is through vaccination with first-generation and second-generation vaccines, such as Dryvax and ACAM2000. Although these vaccines provide excellent protection, their widespread use is impeded by the high level of adverse events associated with vaccination using live, attenuated virus. It is possible that vaccines could be used in combination with antiviral drugs to reduce the incidence and severity of vaccine-associated adverse events, or as a preventive in individuals with uncertain exposure status or contraindication to vaccination. We have used the intranasal mousepox (ectromelia) model to evaluate the efficacy of vaccination with Dryvax or ACAM2000 in conjunction with treatment using the broad spectrum antiviral, brincidofovir (BCV, CMX001). We found that co-treatment with BCV reduced the severity of vaccination-associated lesion development. Although the immune response to vaccination was quantifiably attenuated, vaccination combined with BCV treatment did not alter the development of full protective immunity, even when administered two days following ectromelia challenge. Studies with a non-replicating vaccine, ACAM3000 (MVA), confirmed that BCV's mechanism of attenuating the immune response following vaccination with live virus was, as expected, by limiting viral replication and not through inhibition of the immune system. These studies suggest that, in the setting of post-exposure prophylaxis, co-administration of BCV with vaccination should be considered

Economic value of dengue vaccine in Thailand.

PubMed

Lee, Bruce Y; Connor, Diana L; Kitchen, Sarah B; Bacon, Kristina M; Shah, Mirat; Brown, Shawn T; Bailey, Rachel R; Laosiritaworn, Yongjua; Burke, Donald S; Cummings, Derek A T

2011-05-01

With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [< 1× per capita gross domestic product (GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [< 3× per capita GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving.

Economic Value of Dengue Vaccine in Thailand

PubMed Central

Lee, Bruce Y.; Connor, Diana L.; Kitchen, Sarah B.; Bacon, Kristina M.; Shah, Mirat; Brown, Shawn T.; Bailey, Rachel R.; Laosiritaworn, Yongjua; Burke, Donald S.; Cummings, Derek A. T.

2011-01-01

With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [< 1× per capita gross domestic product (GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [< 3× per capita GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving. PMID:21540387

Vaccines against biologic agents: uses and developments.

PubMed

Ales, Noel C; Katial, Rohit K

2004-03-01

Although the Geneva protocol that prohibits the use of chemical and biologic weapons was ratified in 1925, many countries failed to accept this protocol: others stipulated retaliation, and some, like the United States, did not ratify the protocol for decades. This delay allowed the continued development of chemical and biologic agents. Members of the health care community are responsible for determining the best way to protect society from the potentially devastating effects of these biologic agents. Ideally,these diseases would be prevented from ever developing into systemic illnesses. In the past, vaccination has been a successful means of eradicating disease. Vaccines remain a hopeful therapy for the future, but time is short,and there are many obstacles.Information regarding bioterrorism agents and their treatments comes mainly from dated data or from in vitro or animal studies that may not apply to human treatment and disease. Additionally, the current threat of bioterrorism does not allow enough time for accurate, well-designed,controlled studies in humans before the release of investigational vaccines. Furthermore, some human studies would not be safe or ethical. Finally,many members of society suffer from illnesses that would put them at high risk to receive prophylactic vaccination. It is therefore naive to believe that vaccines would be the ultimate protection from these agents. In addition to vaccine development, there must be concurrent investigations into disease management and treatment. Even in instances in which vaccination is known to be an effective means of disease protection. biologic agents may be presented in a manner that renders vaccines ineffective. Virulent strains of organisms may be used, more than one organism may be used in tandem to increase virulence, and strains may be selected for antibiotic and vaccine resistance. Genetically engineered strains may use virulence factors other than those targeted in vaccines, and high

Oral Aripiprazole as Maintenance Treatment in Adolescent Schizophrenia: Results From a 52-Week, Randomized, Placebo-Controlled Withdrawal Study.

PubMed

Correll, Christoph U; Kohegyi, Eva; Zhao, Cathy; Baker, Ross A; McQuade, Robert; Salzman, Phyllis M; Sanchez, Raymond; Nyilas, Margaretta; Carson, William

2017-09-01

To evaluate the efficacy, safety, and tolerability of aripiprazole, a dopamine D 2 receptor partial agonist, as maintenance treatment in adolescent outpatients with schizophrenia. This was a multicenter, double-blind, placebo-controlled, randomized withdrawal design trial. Participants 13 to 17 years of age with a diagnosis of schizophrenia (DSM-IV-TR) were first cross-titrated from their other oral antipsychotic(s) (4-6 weeks), then stabilized (7-21 weeks) on oral aripiprazole 10 to 30 mg/d, and finally randomized 2:1 to continuation of oral aripiprazole or to placebo in a double-blind maintenance phase (≤52 weeks). The primary endpoint was time from randomization to exacerbation of psychotic symptoms/impending relapse. Safety and tolerability were assessed. Of 201 enrolled participants, 146 were randomized to aripiprazole (n = 98) or placebo (n = 48) in the double-blind maintenance phase. Treatment with aripiprazole was associated with a significantly longer time to exacerbation of psychotic symptoms/impending relapse compared with placebo (hazard ratio, 0.46 [95% CI = 0.24-0.88]; p = .016). Aripiprazole was associated with lower rates of serious treatment-emergent adverse events (TEAEs) versus placebo (3.1% versus 12.5%; p = .059) and severe TEAEs (2.0% versus 10.4%; p = .039). The rate of discontinuation due to TEAEs was lower with aripiprazole versus placebo (20.4% versus 39.6%, p = .014; number-needed-to-harm = 5.1). The incidences of extrapyramidal symptoms, weight gain, and somnolence were similar or lower with aripiprazole than with placebo, and no TEAEs related to elevated serum prolactin were reported. Based on Tanner staging, 27.6% of participants treated with aripiprazole and 16.7% of those who received placebo progressed one or two stages from baseline. Aripiprazole was observed to be safe and effective for the maintenance treatment of adolescents with schizophrenia. Efficacy and Safety Study of Oral Aripiprazole in Adolescents With

Best practices and performance assessment for preventive maintenance treatments for Virginia pavements.

DOT National Transportation Integrated Search

2015-08-01

Preventive maintenance has the potential to improve network condition by retarding future pavement deterioration. This : report outlines guidelines for implementing a preventive maintenance policy for bituminous pavements. : Preventive maintenance tr...

A freeze-stable formulation for DTwP and DTaP vaccines.

PubMed

Xue, Honggang; Yang, Bangling; Kristensen, Debra D; Chen, Dexiang

2014-01-01

Inadvertent vaccine freezing often occurs in the cold chain and may cause damage to freeze‑sensitive vaccines. Liquid vaccines that contain aluminum salt adjuvants are particularly vulnerable. Polyol cryoprotective excipients have been shown to prevent freeze damage to hepatitis B vaccine. In this study, we examined the freeze-protective effect of propylene glycol on diphtheria-tetanus-pertussis-whole-cell (DTwP) and acellular (DTaP) vaccines. Pilot lots of DTwP and DTaP formulated with 7.5% propylene glycol underwent 3 freeze-thaw treatments. The addition of propylene glycol had no impact on pH, particle size distribution, or potency of the vaccines prior to freeze-thaw treatment; the only change noted was an increase in osmolality. The potencies and the physical properties of the vaccines containing cryoprotectant were maintained after freeze-thawing and for 3 months in accelerated stability studies. The results from this study indicate that formulating vaccines with propylene glycol can protect diphtheria-tetanus-pertussis vaccines against freeze damages.

On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprine or 6-mercaptopurine intolerant IBD patients

PubMed Central

de Boer, Nanne KH; Derijks, Luc JJ; Gilissen, Lennard PL; Hommes, Daniel W; Engels, Leopold GJB; de Boer, Sybrand Y; den Hartog, Gijsbertus; Hooymans, Piet M; Mäkelburg, Anja BU; Westerveld, Barend D; Naber, Anton HJ; Mulder, Chris JJ; de Jong, Dirk J

2005-01-01

AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year. METHODS: Database analysis. RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%) and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly. CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials. PMID:16222751

Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy.

PubMed

Palou-Redorta, J; Solsona, E; Angulo, J; Fernández, J M; Madero, R; Unda, M; Martínez-Piñeiro, J A; Portillo, J; Chantada, V; Moyano, J L

2016-01-01

To compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumours; however, a number of experts still question the need for maintenance BCG. We retrospectively analysed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumour (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n=108), re-TURBT (n=153), induction with 27mg of BCG (Connaught strain) (n=87), induction with 81mg of BCG (n=489) or induction with 81mg of BCG+maintenance (n=202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan-Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. The mean follow-up was 62±39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81mg of BCG than in the other treatment groups (P<.001). The risk of tumour progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27mg of BCG (P=.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; P=.003). In the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Inactivated poliovirus vaccine and the final stages of poliovirus eradication.

PubMed

Hovi, T

2001-03-21

The use of the inactivated poliovirus vaccine (IPV) will increase before and probably also after the global eradication of the wild type poliovirus. Before eradication, the switch from the use of oral poliovirus vaccine (OPV) to IPV has been due to the better safety record of IPV. Introduction of IPV in the regular immunisation schedules is made easier by the development of several combination vaccines, including IPV. Maternal antibodies and young age, often considered problematic for early initiation of IPV schedules, did not compromise optimal maintenance of seropositivity during infancy or long-term persisting antibody levels in our studies. OPV-derived, potentially pathogenic and transmissible poliovirus strains, excreted by some individuals for years, may present a problem for a blunt stopping of all polio immunisations after eradication. Our recent results suggest that locally excreted IgA might have a role in the elimination of poliovirus infection in the intestinal tissues.

Production and dose determination of the Infection and Treatment Method (ITM) Muguga cocktail vaccine used to control East Coast fever in cattle.

PubMed

Patel, Ekta; Mwaura, Stephen; Kiara, Henry; Morzaria, Subhash; Peters, Andrew; Toye, Philip

2016-03-01

The Infection and Treatment Method (ITM) of vaccination against the apicomplexan parasite Theileria parva has been used since the early 1970s and is still the only commercially available vaccine to combat the fatal bovine disease, East Coast fever (ECF). The disease is tick-transmitted and results in annual economic losses of at least $300 million per year. While this vaccine technology has been available for over 40 years, few attempts have been made to standardize the production process and characterize the vaccine. The latest batch was produced in early 2008 at the International Livestock Research Institute (ILRI). The vaccine production involves the use of cattle free from parasites routinely monitored throughout the production process, and a pathogen-free tick colony. This paper describes the protocol used in the recent production, and the process improvements, including improved quality control tools, that had not been employed in previous ITM productions. The paper also describes the processes involved in determining the appropriate field dose, which involved a three-step in vivo study with various dilutions of the vaccine stabilate. The vaccine was shown to be safe and viable after production, and a suitable field dose was identified as 1 ml of a 1:100 dilution. Copyright © 2015 Elsevier GmbH. All rights reserved.

Medical Management of Acute Radiation Syndromes : Immunoprophylaxis by Antiradiation Vaccine

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael; Kedar, Prasad

Introduction: Traditionally, the treatment of Acute Radiation Syndrome (ARS) includes supportive therapy, cytokine therapy, blood component transfusions and even stem cell transplantation. Recommendations for ARS treatment are based on clinical symptoms, laboratory results, radiation exposure doses and information received from medical examinations. However, the current medical management of ARS does not include immune prophylaxis based on antiradiation vaccines or immune therapy with hyperimmune antiradiation serum. Immuneprophylaxis of ARS could result from stimulating the immune system via immunization with small doses of radiation toxins (Specific Radiation Determinants-SRD) that possess significant immuno-stimulatory properties. Methods: Principles of immuno-toxicology were used to derive this method of immune prophylaxis. An antiradiation vaccine containing a mixture of Hematotoxic, Neurotoxic and Non-bacterial (GI) radiation toxins, underwent modification into a toxoid forms of the original SRD radiation toxins. The vaccine was administered to animals at different times prior to irradiation. The animals were subjected to lethal doses of radiation that induced different forms of ARS at LD 100/30. Survival rates and clinical symptoms were observed in both control and vaccine-treated animals. Results: Vaccination with non-toxic doses of Radiation toxoids induced immunity from the elaborated Specific Radiation Determinant (SRD) toxins. Neutralization of radiation toxins by specific antiradiation antibodies resulted in significantly improved clinical symptoms in the severe forms of ARS and observed survival rates of 60-80% in animals subjected to lethal doses of radiation expected to induce different forms of ARS at LD 100/30. The most effective vaccination schedule for the antiradiation vaccine consisted of repeated injections 24 and 34 days before irradiation. The vaccine remained effective for the next two years, although the specific immune memory probably

Vaccines for preventing anthrax.

PubMed

Donegan, Sarah; Bellamy, Richard; Gamble, Carrol L

2009-04-15

Anthrax is a bacterial zoonosis that occasionally causes human disease and is potentially fatal. Anthrax vaccines include a live-attenuated vaccine, an alum-precipitated cell-free filtrate vaccine, and a recombinant protein vaccine. To evaluate the effectiveness, immunogenicity, and safety of vaccines for preventing anthrax. We searched the following databases (November 2008): Cochrane Infectious Diseases Group Specialized Register; CENTRAL (The Cochrane Library 2008, Issue 4); MEDLINE; EMBASE; LILACS; and mRCT. We also searched reference lists. We included randomized controlled trials (RCTs) of individuals and cluster-RCTs comparing anthrax vaccine with placebo, other (non-anthrax) vaccines, or no intervention; or comparing administration routes or treatment regimens of anthrax vaccine. Two authors independently considered trial eligibility, assessed risk of bias, and extracted data. We presented cases of anthrax and seroconversion rates using risk ratios (RR) and 95% confidence intervals (CI). We summarized immunoglobulin G (IgG) concentrations using geometric means. We carried out a sensitivity analysis to investigate the effect of clustering on the results from one cluster-RCT. No meta-analysis was undertaken. One cluster-RCT (with 157,259 participants) and four RCTs of individuals (1917 participants) met the inclusion criteria. The cluster-RCT from the former USSR showed that, compared with no vaccine, a live-attenuated vaccine (called STI) protected against clinical anthrax whether given by a needleless device (RR 0.16; 102,737 participants, 154 clusters) or the scarification method (RR 0.25; 104,496 participants, 151 clusters). Confidence intervals were statistically significant in unadjusted calculations, but when a small amount of association within clusters was assumed, the differences were not statistically significant. The four RCTs (of individuals) of inactivated vaccines (anthrax vaccine absorbed and recombinant protective antigen) showed a dose

Burrow Dusting or Oral Vaccination Prevents Plague-Associated Prairie Dog Colony Collapse.

PubMed

Tripp, Daniel W; Rocke, Tonie E; Runge, Jonathan P; Abbott, Rachel C; Miller, Michael W

2017-09-01

Plague impacts prairie dogs (Cynomys spp.), the endangered black-footed ferret (Mustela nigripes) and other sensitive wildlife species. We compared efficacy of prophylactic treatments (burrow dusting with deltamethrin or oral vaccination with recombinant "sylvatic plague vaccine" [RCN-F1/V307]) to placebo treatment in black-tailed prairie dog (C. ludovicianus) colonies. Between 2013 and 2015, we measured prairie dog apparent survival, burrow activity and flea abundance on triplicate plots ("blocks") receiving dust, vaccine or placebo treatment. Epizootic plague affected all three blocks but emerged asynchronously. Dust plots had fewer fleas per burrow (P < 0.0001), and prairie dogs captured on dust plots had fewer fleas (P < 0.0001) than those on vaccine or placebo plots. Burrow activity and prairie dog density declined sharply in placebo plots when epizootic plague emerged. Patterns in corresponding dust and vaccine plots were less consistent and appeared strongly influenced by timing of treatment applications relative to plague emergence. Deltamethrin or oral vaccination enhanced apparent survival within two blocks. Applying insecticide or vaccine prior to epizootic emergence blunted effects of plague on prairie dog survival and abundance, thereby preventing colony collapse. Successful plague mitigation will likely entail strategic combined uses of burrow dusting and oral vaccination within large colonies or colony complexes.

Vaccines for the common cold.

PubMed

Simancas-Racines, Daniel; Guerra, Claudia V; Hidalgo, Ricardo

2013-06-12

vaccines for preventing the common cold in healthy people. We identified the need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Unless RCTs provide evidence of a treatment effect and the trade-off between potential benefits and harms is established, policy-makers, clinicians and academics should not recommend the use of vaccines for preventing the common cold in healthy people. Any future trials on medical treatments for preventing the common cold should assess a variety of virus vaccines for this condition. Outcome measures should include common cold incidence, vaccine safety and mortality related to the vaccine.

Leaky vaccines protect highly exposed recipients at a lower rate: implications for vaccine efficacy estimation and sieve analysis.

PubMed

Edlefsen, Paul T

2014-01-01

"Leaky" vaccines are those for which vaccine-induced protection reduces infection rates on a per-exposure basis, as opposed to "all-or-none" vaccines, which reduce infection rates to zero for some fraction of subjects, independent of the number of exposures. Leaky vaccines therefore protect subjects with fewer exposures at a higher effective rate than subjects with more exposures. This simple observation has serious implications for analysis methodologies that rely on the assumption that the vaccine effect is homogeneous across subjects. We argue and show through examples that this heterogeneous vaccine effect leads to a violation of the proportional hazards assumption, to incomparability of infected cases across treatment groups, and to nonindependence of the distributions of the competing failure processes in a competing risks setting. We discuss implications for vaccine efficacy estimation, correlates of protection analysis, and mark-specific efficacy analysis (also known as sieve analysis).

Opportunities and strategies to further reduce animal use for Leptospira vaccine potency testing.

PubMed

Walker, A; Srinivas, G B

2013-09-01

Hamsters are routinely infected with virulent Leptospira for two purposes in the regulation of biologics: the performance of Codified potency tests and maintenance of challenge culture for the Codified potency tests. Options for reducing animal use in these processes were explored in a plenary lecture at the "International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing: State of the Science and the Way Forward" held at the Center for Veterinary Biologics in September 2012. The use of validated in vitro potency assays such as those developed by the U.S. Department of Agriculture for Leptospira (L.) canicola, Leptospira grippotyphosa, Leptospira pomona, and Leptospira icterohaemorrhagiae rather than the Codified hamster vaccination-challenge assay was encouraged. Alternatives such as reduced animal numbers in the hamster vaccination-challenge testing were considered for problematic situations. Specifically, the merits of sharing challenge controls, reducing group sizes, and eliminating animals for concurrent challenge dose titration were assessed. Options for maintaining virulent, stable cultures without serial passage through hamsters or with decreased hamster use were also discussed. The maintenance of virulent Leptospira without the use of live animals is especially difficult since a reliable means to maintain virulence after multiple in vitro passages has not yet been identified. Published by Elsevier Ltd.

Tuberculosis vaccine development at a divide.

PubMed

Kaufmann, Stefan H E

2014-05-01

Tuberculosis (TB) remains a major health threat that will only be defeated by a combination of better drugs, diagnostics and vaccines. The only licensed TB vaccine, bacille Calmette-Guérin (BCG), protects against extrapulmonary TB in infants. Novel vaccine candidates that could protect against pulmonary TB either in TB naïve or in latent TB-infected healthy individuals have been developed and are currently being assessed in clinical trials. Subunit booster vaccines are either based on viral vectors expressing TB-specific antigens or on TB-protein antigens in adjuvants. Subunit vaccines are administered on top of BCG. Replacement vaccines for BCG are recombinant viable BCG or Mycobacterium tuberculosis. Several candidates are undergoing, or will soon start, phase IIb assessment for efficacy. The first vaccine candidate, MVA85A, to complete a phase IIb trial, unfortunately failed to show protection against TB in infants. Therapeutic vaccines composed of killed mycobacterial preparations target patients with complicated TB in adjunct to drug treatment. With increasing numbers of TB vaccine candidates in clinical trials, financial, regulatory and infrastructural issues arise, which would be best tackled by a global strategy. In addition, selection of the most promising vaccine candidates for further clinical development gains increasing importance.

TLR3 and TLR9 agonists improve postexposure vaccination efficacy of live smallpox vaccines.

PubMed

Israely, Tomer; Melamed, Sharon; Achdout, Hagit; Erez, Noam; Politi, Boaz; Waner, Trevor; Lustig, Shlomo; Paran, Nir

2014-01-01

Eradication of smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release. Intranasal infection of mice with ectromelia virus (ECTV), a model for human smallpox, is curable by vaccination with a high vaccine dose given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mice were vaccinated postexposure with Vaccinia-Lister, the conventional smallpox vaccine or Modified Vaccinia Ankara, a highly attenuated vaccine in conjunction with TLR3 or TLR9 agonists. We show that co-administration of the TLR3 agonist poly(I:C) even 5 days postexposure conferred protection, avoiding the need to increase the vaccination dose. Efficacious treatments prevented death, ameliorated disease symptoms, reduced viral load and maintained tissue integrity of target organs. Protection was associated with significant elevation of serum IFNα and anti-vaccinia IgM antibodies, modulation of IFNγ response, and balanced activation of NK and T cells. TLR9 agonists (CpG ODNs) were less protective than the TLR3 agonist poly(I:C). We show that activation of type 1 IFN by poly(I:C) and protection is achievable even without co-vaccination, requiring sufficient amount of the viral antigens of the infective agent or the vaccine. This study demonstrated the therapeutic potential of postexposure immune modulation by TLR activation, allowing to alleviate the disease symptoms and to further extend the protective window of postexposure vaccination.

TLR3 and TLR9 Agonists Improve Postexposure Vaccination Efficacy of Live Smallpox Vaccines

PubMed Central

Israely, Tomer; Erez, Noam; Politi, Boaz; Waner, Trevor; Lustig, Shlomo; Paran, Nir

2014-01-01

Eradication of smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release. Intranasal infection of mice with ectromelia virus (ECTV), a model for human smallpox, is curable by vaccination with a high vaccine dose given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mice were vaccinated postexposure with Vaccinia-Lister, the conventional smallpox vaccine or Modified Vaccinia Ankara, a highly attenuated vaccine in conjunction with TLR3 or TLR9 agonists. We show that co-administration of the TLR3 agonist poly(I:C) even 5 days postexposure conferred protection, avoiding the need to increase the vaccination dose. Efficacious treatments prevented death, ameliorated disease symptoms, reduced viral load and maintained tissue integrity of target organs. Protection was associated with significant elevation of serum IFNα and anti-vaccinia IgM antibodies, modulation of IFNγ response, and balanced activation of NK and T cells. TLR9 agonists (CpG ODNs) were less protective than the TLR3 agonist poly(I:C). We show that activation of type 1 IFN by poly(I:C) and protection is achievable even without co-vaccination, requiring sufficient amount of the viral antigens of the infective agent or the vaccine. This study demonstrated the therapeutic potential of postexposure immune modulation by TLR activation, allowing to alleviate the disease symptoms and to further extend the protective window of postexposure vaccination. PMID:25350003

Optimal vaccination and bednet maintenance for the control of malaria in a region with naturally acquired immunity.

PubMed

Prosper, Olivia; Ruktanonchai, Nick; Martcheva, Maia

2014-07-21

Following over two decades of research, the malaria vaccine candidate RTS,S has reached the final stages of vaccine trials, demonstrating an efficacy of roughly 50% in young children. Regions with high malaria prevalence tend to have high levels of naturally acquired immunity (NAI) to severe malaria; NAI is caused by repeated exposure to infectious bites and results in large asymptomatic populations. To address concerns about how these vaccines will perform in regions with existing NAI, we developed a simple malaria model incorporating vaccination and NAI. Typically, if the basic reproduction number (R0) for malaria is greater than unity, the disease will persist; otherwise, the disease will become extinct. However, analysis of this model revealed that NAI, compounded by a subpopulation with only partial protection to malaria, may render vaccination efforts ineffective and potentially detrimental to malaria control, by increasing R0 and increasing the likelihood of malaria persistence even when R0<1. The likelihood of this scenario increases when non-immune infected individuals are treated disproportionately compared with partially immune individuals - a plausible scenario since partially immune individuals are more likely to be asymptomatically infected. Consequently, we argue that active case-detection of asymptomatic infections is a critical component of an effective malaria control program. We then investigated optimal vaccination and bednet control programs under two endemic settings with varying levels of naturally acquired immunity: a typical setting under which prevalence decays when R0<1, and a setting in which subthreshold endemic equilibria exist. A qualitative comparison of the optimal control results under the first setting revealed that the optimal policy differs depending on whether the goal is to reduce total morbidity, or to reduce clinical infections. Furthermore, this comparison dictates that control programs should place less effort in

Ebola vaccine, therapeutics, and diagnostics.

PubMed

Furuyama, Wakako; Takada, Ayato

2016-01-01

Ebolaviruses, members of the family Filoviridae, cause severe hemorrhagic fever in humans and nonhuman primates, with human case fatality rates of up to 90%. No effective prophylaxis or treatment for Ebola virus disease (EVD) is yet commercially available. During the latest outbreak of EVD in West Africa, several unapproved drugs were used for the treatment of patients. This outbreak has indeed accelerated efforts to develop antiviral strategies and some of the vaccine and drug candidates have undergone clinical trials. This article reviews previous researches and recent advances on the development of vaccine, therapeutics, and diagnostics for EVD.

Patterns of pre-treatment drug abuse, drug treatment history and characteristics of addicts in methadone maintenance treatment in Iran

PubMed Central

2012-01-01

Background Opiates are the main drugs of abuse, and Methadone Maintenance Treatment (MMT) is the most widely administered drug addiction treatment program in Iran. Our study aimed to investigate patterns of pre-treatment drug abuse, addiction treatment history and characteristics of patients in MMT in Tehran. Methods We applied a stratified cluster random sampling technique and conducted a cross-sectional survey utilizing a standard patient characteristic and addiction history form with patients (n = 810) in MMT. The Chi-square test and t-test served for statistical analyses. Results A clear majority of the participants were men (96%), more than 60% of whom were between 25 and 44 years of age, educated (89% had more than elementary education), and employed (>70%). The most commonly reported main drugs of abuse prior to MMT entry were opium (69%) and crystalline heroin (24%). The patients’ lifetime drug experience included opium (92%), crystalline heroin (28%), cannabis (16%), amphetamines (15%), and other drugs (33%). Crystalline heroin abusers were younger than opium users, had begun abusing drugs earlier, and reported a shorter history of opiate addiction. Conclusion Opium and crystalline heroin were the main drugs of abuse. A high rate of addiction using more dangerous opiate drugs such as crystalline heroin calls for more preventive efforts, especially among young men. PMID:22676557

Treatment readiness, attitudes toward, and experiences with methadone and buprenorphine maintenance therapy among people who inject drugs in Malaysia.

PubMed

Vijay, Aishwarya; Bazazi, Alexander R; Yee, Ilias; Kamarulzaman, Adeeba; Altice, Frederick L

2015-07-01

Little is known about attitudes toward and experiences with opioid maintenance therapy (OMT) among people who inject drugs in Malaysia, a country where people who inject drugs comprise 1.3% of the adult population. In 2010, 460 people who inject drugs in Greater Kuala Lumpur, Malaysia were surveyed to evaluate attitudes toward and experiences with OMT and treatment readiness. Attitudes towards OMT with both methadone and buprenorphine were assessed using an opinions scale. Multivariable linear regression was used to assess correlates of treatment readiness, measured with the 19-item Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). All 460 participants used opioids and nearly all (99.1%) met criteria for opioid dependence. Few had had previous experience with methadone (9.3%) or buprenorphine (12.6%) maintenance therapy, yet many had used methadone (55.2%) or buprenorphine (51.7%) outside of treatment settings. Fifteen percent had injected buprenorphine in the past month, and of the few that were currently receiving buprenorphine maintenance therapy, almost all were injecting it. The majority of subjects exhibited a moderate level of treatment readiness and a preference for methadone over buprenorphine. Those with low treatment readiness scores were more likely to have previous experience with compulsory drug detention centers (p<0.01), needle/syringe exchange programs (p<0.005), or be of Indian ethnicity (p<0.001). Past use of methadone (p<0.01), older age (p<0.001), higher stress symptom severity (p<0.001), and sharing of needles or syringes (p<0.05) were associated with higher treatment readiness scores. There are suboptimal levels of OMT experience among people who inject drugs that may be improved by addressing factors that influence patient attitudes. Those individuals with moderate treatment readiness may be targeted by brief motivational and cognitive interventions in primary care, prisons or OMT clinics aimed at improving entry into and

Treatment readiness, attitudes toward, and experiences with methadone and buprenorphine maintenance therapy among people who inject drugs in Malaysia

PubMed Central

Vijay, Aishwarya; Bazazi, Alexander R.; Yee, Ilias; Kamarulzaman, Adeeba; Altice, Frederick L.

2016-01-01

Background Little is known about attitudes toward and experiences with opioid maintenance therapy (OMT) among people who inject drugs in Malaysia, a country where people who inject drugs comprise 1.3% of the adult population. Methods In 2010, 460 people who inject drugs in Greater Kuala Lumpur, Malaysia were surveyed to evaluate attitudes toward and experience with OMT and treatment readiness. Attitudes towards OMT with both methadone and buprenorphine were assessed using an opinions scale. Multivariable linear regression was used to assess correlates of treatment readiness, measured with the 19-item Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). Results All 460 participants used opioids and nearly all (99.1%) met criteria for opioid dependence. Few had had previous experience with methadone (9.3%) or buprenorphine (12.6%) maintenance therapy, yet many had used methadone (55.2%) or buprenorphine (51.7%) outside of treatment settings. Fifteen percent had injected buprenorphine in the past month, and of the few that were currently receiving buprenorphine maintenance therapy, almost all were injecting it. The majority of subjects exhibited a moderate level of treatment readiness and a preference for methadone over buprenorphine. Those with low treatment readiness scores were more likely to have previous experience with compulsory drug detention centers (p<0.01), needle/syringe exchange programs (p<0.005), or be of Indian ethnicity (p<0.001). Past use of methadone (p<0.01), older age (p<0.001), stress symptom severity (p<0.001), and sharing of needles or syringes (p<0.05) were associated with higher treatment readiness scores. Conclusion There are suboptimal levels of OMT experience among people who inject drugs that may be improved by addressing factors that influence patient attitudes. Those individuals with moderate treatment readiness may be targeted by brief motivational and cognitive interventions in primary care, prisons or OMT clinics

Baclofen for maintenance treatment of opioid dependence: A randomized double-blind placebo-controlled clinical trial [ISRCTN32121581

PubMed Central

Assadi, Seyed Mohammad; Radgoodarzi, Reza; Ahmadi-Abhari, Seyed Ali

2003-01-01

Background Results of preclinical studies suggest that the GABAB receptor agonist baclofen may be useful in treatment of opioid dependence. This study was aimed at assessing the possible efficacy of baclofen for maintenance treatment of opioid dependence. Methods A total of 40 opioid-dependent patients were detoxified and randomly assigned to receive baclofen (60 mg/day) or placebo in a 12-week, double blind, parallel-group trial. Primary outcome measure was retention in treatment. Secondary outcome measures included opioids and alcohol use according to urinalysis and self-report ratings, intensity of opioid craving assessed with a visual analogue scale, opioid withdrawal symptoms as measured by the Short Opiate Withdrawal Scale and depression scores on the Hamilton inventory. Results Treatment retention was significantly higher in the baclofen group. Baclofen also showed a significant superiority over placebo in terms of opiate withdrawal syndrome and depressive symptoms. Non-significant, but generally favorable responses were seen in the baclofen group with other outcome measures including intensity of opioid craving and self-reported opioid and alcohol use. However, no significant difference was seen in the rates of opioid-positive urine tests. Additionally, the drug side effects of the two groups were not significantly different. Conclusion The results support further study of baclofen in the maintenance treatment of opioid dependence. PMID:14624703

Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum Study (TEOSS)

PubMed Central

Findling, Robert L; Johnson, Jacqueline L; McClellan, Jon; Frazier, Jean A; Vitiello, Benedetto; Hamer, Robert M; Lieberman, Jeffrey A; Ritz, Louise; McNamara, Nora K; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

2010-01-01

OBJECTIVE To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders (EOSS). METHOD Patients (age 8–19 years) who had improved during an 8-week, randomized double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed following defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. RESULTS Of the 116 youth randomized in the acute trial, 54 entered maintenance treatment (molindone, N=20; olanzapine, N=13; risperidone, N=21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (N=15), inadequate efficacy (N=14), or study non-adherence (N=8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom reduction or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. CONCLUSIONS Only 12 % of youth with EOSS continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for EOSS. PMID:20494268

Variation in the Viral Hepatitis and HIV Policies and Practices of Methadone Maintenance Programs.

PubMed

Jessop, Amy B; Hom, Jeffrey K; Burke, Monika

Patients prescribed methadone maintenance treatment (MMT) demonstrate elevated prevalence of hepatitis B virus (HBV), hepatitis C virus, and HIV. Government agencies recommend testing for these infections in MMT programs, but uptake is limited. We audited infection-related policies and practices of all 14 MMT programs in Philadelphia, Pennsylvania, in 2015. Results were tabulated and compared with the results from a 2010 audit of 10 of 12 MMT programs. The audit focused on which patients are tested, timing and frequency, specific tests ordered, vaccination, and communication of test results. Written policies were nonspecific, offering little guidance on appropriate testing. The principal change in policy between 2010 and 2015 involved adding clearer guidance for communication of results to patients. In 2010 and 2015, all MMT programs tested new patients for hepatitis C virus antibodies, although retesting of existing patients varied. HBV testing increased from 2010 to 2015, though it was not uniform, with 5 programs testing for HBV surface antibodies and 10 programs testing for HBV surface antigens. Six programs assessed hepatitis vaccination status, but only 1 administered vaccines. In 2010, city-sponsored HIV antibody testing was available at all MMT programs. Without this program in 2015, few MMT programs conducted HIV testing. Despite limited hepatitis and HIV screening in MMT programs nationally, this study shows that testing can be incorporated into routine procedures. MMT programs are positioned to play an integral role in the identification of patients with chronic infections, but additional guidance and resources are required to maximize their impact.

Protective Vaccination against Papillomavirus-Induced Skin Tumors under Immunocompetent and Immunosuppressive Conditions: A Preclinical Study Using a Natural Outbred Animal Model

PubMed Central

Vinzón, Sabrina E.; Braspenning-Wesch, Ilona; Müller, Martin; Geissler, Edward K.; Nindl, Ingo; Gröne, Hermann-Josef

2014-01-01

Certain cutaneous human papillomaviruses (HPVs), which are ubiquitous and acquired early during childhood, can cause a variety of skin tumors and are likely involved in the development of non-melanoma skin cancer, especially in immunosuppressed patients. Hence, the burden of these clinical manifestations demands for a prophylactic approach. To evaluate whether protective efficacy of a vaccine is potentially translatable to patients, we used the rodent Mastomys coucha that is naturally infected with Mastomys natalensis papillomavirus (MnPV). This skin type papillomavirus induces not only benign skin tumours, such as papillomas and keratoacanthomas, but also squamous cell carcinomas, thereby allowing a straightforward read-out for successful vaccination in a small immunocompetent laboratory animal. Here, we examined the efficacy of a virus-like particle (VLP)-based vaccine on either previously or newly established infections. VLPs raise a strong and long-lasting neutralizing antibody response that confers protection even under systemic long-term cyclosporine A treatment. Remarkably, the vaccine completely prevents the appearance of benign as well as malignant skin tumors. Protection involves the maintenance of a low viral load in the skin by an antibody-dependent prevention of virus spread. Our results provide first evidence that VLPs elicit an effective immune response in the skin under immunocompetent and immunosuppressed conditions in an outbred animal model, irrespective of the infection status at the time of vaccination. These findings provide the basis for the clinical development of potent vaccination strategies against cutaneous HPV infections and HPV-induced tumors, especially in patients awaiting organ transplantation. PMID:24586150

78 FR 62427 - TRICARE; Removal of the Prohibition To Use Addictive Drugs in the Maintenance Treatment of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

... addictive potential, for a drug of addiction when medically necessary and appropriate as part of a... assisted treatment, to include drug maintenance involving substitution of a therapeutic drug with addiction potential, for a drug of addiction, is now generally accepted by qualified professionals to be reasonable...

Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy.

PubMed

Lund, L; Henmar, H; Würtzen, P A; Lund, G; Hjortskov, N; Larsen, J N

2007-04-01

Specific immunotherapy with intact allergen vaccine is a well-documented treatment for allergic diseases. Different vaccine formulations are currently commercially available, the active ingredient either being intact allergens or chemically modified allergoids. The rationale behind allergoids is to decrease allergenicity while maintaining immunogenicity. However, data from the German health authorities based on reporting of adverse events over a 10-year period did not indicate increased safety of allergoids over intact allergens. The objective of this study was to investigate the effect of chemical modification on allergenicity and immunogenicity comparing four commercial allergoid products for birch pollen immunotherapy with an intact allergen vaccine. Solid-phase IgE inhibition and histamine release assays were selected as model systems for allergenicity, and a combination of human T cell proliferation and IgG titres following mouse immunizations were used to address the immunogenicity of the intact allergen vaccine and the four allergoids. In all assays, the products were normalized with respect to the manufacturer's recommended maintenance dose. IgE inhibition experiments showed a change in epitope composition comparing intact allergen vaccine with allergoid. One allergoid product induced enhanced histamine release compared to the intact allergens, while the other three allergoids showed reduced release. Standard T cell stimulation assays using lines from allergic patients showed a reduced response for all allergoids compared with the intact allergen vaccine regardless of the cell type used for antigen presentation. All allergoids showed reduced capacity to induce allergen-specific IgG responses in mice. While some allergoids were associated with reduced allergenicity, a clear reduction in immunogenicity was observed for all allergoid products compared with the intact allergen vaccine, and the commercial allergoids tested therefore do not fulfil the allergoid

Can We Translate Vitamin D Immunomodulating Effect on Innate and Adaptive Immunity to Vaccine Response?

PubMed Central

Lang, Pierre Olivier; Aspinall, Richard

2015-01-01

Vitamin D (VitD), which is well known for its classic role in the maintenance of bone mineral density, has now become increasingly studied for its extra-skeletal roles. It has an important influence on the body’s immune system and modulates both innate and adaptive immunity and regulates the inflammatory cascade. In this review our aim was to describe how VitD might influence immune responsiveness and its potential modulating role in vaccine immunogenicity. In the first instance, we consider the literature that may provide molecular and genetic support to the idea that VitD status may be related to innate and/or adaptive immune response with a particular focus on vaccine immunogenicity and then discuss observational studies and controlled trials of VitD supplementation conducted in humans. Finally, we conclude with some knowledge gaps surrounding VitD and vaccine response, and that it is still premature to recommend “booster” of VitD at vaccination time to enhance vaccine response. PMID:25803545

Dengue vaccine development: strategies and challenges.

PubMed

Ramakrishnan, Lakshmy; Pillai, Madhavan Radhakrishna; Nair, Radhakrishnan R

2015-03-01

Infection with dengue virus may result in dengue fever or a more severe outcome, such as dengue hemorrhagic syndrome/shock. Dengue virus infection poses a threat to endemic regions for four reasons: the presence of four serotypes, each with the ability to cause a similar disease outcome, including fatality; difficulties related to vector control; the lack of specific treatment; and the nonavailability of a suitable vaccine. Vaccine development is considered challenging due to the severity of the disease observed in individuals who have acquired dengue-specific immunity, either passively or actively. Therefore, the presence of vaccine-induced immunity against a particular serotype may prime an individual to severe disease on exposure to dengue virus. Vaccine development strategies include live attenuated vaccines, chimeric, DNA-based, subunit, and inactivated vaccines. Each of the candidates is in various stages of preclinical and clinical development. Issues pertaining to selection pressures, viral interaction, and safety still need to be evaluated in order to induce a complete protective immune response against all four serotypes. This review highlights the various strategies that have been employed in vaccine development, and identifies the obstacles to producing a safe and effective vaccine.

Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

NASA Astrophysics Data System (ADS)

Payne, Richard; McDonald, David; Byrne, Scott

2015-10-01

Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

Protection of yearling ponies against Strongylus vulgaris by foalhood vaccination.

PubMed

Klei, T R; French, D D; Chapman, M R; McClure, J R; Dennis, V A; Taylor, H W; Hutchinson, G W

1989-06-01

The long-term efficacy of an irradiation attenuated larval (L3) vaccine against Strongylus vulgaris was tested in ponies which were reared on pasture. Prior to foaling, mares were divided into two groups. One group of mares and foals received regular (eight weekly) treatment with ivermectin and the second group remained untreated. Half the foals in each pasture group were vaccinated at eight to ten weeks of age. Foals were weaned at three to four months of age and maintained on separate pastures. At eight to ten months of age, ponies were placed in box stalls and half of each treatment group were challenged with S. vulgaris (5 x 1000 L3). Clinical signs and lesions typical of acute verminous arteritis were found at necropsy in the ivermectin treated non-vaccinated challenged yearlings. Ivermectin treated vaccinated challenged yearlings did not show these clinical signs, had markedly reduced to absent arterial lesions and showed an 89 per cent reduction in arterial larval burdens post mortem. Significant differences in clinical signs, arterial lesions or arterial larval burdens were not seen between vaccinated and non-vaccinated foals reared without benefit of ivermectin treatment.

Asphalt pavement maintenance field handbook

DOT National Transportation Integrated Search

2001-04-01

This field manual provides guidelines for preventive asphalt pavement maintenance techniques for a variety of distresses and conditions. It covers: 1. crack treatments (clean and seal, rout and seal, full-depth crack repair); 2. surface treatments (f...

Some Preliminary Results on an SEIARD Epidemic Model with Vaccination and Antiviral Treatment Controls and Dead-Infective Culling Action

NASA Astrophysics Data System (ADS)

De la Sen, M.; Nistal, R.; Alonso-Quesada, S.; Garrido, A. J.

2016-08-01

This paper studies the non-negativity and stability properties of the solutions of a newly proposed SEIADR model which incorporates asymptomatic and dead-infective subpopulations to those defining the standard SEIR model and, in parallel, it incorporates feedback vaccination and antiviral treatment controls.

Effect of live attenuated vaccines on the course of experimental allergic encephalomyelitis. A pilot study.

PubMed

Caspary, E A

1977-01-01

The clinical severity of EAE is enhanced by pre-treatment with distemper, measles and BCG vaccine, measles vaccine gives a more severe onset of disease. Rubella vaccine and TAB leads to mild disease which recurs on re-treatment with the appropriate vaccine. These findings and their possible significance in MS are briefly discussed.

Efficacy and Safety of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults with Schizophrenia: a Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Fleischhacker, W Wolfgang; Hobart, Mary; Ouyang, John; Forbes, Andy; Pfister, Stephanie; McQuade, Robert D; Carson, William H; Sanchez, Raymond; Nyilas, Margareta; Weiller, Emmanuelle

2017-01-01

Brexpiprazole has previously demonstrated efficacy in acute schizophrenia trials. The objective of this trial was to assess the efficacy, safety, and tolerability of maintenance treatment with brexpiprazole in adults with schizophrenia. Patients with an acute exacerbation of psychotic symptoms were converted to brexpiprazole (1-4mg/d) over 1 to 4 weeks and entered a single-blind stabilization phase. Those patients who met stability criteria for 12 weeks were randomized 1:1 to double-blind maintenance treatment with either brexpiprazole (at their stabilization dose) or placebo for up to 52 weeks. The primary efficacy endpoint was the time from randomization to impending relapse. Safety and tolerability were also assessed. A total of 524 patients were enrolled, 202 of whom were stabilized on brexpiprazole and randomized to brexpiprazole (n=97) or placebo (n=105). Efficacy was demonstrated at a prespecified interim analysis (conducted after 45 events), and so the trial was terminated early. The final analysis showed that time to impending relapse was statistically significantly delayed with brexpiprazole treatment compared with placebo (P<.0001, log-rank test). The hazard ratio for the final analysis was 0.292 (95% confidence interval: 0.156, 0.548); mean dose at last visit, 3.6mg. The proportion of patients meeting the criteria for impending relapse was 13.5% with brexpiprazole and 38.5% with placebo (P<.0001). During the maintenance phase, the incidence of adverse events was comparable to placebo. or patients with schizophrenia already stabilized on brexpiprazole, maintenance treatment with brexpiprazole was efficacious, with a favorable safety profile. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Burrow dusting or oral vaccination prevents plague-associated prairie dog colony collapse

USGS Publications Warehouse

Tripp, Daniel W.; Rocke, Tonie E.; Runge, Jonathan P.; Abbott, Rachel C.; Miller, Michael W.

2017-01-01

Plague impacts prairie dogs (Cynomys spp.), the endangered black-footed ferret (Mustela nigripes) and other sensitive wildlife species. We compared efficacy of prophylactic treatments (burrow dusting with deltamethrin or oral vaccination with recombinant “sylvatic plague vaccine” [RCN-F1/V307]) to placebo treatment in black-tailed prairie dog (C. ludovicianus) colonies. Between 2013 and 2015, we measured prairie dog apparent survival, burrow activity and flea abundance on triplicate plots (“blocks”) receiving dust, vaccine or placebo treatment. Epizootic plague affected all three blocks but emerged asynchronously. Dust plots had fewer fleas per burrow (P < 0.0001), and prairie dogs captured on dust plots had fewer fleas (P < 0.0001) than those on vaccine or placebo plots. Burrow activity and prairie dog density declined sharply in placebo plots when epizootic plague emerged. Patterns in corresponding dust and vaccine plots were less consistent and appeared strongly influenced by timing of treatment applications relative to plague emergence. Deltamethrin or oral vaccination enhanced apparent survival within two blocks. Applying insecticide or vaccine prior to epizootic emergence blunted effects of plague on prairie dog survival and abundance, thereby preventing colony collapse. Successful plague mitigation will likely entail strategic combined uses of burrow dusting and oral vaccination within large colonies or colony complexes.

[Vaccinations and malaria prophylaxis for international travelers].

PubMed

Alberer, Martin; Löscher, Thomas

2015-05-01

The prevention of infectious diseases by vaccination and by counselling about malaria prophylaxis is a central aspect of travel medicine. Besides mandatory vaccinations required for entry to certain countries various vaccinations may be indicated depending on destination and type of travel as well as on individual risks of the traveler. In addition, pre-travel counselling should always include a check-up of standard vaccinations. Protection against mosquito bites is the basis of malaria prophylaxis. The addition of chemoprophylaxis is warranted in high risk areas. When regular chemoprophylaxis is not applied it is recommended to carry an appropriate antimalarial drug which can be used for emergency stand-by treatment in case of unexplained fever and when medical attention is not available within 24 hours. Travelers should realize that self-treatment is a first-aid measure and that they should still seek medical advice as soon as possible. © Georg Thieme Verlag KG Stuttgart · New York.

Leishmania vaccines: progress and problems.

PubMed

Kedzierski, L; Zhu, Y; Handman, E

2006-01-01

Leishmania are protozoan parasites spread by a sandfly insect vector and causing a spectrum of diseases collectively known as leishmaniasis. The disease is a significant health problem in many parts of the world resulting in an estimated 12 million new cases each year. Current treatment is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective due to the emergence of drug resistance. Leishmaniasis is considered one of a few parasitic diseases likely to be controllable by vaccination. The relatively uncomplicated leishmanial life cycle and the fact that recovery from infection renders the host resistant to subsequent infection indicate that a successful vaccine is feasible. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunisation with protein or DNA vaccines. However, to date no such vaccine is available despite substantial efforts by many laboratories. Advances in our understanding of Leishmania pathogenesis and generation of host protective immunity, together with the completed Leishmania genome sequence open new avenues for vaccine research. The major remaining challenges are the translation of data from animal models to human disease and the transition from the laboratory to the field. This review focuses on advances in anti-leishmania vaccine development over the recent years and examines current problems hampering vaccine development and implementation.

Reviewing the importance of the cold chain in the distribution of vaccines.

PubMed

Purssell, Edward

2015-10-01

Vaccination is an effective public health measure to prevent and control a number of infectious diseases. However, since vaccines are biological products and are sensitive to both heat and cold, they need to be maintained within a narrow range of temperatures, often referred to as the 'cold-chain'. This range, which is between +2°C and +8°C with a target +5°C, does not allow for refreezing or storage at room temperature. This paper discusses the importance of the cold chain, what should be done both to maintain it, and the actions to be taken, should a break be noted. It is important to note the product information supplied with vaccines, which is taken from the summary of product characteristics that forms part of the licensing requirements for each vaccine, and which will state how it should be stored. Using a vaccine that has not been stored according to these instructions constitutes off-label use, for which the individual practitioner must take responsibility. It also emphasises the fragile nature of many public health interventions, maintenance of which require constant vigilance and close cooperation between many groups and individuals.

WHO policy development processes for a new vaccine: case study of malaria vaccines.

PubMed

Milstien, Julie; Cárdenas, Vicky; Cheyne, James; Brooks, Alan

2010-06-24

Recommendations from the World Health Organization (WHO) are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine. The decision-making processes for one malaria intervention and four vaccines were classified through (1) consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP) and Immunization, Vaccines and Biologicals Department (IVB); (2) analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3) interviews with staff of partnerships working toward new vaccine availability; and (4) review and analyses of evidence informing key policy decisions. WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi) and the following vaccine interventions: Haemophilus influenzae type b conjugate vaccine (Hib), pneumococcal conjugate vaccine (PCV), rotavirus vaccine (RV), and human papillomavirus vaccine (HPV), five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations. Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and distribution issues. Although policy issues may be more complex for future vaccines

Levels of diphtheria and tetanus specific IgG of Portuguese adult women, before and after vaccination with adult type Td. Duration of immunity following vaccination

PubMed Central

Gonçalves, Guilherme; Santos, Maria Augusta; Frade, João Graça; Cunha, José Saraiva

2007-01-01

Background The need for tetanus toxoid decennial booster doses has been questioned by some experts. Several counter arguments have been presented, supporting the maintenance of decennial adult booster doses with tetanus and diphtheria toxoids (adult formulation of the vaccine: Td). This study aimed to evaluate the use of Td in Portuguese adult women under routine conditions. For that purpose we selected a group of women 30+ years of age to which vaccination was recommended. We intended to know if pre-vaccination antibody concentrations were associated with factors as age at first and last vaccination, number of doses and time since last revaccination. We also intended to assess the serological efficacy of Td booster. Methods Following the Portuguese guidelines 100 women were vaccinated with Td. Antitetanus toxin IgG (ATT IgG) and antidiphtheria toxin IgG (ADT IgG) levels were measured (mIU/ml) in 100 pre-vaccination and 91 post-vaccination sera. Detailed vaccination records were available from 88 participants. Results Twenty-two women (Group A) began vaccination with DPT/DT in their early childhood and their pre-vaccination ATT IgG levels increased with the number of doses received (p = 0.022) and decreased with time since last vaccination (p = 0.016). Among the 66 women who began vaccination in adolescence and adulthood (Group B), with monovalent TT, ATT IgG levels decreased with age at first dose (p < 0.001) and with time since last vaccination (p = 0.041). In Group A, antidiphtheria toxin IgG kinetics was very similar to that observed for ATT IgG. Among women not vaccinated with diphtheria toxoid, ADT IgG levels decreased with age. Serological response to both components of Td was good but more pronounced for ATT IgG. Conclusion Our study suggests that, to protect against tetanus, there is no need to administer decennial boosters to the Portuguese adults who have complied with the childhood/adolescent schedule (6 doses of tetanus toxoid). The adult booster

Vaccinating parents experience vaccine anxiety too.

PubMed

Luthy, Karlen E; Beckstrand, Renea L; Asay, Whitney; Hewett, Carly

2013-12-01

To identify common causes of parental anxiety regarding childhood vaccinations among parents who vaccinate. Another purpose was to seek recommendations for healthcare providers to help parents overcome their anxiety when their children are immunized. Four 1-h focus groups were conducted, each consisting of 8-10 parents. Each focus group discussion was conducted by a moderator and an assistant moderator. The moderator facilitated discussion while the assistant moderator took notes. Each session was recorded on video. The data were transcribed and analyzed for themes. Parents identifying themselves as being compliant with childhood vaccination requirements reported anxiety that can be divided into five major themes: parental anxiety prior to vaccination, parental anxiety during the vaccination, parental anxiety after the vaccination, parental suggestions for healthcare providers, and informational issues. Making minor changes in office policies may help alleviate some parental anxiety regarding vaccinations. Providers should also create lists of credible sources about vaccination information. Because the cause of vaccine-related parental anxiety varies, targeted education is necessary to relieve common causes of vaccine anxiety, even among parents who vaccinate. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

ALA-PDT mediated DC vaccine for skin squamous cell carcinoma

NASA Astrophysics Data System (ADS)

Ji, Jie; Fan, Zhixia; Zhou, Feifan; Wang, Xiaojie; Shi, Lei; Zhang, Haiyan; Wang, Peiru; Yang, Degang; Zhang, Linglin; Wang, Xiuli; Chen, Wei R.

2015-03-01

Dendritic cell (DC) based vaccine has emerged as a promising immunotherapy for cancers. However, most DC vaccines so far have only achieved limited success in cancer treatment. Photodynamic therapy (PDT), an established cancer treatment strategy, can cause immunogenic apoptosis to induce an effective antitumor immune response. In this study, we developed a DC-based cancer vaccine using immunogenic apoptotic tumor cells induced by 5-aminolevulinic acid (ALA) mediated PDT. The maturation of DCs induced by PDT-treated apoptotic cells was evaluated. The anti-tumor immunity of ALA-PDT-DC vaccine was tested with mouse model. We observed the maturations of DCs potentiated by ALA-PDT treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, DC80, and CD86), and functional maturation (enhanced capability to secret INF-Υ and IL-12). ALA-PDT-DC vaccine mediated by apoptotic cells provided protection against tumor in mice, far stronger than that of DC vaccine obtained from freeze/thaw treated tumor cells. Our results indicate that immunogenic apoptotic tumor cells can be more effective in enhancing DC-based cancer vaccine, which could improve the clinical application of PDT- DC vaccines.

The elusive HIV vaccine: an update on the politics, propaganda and scientific barriers in the search for a safe and effective HIV vaccine.

PubMed

Allen, D

1999-01-01

An update is provided on the barriers confronting the development of an effective HIV vaccine. These issues include political and organizational problems, inadequate research funding, pharmaceutical company reluctance to do vaccine research, and the scientific and testing complexities that must be overcome. Two preventive vaccines (Wyeth-Ayerst DNA and AIDSVAX), and two treatment vaccines (Wyeth-Ayerst DNA and Remune) currently in human trials in the United States are described, along with the rationale behind them.

Seasonal vaccination against malaria: a potential use for an imperfect malaria vaccine.

PubMed

Greenwood, Brian; Dicko, Alassane; Sagara, Issaka; Zongo, Issaka; Tinto, Halidou; Cairns, Matthew; Kuepfer, Irene; Milligan, Paul; Ouedraogo, Jean-Bosco; Doumbo, Ogobara; Chandramohan, Daniel

2017-05-02

In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers. Furthermore, there is a risk of the emergence in the future of resistance to the drugs, sulfadoxine-pyrimethamine and amodiaquine, that are currently being used for SMC. Substantial progress has been made in the development of malaria vaccines during the past decade and one malaria vaccine, RTS,S/AS01, has received a positive opinion from the European Medicines Authority and will soon be deployed in large-scale, pilot implementation projects in sub-Saharan Africa. A characteristic feature of this vaccine, and potentially of some of the other malaria vaccines under development, is that they provide a high level of efficacy during the period immediately after vaccination, but that this wanes rapidly, perhaps because it is difficult to develop effective immunological memory to malaria antigens in subjects exposed previously to malaria infection. A potentially effective way of using malaria vaccines with high initial efficacy but which provide only a short period of protection could be annual, mass vaccination campaigns shortly before each malaria transmission season in areas where malaria transmission is confined largely to a few months of the year.

Vaccine decision-making begins in pregnancy: Correlation between vaccine concerns, intentions and maternal vaccination with subsequent childhood vaccine uptake.

PubMed

Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H

2017-08-12

Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-value<0.001). 66% of mothers reported receiving enough information during pregnancy on childhood vaccination. In the post delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy

Emergency physicians' perspectives on smallpox vaccination.

PubMed

Kwon, Nancy; Raven, Maria C; Chiang, William K; Moran, Gregory J; Jui, Jon; Carter, Richard A; Goldfrank, Lewis

2003-06-01

To evaluate emergency physician (EP) attitudes toward smallpox vaccination, the treatment of patients with suspected smallpox, and the threat of a bioterrorist attack. This was a prospective study utilizing a standardized survey instrument that was distributed on November 16, 2002, and collected by February 1, 2003. EPs from a sample of 50 accredited emergency medicine programs were surveyed regarding their perspectives on smallpox vaccination. A total of 989 surveys were collected from 42 emergency medicine programs. Of the respondents, 43.4% would currently volunteer for smallpox vaccination. EPs previously vaccinated against smallpox were 1.46 times more likely to volunteer for vaccination (95% CI = 1.14 to 1.93). EPs who believed they were at risk for complications were less than half as likely to volunteer for vaccination. EPs who perceived a significant risk of a bioterrorist attack were 2.7 times more likely to volunteer for the vaccine compared with those who thought the risk was minimal (95% CI = 2.06 to 3.47). Of the respondents, 34.4% believed the risks of the vaccination outweighed the benefits, 33% did not, and 32.6% were unsure. Currently, fewer than half of EPs surveyed would volunteer for smallpox vaccination. Factors associated with a willingness to be vaccinated include previous smallpox vaccination and the perceived threat of a bioterrorist attack. The variation in EP attitudes toward smallpox vaccination may be due to uncertain risk-to-benefit ratio. The opinions and actions of EPs may be influential on current and future government policy and public opinion.

Achieving stable remission with maintenance electroconvulsive therapy in a patient with treatment-resistant schizophrenia

PubMed Central

Moeller, Sebastian; Kalkwarf, Neele; Lücke, Caroline; Ortiz, Diana; Jahn, Sonja; Först, Christiane; Braun, Niclas; Philipsen, Alexandra; Müller, Helge H.O.

2017-01-01

Abstract Rationale: Up to one third of all schizophrenic patients are classified as having treatment-resistant schizophrenia (TRS). This subgroup faces remarkable medical and psychosocial damages, and pharmacotherapy is often limited due to nonresponse and/or side effects. Maintenance electroconvulsive therapy (M-ECT) might be effective in TRS. Patient concerns: We present a case of a 26-year-old male patient with a TRS. Diagnoses: He received a treatment series of ECT sessions and a course of 24 M-ECTs. Interventions: The entire treatment was tolerated without significant side effects. Outcomes: Moreover, the Psychotic Symptom Rating Scale (PSYRATS) scores for both positive and negative symptoms decreased and remained stable over the course of M-ECT. Lessons: Because of the remarkable improvement in the negative and positive symptom clusters, we propose systematic examinations in the field of M-ECT in TRS patients. These studies should integrate long-term outcome and tolerance measurements, gaining insight into the optimal duration of treatment for this indication. PMID:29310360

Radiation and Anti-Cancer Vaccines: A Winning Combination.

PubMed

Cadena, Alexandra; Cushman, Taylor R; Anderson, Clark; Barsoumian, Hampartsoum B; Welsh, James W; Cortez, Maria Angelica

2018-01-30

The emerging combination of radiation therapy with vaccines is a promising new treatment plan in the fight against cancer. While many cancer vaccines such as MUC1, p53 CpG oligodeoxynucleotide, and SOX2 may be great candidates for antitumor vaccination, there still remain many investigations to be done into possible vaccine combinations. One fruitful partnership that has emerged are anti-tumor vaccines in combination with radiation. Radiation therapy was previously thought to be only a tool for directly or indirectly damaging DNA and therefore causing cancer cell death. Now, with much preclinical and clinical data, radiation has taken on the role of an in situ vaccine. With both cancer vaccines and radiation at our disposal, more and more studies are looking to combining vaccine types such as toll-like receptors, viral components, dendritic-cell-based, and subunit vaccines with radiation. While the outcomes of these combinatory efforts are promising, there is still much work to be covered. This review sheds light on the current state of affairs in cancer vaccines and how radiation will bring its story into the future.

Combined Immunosuppression Impairs Immunogenicity to Tetanus and Pertussis Vaccination Among Patients with Inflammatory Bowel Disease.

PubMed

Dezfoli, Seper; Horton, Henry A; Thepyasuwan, Nattapaun; Berel, Dror; Targan, Stephan R; Vasiliauskas, Eric A; Dubinsky, Marla; Shih, David Q; Kaur, Manreet; McGovern, Dermot P B; Ippoliti, Andrew; Feldman, Edward J; Melmed, Gil Y

2015-08-01

Pertussis epidemics have recently emerged across the United States, prompting broad public health recommendations for adult Tdap vaccination (tetanus, diphtheria, acellular pertussis). The impact of immunosuppressive regimens for inflammatory bowel disease (IBD) on vaccine responses to the Tdap vaccine is not known. We performed a prospective controlled trial between April 2011 and March 2012. Adults with IBD were consecutively stratified based on therapeutic regimen into one of 5 groups: A: no IBD therapy or 5-aminosalicylates alone; B: maintenance biologic monotherapy; C: maintenance immunomodulator monotherapy; D: combined biologic and immunomodulator therapy; and E: healthy age-matched controls. Subjects received Tdap, and serum antibody levels against tetanus toxoid, pertussis toxoid, and filamentous hemagglutinin (FHA) were drawn just before and approximately 4 weeks after vaccination. The primary outcome was the booster response rate to each antigen. Secondary outcomes included the differences in pregeometric and postgeometric mean titers. A total of 98 subjects enrolled, and 84 completed the study. Tetanus response rates were 55%, 56%, 40%, 27%, and 63% across groups A to E, respectively. Group D rates were lower than those of group B (P = 0.02). Postvaccination pertussis toxoid responses were 59%, 72%, 47%, 45%, and 75%, while FHA responses were 86%, 72%, 80%, 64%, and 75% across groups A to E, respectively. Prevaccination and postvaccination geometric mean titer differences for FHA were lower in group D than those in group A (P = 0.05). Antibody responses to tetanus and pertussis vaccination may be affected by therapeutic drug regimen. Patients with IBD should optimally receive Tdap before starting immunomodulators, particularly when used in combination with anti-tumor necrosis factor alpha agents.

Technology-Enhanced Maintenance of Treatment Gains in Eating Disorders: Efficacy of an Intervention Delivered via Text Messaging

ERIC Educational Resources Information Center

Bauer, Stephanie; Okon, Eberhard; Meermann, Rolf; Kordy, Hans

2012-01-01

Objective: Given the lack of maintenance interventions for eating disorders, a program delivered via the short message service (SMS) and text messaging was developed to support patients after their discharge from inpatient treatment. Method: The efficacy of the intervention was studied in a randomized controlled trial. Additionally, its impact on…

Efficacy and safety of a 12-month treatment with a combination of hydroxypinacolone retinoate and retinol glycospheres as maintenance therapy in acne patients after oral isotretinoin.

PubMed

Bettoli, Vincenzo; Zauli, Stefania; Borghi, Alessandro; Toni, Giulia; Ricci, Michela; Bertoldi, Alberto M; Virgili, Annarosa

2017-02-01

A correct therapeutic management of acne should include a maintenance therapy to prevent recurrences after discontinuing a successful treatment. The aim of this study is to investigate efficacy and safety of a 12-month maintenance treatment with a product, based on Retinsphere technology that combines retinol encapsulated in glycospheres and hydroxypinacolone retinoate (Biretix gel®), to control acne relapse after a treatment with oral isotretinoin (O.I.). The study consisted of 2 phases: active treatment phase (AP) and maintenance phase (MP). In the AP, 40 consecutive patients with moderate facial acne were treated with O.I. until acne remission. Then, the patients entered in the MP and were treated with Biretix gel® once-daily for 12 months. The efficacy parameter was the relapse rate during MP. Thirty-nine patients completed the study. Relapse appeared in 6 patients (15.38%). The new product with Retinsphere technology was well tolerated and none of the subjects complained of adverse events. Our findings seems to provide favorable evidence of the efficacy and the safety of this new product in the maintenance treatment after O.I. in patient with moderate acne. The efficacy is maintain for a period as long as a year after O.I. suspension.

Estimating the cost of cholera-vaccine delivery from the societal point of view: A case of introduction of cholera vaccine in Bangladesh.

PubMed

Sarker, Abdur Razzaque; Islam, Ziaul; Khan, Iqbal Ansary; Saha, Amit; Chowdhury, Fahima; Khan, Ashraful Islam; Cravioto, Alejandro; Clemens, John David; Qadri, Firdausi; Khan, Jahangir A M

2015-09-11

Cholera is a major global public health problem that causes both epidemic and endemic disease. The World Health Organization recommends oral cholera vaccines as a public health tool in addition to traditional prevention practices and treatments in both epidemic and endemic settings. In many developing countries like Bangladesh, the major issue concerns the affordability of this vaccine. In February 2011, a feasibility study entitled, "Introduction of Cholera Vaccine in Bangladesh (ICVB)", was conducted for a vaccination campaign using inactivated whole-cell cholera vaccine (Shanchol) in a high risk area of Mirpur, Dhaka. Empirical data obtained from this trial was used to determine the vaccination cost for a fully immunized person from the societal perspective. A total of 123,661 people were fully vaccinated receiving two doses of the vaccine, while 18,178 people received one dose of the same vaccine. The total cost for vaccine delivery was US$ 492,238 giving a total vaccination cost per fully-vaccinated individual of US$ 3.98. The purchase cost of the vaccine accounted for 58% of the overall cost of vaccination. Attempts to reduce the per-dose cost of the vaccine are likely to have a large impact on the cost of similar vaccination campaigns in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Rabies vaccines: Current status and prospects for development].

PubMed

Starodubova, E S; Preobrazhenskaia, O V; Kuzmenko, Y V; Latanova, A A; Yarygina, E I; Karpov, V L

2015-01-01

Rabies is an infectious disease among humans and animals that remains incurable, despite its longstanding research history. The only way to prevent the disease is prompt treatment, including vaccination as an obligatory component and administration of antirabies immunoglobulin as a supplement. Since the first antirabies vaccination performed in the 19th century, a large number of different rabies vaccines have been developed. Progress in molecular biology and biotechnology enabled the development of effective and safe technologies of vaccine production. Currently, new-generation vaccines are being developed based on recombinant rabies virus strains or on the production of an individual recombinant rabies antigen-glycoprotein (G protein), either as a component of nonpathogenic viruses, or in plants, or in the form of DNA vaccines. In this review, the main modern trends in the development of rabies vaccines have been discussed.

Demonstration of the Use of Remote Temperature Monitoring Devices in Vaccine Refrigerators in Haiti.

PubMed

Cavallaro, Kathleen F; Francois, Jeannot; Jacques, Roody; Mentor, Derline; Yalcouye, Idrissa; Wilkins, Karen; Mueller, Nathan; Turner, Rebecca; Wallace, Aaron; Tohme, Rania A

After the 2010 earthquake, Haiti committed to introducing 4 new antigens into its routine immunization schedule, which required improving its cold chain (ie, temperature-controlled supply chain) and increasing vaccine storage capacity by installing new refrigerators. We tested the feasibility of using remote temperature monitoring devices (RTMDs) in Haiti in a sample of vaccine refrigerators fueled by solar panels, propane gas, or electricity. We analyzed data from 16 RTMDs monitoring 24 refrigerators in 15 sites from March through August 2014. Although 5 of the 16 RTMDs exhibited intermittent data gaps, we identified typical temperature patterns consistent with refrigerator door opening and closing, propane depletion, thermostat insufficiency, and overstocking. Actual start-up, annual maintenance, and annual electricity costs for using RTMDs were $686, $179, and $9 per refrigerator, respectively. In Haiti, RTMD use was feasible. RTMDs could be prioritized for use with existing refrigerators with high volumes of vaccines and new refrigerators to certify their functionality before use. Vaccine vial monitors could provide additional useful information about cumulative heat exposure and possible vaccine denaturation.

Optimizing Benefits of Influenza Virus Vaccination during Pregnancy: Potential Behavioral Risk Factors and Interventions

PubMed Central

Christian, Lisa M.

2014-01-01

Pregnant women and infants are at high risk for complications, hospitalization, and death due to influenza. It is well-established that influenza vaccination during pregnancy reduces rates and severity of illness in women overall. Maternal vaccination also confers antibody protection to infants via both transplacental transfer and breast milk. However, as in the general population, a relatively high proportion of pregnant women and their infants do not achieve protective antibody levels against influenza virus following maternal vaccination. Behavioral factors, particularly maternal weight and stress exposure, may affect initial maternal antibody responses, maintenance of antibody levels over time (i.e., across pregnancy), as well as the efficiency of transplacental antibody transfer to the fetus. Conversely, behavioral interventions including acute exercise and stress reduction can enhance immune protection following vaccination. Such behavioral interventions are particularly appealing in pregnancy because they are safe and non-invasive. The identification of individual risk factors for poor responses to vaccines and the application of appropriate interventions represent important steps towards personalized health care. PMID:24709586

Development and Initial Testing of Messages to Encourage Tuberculosis Testing and Treatment Among Bacille Calmette-Guerin (BCG) Vaccinated Persons

PubMed Central

Galindo-Gonzalez, Sebastian; Irani, Tracy A.

2017-01-01

Misperceptions surrounding the Bacille Calmette-Guerin (BCG) vaccine can lead some vaccinated individuals to resist being tested and treated for tuberculosis (TB). Educational messages to best explain the risk of TB to BCG-vaccinated, Hispanic persons were systematically developed and tested. First, TB program staff provided messages they considered effective. These were analyzed and validated by TB experts, and then presented in group interviews initially to foreign-born Hispanic persons with a TB diagnosis, and then persons without a prior TB diagnosis. Based on interviewees’ feedback, preferred statements were used to develop one long and three short comprehensive messages. One-on-one interviews were conducted with Hispanic persons to assess the saliency of the comprehensive educational messages. Participants preferred messages that were gain or positively-framed and explained that BCG does not confer lifelong protection against TB. Participants confirmed the messages would likely have a positive impact on patient decisions to undergo TB testing and treatment. PMID:24141428

Is freezing in the vaccine cold chain an ongoing issue? A literature review.

PubMed

Hanson, Celina M; George, Anupa M; Sawadogo, Adama; Schreiber, Benjamin

2017-04-19

Vaccine exposure to temperatures below recommended ranges in the cold chain may decrease vaccine potency of freeze-sensitive vaccines leading to a loss of vaccine investments and potentially places children at risk of contracting vaccine preventable illnesses. This literature review is an update to one previously published in 2007 (Matthias et al., 2007), analyzing the prevalence of vaccine exposure to temperatures below recommendations throughout various segments of the cold chain. Overall, 45 studies included in this review assess temperature monitoring, of which 29 specifically assess 'too cold' temperatures. The storage segments alone were evaluated in 41 articles, 15 articles examined the transport segment and 4 studied outreach sessions. The sample size of the studies varied, ranging from one to 103 shipments and from three to 440 storage units. Among reviewed articles, the percentage of vaccine exposure to temperatures below recommended ranges during storage was 33% in wealthier countries and 37.1% in lower income countries. Vaccine exposure to temperatures below recommended ranges occurred during shipments in 38% of studies from higher income countries and 19.3% in lower income countries. This review highlights continuing issues of vaccine exposure to temperatures below recommended ranges during various segments of the cold chain. Studies monitoring the number of events vaccines are exposed to 'too cold' temperatures as well as the duration of these events are needed. Many reviewed studies emphasize the lack of knowledge of health workers regarding freeze damage of vaccines and how this has an effect on temperature monitoring. It is important to address this issue by educating vaccinators and cold chain staff to improve temperature maintenance and supply chain management, which will facilitate the distribution of potent vaccines to children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Human papillomavirus vaccines and vaccine implementation.

PubMed

de Sanjosé, Silvia; Alemany, Laia; Castellsagué, Xavier; Bosch, F Xavier

2008-11-01

Countries are now challenged by the rapid development of vaccines aimed at the primary prevention of infections. In the years to come, several vaccines will need to be considered as potential candidates in routine immunization programs. Recently, two new vaccines against two/four types of human papillomavirus (HPV) have been commercialized. Bivalent HPV 16 and 18 (Cervarix) and quadrivalent HPV 6, 11, 16 and 18 (Gardasil) vaccines are now extensively used in some countries. These vaccines will prevent infection and long-running complications, such as cervical cancer, other HPV-related cancers and genital warts (for the quadrivalent vaccine). The beneficial effect of these vaccines will be largely observed in women. This article summarizes the burden of HPV preventable disease worldwide and briefly describes the impact of secondary prevention and the most relevant aspects of the current available vaccines, their efficacy and safety. Finally, some major aspects that are likely to impact the introduction of these vaccines around the world are outlined, with particular emphasis on developing countries.

Vaccination against Alzheimer disease

PubMed Central

Fettelschoss, Antonia; Zabel, Franziska; Bachmann, Martin F

2014-01-01

Alzheimer disease is a devastating chronic disease without adequate therapy. More than 10 years ago, it was demonstrated in transgenic mouse models that vaccination may be a novel, disease-modifying therapy for Alzheimer. Subsequent clinical development has been a roller-coaster with some positive and many negative news. Here, we would like to summarize evidence that next generation vaccines optimized for old people and focusing on patients with mild disease stand a good chance to proof efficacious for the treatment of Alzheimer. PMID:24535580

Employment-based abstinence reinforcement as a maintenance intervention for the treatment of cocaine dependence: a randomized controlled trial.

PubMed

DeFulio, Anthony; Donlin, Wendy D; Wong, Conrad J; Silverman, Kenneth

2009-09-01

Due to the chronic nature of cocaine dependence, long-term maintenance treatments may be required to sustain abstinence. Abstinence reinforcement is among the most effective means of initiating cocaine abstinence. Practical and effective means of maintaining abstinence reinforcement programs over time are needed. To determine whether employment-based abstinence reinforcement can be an effective long-term maintenance intervention for cocaine dependence. Participants (n = 128) were enrolled in a 6-month job skills training and abstinence initiation program. Participants who initiated abstinence, attended regularly and developed needed job skills during the first 6 months were hired as operators in a data entry business and assigned randomly to an employment-only (control, n = 24) or abstinence-contingent employment (n = 27) group. A non-profit data entry business. Participants Unemployed welfare recipients who used cocaine persistently while enrolled in methadone treatment in Baltimore. Abstinence-contingent employment participants received 1 year of employment-based contingency management, in which access to employment was contingent upon provision of drug-free urine samples under routine and then random drug testing. If a participant provided drug-positive urine or failed to provide a mandatory sample, then that participant received a temporary reduction in pay and could not work until urinalysis confirmed recent abstinence. Cocaine-negative urine samples at monthly assessments across 1 year of employment. During the 1 year of employment, abstinence-contingent employment participants provided significantly more cocaine-negative urine samples than employment-only participants [79.3% and 50.7%, respectively; P = 0.004, odds ratio (OR) = 3.73, 95% confidence interval (CI) = 1.60-8.69]. Conclusions Employment-based abstinence reinforcement that includes random drug testing is effective as a long-term maintenance intervention, and is among the most promising treatments

Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study.

PubMed

Findling, Robert L; Johnson, Jacqueline L; McClellan, Jon; Frazier, Jean A; Vitiello, Benedetto; Hamer, Robert M; Lieberman, Jeffrey A; Ritz, Louise; McNamara, Nora K; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

2010-06-01

To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. Of the 116 youths randomized in the acute trial, 54 entered maintenance treatment (molindone, n = 20; olanzapine, n = 13; risperidone, n = 21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (n = 15), inadequate efficacy (n = 14), or study nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. Only 12% of youths with early-onset schizophrenia spectrum disorders continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for early-onset schizophrenia spectrum disorders. Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Budget impact analysis of vaccination against Haemophilus influenzae type b as a part of a Pentavalent vaccine in the childhood immunization schedule of Iran.

PubMed

Teimouri, Fatemeh; Kebriaeezadeh, Abbas; Zahraei, Seyed Mohsen; Gheiratian, MohammadMahdi; Nikfar, Shekoufeh

2017-01-14

Health decision makers need to know the impact of the development of a new intervention on the public health and health care costs so that they can plan for economic and financial objectives. The aim of this study was to determine the budget impact of adding Haemophilus influenzae type b (Hib) as a part of a Pentavalent vaccine (Hib-HBV-DTP) to the national childhood immunization schedule of Iran. An excel-based model was developed to determine the costs of including the Pentavalent vaccine in the national immunization program (NIP), comparing the present schedule with the previous one (including separate DTP and hepatitis B vaccines). The total annual costs included the cost of vaccination (the vaccine and syringe) and the cost of Hib treatment. The health outcome was the estimated annual cases of the diseases. The net budget impact was the difference in the total annual cost between the two schedules. Uncertainty about the vaccine effectiveness, vaccination coverage, cost of the vaccine, and cost of the diseases were handled through scenario analysis. The total cost of vaccination during 5 years was $18,060,463 in the previous program and $67,774,786 in the present program. Inclusion of the Pentavalent vaccine would increase the vaccination cost about $49 million, but would save approximately $6 million in the healthcare costs due to reduction of disease cases and treatment costs. The introduction of the Pentavalent vaccine resulted in a net increase in the healthcare budget expenditure across all scenarios from $43.4 million to $50.7 million. The results of this study showed that the inclusion of the Pentavalent vaccine in the NIP of Iran had a significant impact on the health care budget and increased the financial burden on the government. Budget impact of including Pentavalent vaccine in the national immunization schedule of Iranᅟ.

Vaccination in inflammatory bowel disease patients: attitudes, knowledge, and uptake.

PubMed

Malhi, Gurtej; Rumman, Amir; Thanabalan, Reka; Croitoru, Kenneth; Silverberg, Mark S; Hillary Steinhart, A; Nguyen, Geoffrey C

2015-06-01

Immunomodulators and biological agents, used to treat inflammatory bowel disease [IBD], are associated with an increased risk of infection, including vaccine-preventable infections. We assessed patient attitudes towards vaccination, knowledge of vaccine recommendations, and uptake of recommended vaccines. Patients attending IBD clinics completed a self-administered, structured, paper-based questionnaire. We collected demographic data, medical and immunisation history, self-reported patient uptake, knowledge, and perceptions of childhood and adult vaccinations. The prevalence of treatment with biologicals, steroids, thiopurines, and methotrexate among the 300 respondents were 37.3%, 16.0%, 16.0%, and 5.7%, respectively. Self-reported vaccine completion was reported by 45.3% of patients. Vaccination uptake rates were 61.3% for influenza, 10.3% for pneumococcus, 61.0% for hepatitis B, 52.0% for hepatitis A, 26.0% for varicella, 20.7% for meningococcus, 5.3% for herpes zoster, and 11.0% for herpes papilloma virus [females only]. Significant predictors of vaccine completion were annual vaccination review by family physician (odds ratio [OR] = 1.82) or gastroenterologist [OR = 1.72], current steroid use [OR = 1.28], and current or prior treatment with biologicals [OR = 1.42]. The majority of patients reported that the primary responsibility to ensure vaccine completion lies with the patient [41.7%] and the family physician [32.3%]. Uncertainty about indications, fears of side effects, and concerns regarding vaccine safety were the most commonly reported reasons for non-uptake [22.0%, 20.7%, and 5.3%, respectively]. Uptake of recommended vaccines among IBD patients is suboptimal. Annual vaccination reviews by both family physician and gastroenterologist may improve vaccine uptake. Interventions targeted at improving vaccination uptake in IBD patients are needed. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All

Developing an effective breast cancer vaccine.

PubMed

Soliman, Hatem

2010-07-01

Harnessing the immune response in treating breast cancer would potentially offer a less toxic, more targeted approach to eradicating residual disease. Breast cancer vaccines are being developed to effectively train cytotoxic T cells to recognize and kill transformed cells while sparing normal ones. However, achieving this goal has been problematic due to the ability of established cancers to suppress and evade the immune response. A review of the literature on vaccines and breast cancer treatment was conducted, specifically addressing strategies currently available, as well as appropriate settings, paradigms for vaccine development and response monitoring, and challenges with immunosuppression. Multiple issues need to be addressed in order to optimize the benefits offered by breast cancer vaccines. Primary issues include the following: (1) cancer vaccines will likely work better in a minimal residual disease state, (2) clinical trial design for immunotherapy should incorporate recommendations from expert groups such as the Cancer Vaccine Working Group and use standardized immune response measurements, (3) the presently available cancer vaccine approaches, including dendritic cell-based, tumor-associated antigen peptide-based, and whole cell-based, have various pros and cons, (4) to date, no one approach has been shown to be superior to another, and (5) vaccines will need to be combined with immunoregulatory agents to overcome tumor-related immunosuppression. Combining a properly optimized cancer vaccine with novel immunomodulating agents that overcome tumor-related immunosuppression in a well-designed clinical trial offers the best hope for developing an effective breast cancer vaccine strategy.

[Guidelines for vaccination of immunocompromised individuals].

PubMed

Wiedermann, Ursula; Sitte, Harald H; Burgmann, Heinz; Eser, Alexander; Falb, Petra; Holzmann, Heidemarie; Kitchen, Maria; Köller, Marcus; Kollaritsch, Herwig; Kundi, Michael; Lassmann, Hans; Mutz, Ingomar; Pickl, Winfried F; Riedl, Elisabeth; Sibilia, Maria; Thalhammer, Florian; Tucek, Barbara; Zenz, Werner; Zwiauer, Karl

2016-08-01

Immunosuppression of various origins is associated with an increased risk of infection; therefore the prevention of infectious diseases by vaccination is especially important in immunocompromised patients. However, the response to vaccinations is often reduced in these risk groups and the application of live vaccines is contraindicated during immunosuppression.In the following expert statement, recommendations for vaccination were created on the basis of current evidence and theoretical/immunological considerations. A first, general part elaborates on efficacy and safety of vaccinations during immunosuppression, modes of action of immunosuppressive medications and recommended time intervals between immunosuppressive treatments and vaccinations. A core piece of this part is a graduation of immunosuppression into three stages, i. e. no relevant immunosuppression, mild to moderate and severe immunosuppression and the assignment of various medications (including biologicals) to one of those stages; this is followed by an overview of possible and necessary vaccinations in each of those stages.The second part gives detailed vaccination guidelines for common diseases and therapies associated with immunosuppression. Primary immune deficiencies, chronic kidney disease, diabetes mellitus, solid and hematological tumors, hematopoetic stem cell transplantation, transplantation of solid organs, aspenia, rheumatological-, gastroenterologic-, dermatologic-, neurologic diseases, biologicals during pregnancy and HIV infection are dealt with.These vaccination guidelines, compiled for the first time in Austria, aim to be of practical help for physicians to facilitate and improve vaccination coverage in immunocompromised patients and their household members and contact persons.

Vaccination against bubonic and pneumonic plague.

PubMed

Titball, R W; Williamson, E D

2001-07-20

Yersinia pestis is the etiological agent of bubonic and pneumonic plague, diseases which have caused over 200 milllion human deaths in the past. Plague still occurs throughout the world today, though for reasons that are not fully understood pandemics of disease do not develop from these outbreaks. Antibiotic treatment of bubonic plague is usually effective, but pneumonic plague is difficult to treat and even with antibiotic therapy death often results. A killed whole cell plague vaccine has been used in the past, but recent studies in animals have shown that this vaccine offers poor protection against pneumonic disease. A live attenuated vaccine is also available. Whilst this vaccine is effective, it retains some virulence and in most countries it is not considered to be suitable for use in humans. We review here work to develop improved sub-unit and live attenuated vaccines against plague. A sub-unit vaccine based on the F1- and V-antigens is highly effective against both bubonic and pneumonic plague, when tested in animal models of disease. This vaccine has been used to explore the utility of different intranasal and oral delivery systems, based on the microencapsulation or Salmonella delivery of sub-units.

Pharmacokinetic Correlates of the Effects of a Heroin Vaccine on Heroin Self-Administration in Rats

PubMed Central

Raleigh, Michael D.; Pentel, Paul R.; LeSage, Mark G.

2014-01-01

The purpose of this study was to evaluate the effects of a morphine-conjugate vaccine (M-KLH) on the acquisition, maintenance, and reinstatement of heroin self-administration (HSA) in rats, and on heroin and metabolite distribution during heroin administration that approximated the self-administered dosing rate. Vaccination with M-KLH blocked heroin-primed reinstatement of heroin responding. Vaccination also decreased HSA at low heroin unit doses but produced a compensatory increase in heroin self-administration at high unit doses. Vaccination shifted the heroin dose-response curve to the right, indicating reduced heroin potency, and behavioral economic demand curve analysis further confirmed this effect. In a separate experiment heroin was administered at rates simulating heroin exposure during HSA. Heroin and its active metabolites, 6-acetylmorphine (6-AM) and morphine, were retained in plasma and metabolite concentrations were reduced in brain in vaccinated rats compared to controls. Reductions in 6-AM concentrations in brain after vaccination were consistent with the changes in HSA rates accompanying vaccination. These data provide evidence that 6-AM is the principal mediator of heroin reinforcement, and the principal target of the M-KLH vaccine, in this model. While heroin vaccines may have potential as therapies for heroin addiction, high antibody to drug ratios appear to be important for obtaining maximal efficacy. PMID:25536404

Vaccine platforms to control Lassa fever.

PubMed

Lukashevich, Igor S; Pushko, Peter

2016-09-01

Lassa virus (LASV), the most prominent human pathogen of the Arenaviridae, is transmitted to humans from infected rodents and can cause Lassa Fever (LF). The sizeable disease burden in West Africa, numerous imported LF cases worldwide, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. There are no licensed LASV vaccines and the antiviral treatment is limited to an off-label use of ribavirin that is only partially effective. LASV vaccine development is hampered by high cost of biocontainment requirement, the absence of appropriate small animal models, genetic diversity of LASV species, and by high HIV-1 prevalence in LASV endemic areas. Over the past 15 years several vaccine platforms have been developed. Natural history of LASV and pathogenesis of the disease provide strong justification for replication-competent (RC) vaccine as one of the most feasible approaches to control LF. Development of LASV vaccine candidates based on reassortant, recombinant, and alphavirus replicon technologies is covered in this review. Expert commentary: Two lead RC vaccine candidates, reassortant ML29 and recombinant VSV/LASV, have been successfully tested in non-human primates and have been recommended by international vaccine experts for rapid clinical development. Both platforms have powerful molecular tools to further secure safety, improve immunogenicity, and cross-protection. These platforms are well positioned to design multivalent vaccines to protect against all LASV strains citculatrd in West Africa. The regulatory pathway of Candid #1, the first live-attenuated arenaviral vaccine against Argentine hemorrhagic, will be a reasonable guideline for LASV vaccine efficacy trials.

[Development of Hospital Equipment Maintenance Information System].

PubMed

Zhou, Zhixin

2015-11-01

Hospital equipment maintenance information system plays an important role in improving medical treatment quality and efficiency. By requirement analysis of hospital equipment maintenance, the system function diagram is drawed. According to analysis of input and output data, tables and reports in connection with equipment maintenance process, relationships between entity and attribute is found out, and E-R diagram is drawed and relational database table is established. Software development should meet actual process requirement of maintenance and have a friendly user interface and flexible operation. The software can analyze failure cause by statistical analysis.

Phase I safety and antigenicity of TA-GW: a recombinant HPV6 L2E7 vaccine for the treatment of genital warts.

PubMed

Thompson, H S; Davies, M L; Holding, F P; Fallon, R E; Mann, A E; O'Neill, T; Roberts, J S

1999-01-01

A phase I double-blind, randomized, placebo-controlled study was carried out in healthy subjects to assess the safety and immunogenicity of TA-GW, a recombinant HPV6 L2E7 fusion protein vaccine for the treatment of genital warts. Forty-two healthy male volunteers were randomised to receive three intramuscular injections of either 0, 3, 30 or 300 microg of recombinant L2E7 adsorbed onto Alhydrogel. Two vaccination schedules were compared: weeks 0, 1 and 4 (accelerated schedule) and weeks 0, 4 and 8 (classical schedule). Subjects were monitored for adverse events throughout. Immunogenicity was assessed by measuring L2E7 specific in vitro T cell proliferative responses, production of IFNgamma and IL-5 and serum antibodies. Dose-dependent and long-lived T and B cell immune responses were elicited by TA-GW with both vaccination schedules. In conclusion, TA-GW is both safe, well-tolerated and immunogenic. The results allow the selection of the 300-microg vaccine formulation and accelerated vaccination schedule for phase II trials in patients with genital warts.

Dacarbazine treatment before peptide vaccination enlarges T-cell repertoire diversity of melan-a-specific, tumor-reactive CTL in melanoma patients.

PubMed

Palermo, Belinda; Del Bello, Duilia; Sottini, Alessandra; Serana, Federico; Ghidini, Claudia; Gualtieri, Novella; Ferraresi, Virginia; Catricalà, Caterina; Belardelli, Filippo; Proietti, Enrico; Natali, Pier Giorgio; Imberti, Luisa; Nisticò, Paola

2010-09-15

Combination of chemotherapy and immunotherapy to increase the effectiveness of an antitumor immune response is currently regarded as an attractive antitumor strategy. In a pilot clinical trial, we have recently documented an increase of melanoma antigen A (Melan-A)-specific, tumor-reactive, long-lasting effector-memory CD8(+) T cells after the administration of dacarbazine (DTIC) 1 day before peptide vaccination in melanoma patients. Global transcriptional analysis revealed a DTIC-induced activation of genes involved in the immune response and leukocyte activation. To identify the possible mechanisms underlying this improved immune response, we have compared the endogenous and the treatment-induced anti-Melan-A response at the clonal level in patients treated with the vaccine alone or with DTIC plus vaccine. We report a progressive widening of T-cell receptor (TCR) repertoire diversity, accompanied by high avidity and tumor reactivity, only in Melan-A-specific T-cell clones of patients treated with chemoimmunotherapy, with a trend toward longer survival. Differently, patients treated with vaccine alone showed a tendency to narrowing the TCR repertoire diversity, accompanied by a decrease of tumor lytic activity in one patient. Collectively, our findings indicate that DTIC plus vaccination shapes the TCR repertoire in terms of diversity and antitumor response, suggesting that this combined therapy could be effective in preventing melanoma relapse. ©2010 AACR.

A phase I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome.

PubMed

Hazama, Shoichi; Nakamura, Yusuke; Takenouchi, Hiroko; Suzuki, Nobuaki; Tsunedomi, Ryouichi; Inoue, Yuka; Tokuhisa, Yoshihiro; Iizuka, Norio; Yoshino, Shigefumi; Takeda, Kazuyoshi; Shinozaki, Hirokazu; Kamiya, Akira; Furukawa, Hiroyuki; Oka, Masaaki

2014-03-10

To evaluate the safety of combination vaccine treatment of multiple peptides, phase I clinical trial was conducted for patients with advanced colorectal cancer using five novel HLA-A*2402-restricted peptides, three peptides derived from oncoantigens, ring finger protein 43 (RNF43), 34 kDa-translocase of the outer mitochondrial membrane (TOMM34), and insulin-like growth factor-II mRNA binding protein 3 (KOC1), and the remaining two from angiogenesis factors, vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2. Eighteen HLA- A*2402-positive colorectal cancer patients who had failed to standard therapy were enrolled in this study. 0.5 mg, 1.0 mg or 3.0 mg each of the peptides was mixed with incomplete Freund's adjuvant and then subcutaneously injected at five separated sites once a week. We also examined possible effect of a single site injection of "the cocktail of 5 peptides" on the immunological responses. ELISPOT assay was performed before and after vaccinations in the schedule of every 4 weeks. The vaccine treatment using multiple peptides was well tolerated without any severe treatment-associated systemic adverse events. Dose-dependent induction of peptide-specific cytotoxic T lymphocytes was observed. The single injection of "peptides cocktail" did not diminish the immunological responses. Regarding the clinical outcome, one patient achieved complete response and 6 patients revealed stable disease for 4 to 7 months. The median overall survival time (MST) was 13.5 months. Patients, in which we detected induction of cytotoxic T lymphocytes specific to 3 or more peptides, revealed significantly better prognosis (MST; 27.8 months) than those with poorer immune responses (MST; 3.7 months) (p = 0.032). Our cancer vaccine treatment using multiple peptides is a promising approach for advanced colorectal cancer with the minimum risk of systemic adverse reactions. UMIN-CTR number UMIN000004948.

Civil liberties and the critics of safe vaccination: Australian Vaccination Network Inc v Health Care Complaints Commission [2012] NSWSC 110.

PubMed

Vines, Tim; Faunce, Thomas

2012-09-01

Public immunisation programs have, time and again, demonstrated their effectiveness at reducing mortality and morbidity from vaccine-preventable diseases such as measles and pertussis. Governments, health agencies and almost all health practitioners regard vaccines as safe and cost-effective treatments with a low risk profile. Nevertheless, despite, or perhaps because of, their success, immunisation programs and vaccines have increasingly been questioned by various lobby groups, sceptical of the safety of vaccines and the motives of those who administer them. Whereas the reach of these groups would have once been limited by the cost of postage, the internet has delivered a global audience. The extent to which these anti-vaccination advocates are expected to comply with the ethical and professional standards applied to registered health professionals remains unresolved in Australia. As demonstrated in the case of Australian Vaccination Network Inc v Health Care Complaints Commission [2012] NSWSC 110, the ability of professional oversight bodies to regulate the information promoted by these lobby groups is limited by traditional conceptions of the doctor-patient relationship and the clinical setting in which medical advice is delivered. Acknowledging that vaccines, like all medical treatments, involve some level of risk, this article explores the relationship between the state, parents, family, medical professionals and such lobbyists within a human rights framework, suggesting that most public immunisation programs deliver benefits in "the best interest of the child" that, on balance, provide a good result for the civil liberties of Australians.

Vaccines today, vaccines tomorrow: a perspective.

PubMed

Loucq, Christian

2013-01-01

Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.

Vaccination intervention on epidemic dynamics in networks

NASA Astrophysics Data System (ADS)

Peng, Xiao-Long; Xu, Xin-Jian; Fu, Xinchu; Zhou, Tao

2013-02-01

Vaccination is an important measure available for preventing or reducing the spread of infectious diseases. In this paper, an epidemic model including susceptible, infected, and imperfectly vaccinated compartments is studied on Watts-Strogatz small-world, Barabási-Albert scale-free, and random scale-free networks. The epidemic threshold and prevalence are analyzed. For small-world networks, the effective vaccination intervention is suggested and its influence on the threshold and prevalence is analyzed. For scale-free networks, the threshold is found to be strongly dependent both on the effective vaccination rate and on the connectivity distribution. Moreover, so long as vaccination is effective, it can linearly decrease the epidemic prevalence in small-world networks, whereas for scale-free networks it acts exponentially. These results can help in adopting pragmatic treatment upon diseases in structured populations.

Approaches to Preventative and Therapeutic HIV vaccines

PubMed Central

Gray, Glenda E.; Laher, Fatima; Lazarus, Erica; Ensoli, Barbara; Corey, Lawrence

2016-01-01

Novel strategies are being researched to discover vaccines to prevent and treat HIV-1. Nonefficacious preventative vaccine approaches include bivalent recombinant gp120 alone, HIV gene insertion into an Adenovirus 5 (Ad5) virus vector and the DNA prime/Ad5 boost vaccine regimen. However, the ALVAC-HIV prime/AIDSVAX® B/E gp120 boost regimen showed 31.2% efficacy at 3.5 years, and is being investigated as clade C constructs with an additional boost. Likewise, although multiple therapeutic vaccines have failed in the past, in a non-placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. Monoclonal antibodies for passive immunization or treatment show promise, with VRC01 entering advanced clinical trials. PMID:26985884

Bovine adenovirus-3 as a vaccine delivery vehicle.

PubMed

Ayalew, Lisanework E; Kumar, Pankaj; Gaba, Amit; Makadiya, Niraj; Tikoo, Suresh K

2015-01-15

The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry through animal loss, decreased productivity, treatment expenses and decreased carcass quality. However, some vaccines produced by conventional means are imperfect in many respects including virulence, safety and efficacy. Moreover, there are no vaccines for some animal diseases. Although genetic engineering has provided new ways of producing effective vaccines, the cost of production for veterinary use is a critical criterion for selecting the method of production and delivery of vaccines. The cost effective production and intrinsic ability to enter cells has made adenovirus vectors a highly efficient tool for delivery of vaccine antigens. Moreover, adenoviruses induce both humoral and cellular immune responses to expressed vaccine antigens. Since nonhuman adenoviruses are species specific, the development of animal specific adenoviruses as vaccine delivery vectors is being evaluated. This review summarizes the work related to the development of bovine adenovirus-3 as a vaccine delivery vehicle in animals, particularly cattle. Copyright © 2014 Elsevier Ltd. All rights reserved.

How will transitioning from cytology to HPV testing change the balance between the benefits and harms of cervical cancer screening? Estimates of the impact on cervical cancer, treatment rates and adverse obstetric outcomes in Australia, a high vaccination coverage country.

PubMed

Velentzis, Louiza S; Caruana, Michael; Simms, Kate T; Lew, Jie-Bin; Shi, Ju-Fang; Saville, Marion; Smith, Megan A; Lord, Sarah J; Tan, Jeffrey; Bateson, Deborah; Quinn, Michael; Canfell, Karen

2017-12-15

Primary HPV screening enables earlier diagnosis of cervical lesions compared to cytology, however, its effect on the risk of treatment and adverse obstetric outcomes has not been extensively investigated. We estimated the cumulative lifetime risk (CLR) of cervical cancer and excisional treatment, and change in adverse obstetric outcomes in HPV unvaccinated women and cohorts offered vaccination (>70% coverage in 12-13 years) for the Australian cervical screening program. Two-yearly cytology screening (ages 18-69 years) was compared to 5-yearly primary HPV screening with partial genotyping for HPV16/18 (ages 25-74 years). A dynamic model of HPV transmission, vaccination, cervical screening and treatment for precancerous lesions was coupled with an individual-based simulation of obstetric complications. For cytology screening, the CLR of cervical cancer diagnosis, death and treatment was estimated to be 0.649%, 0.198% and 13.4% without vaccination and 0.182%, 0.056% and 6.8%, in vaccinated women, respectively. For HPV screening, relative reductions of 33% and 22% in cancer risk for unvaccinated and vaccinated women are predicted, respectively, compared to cytology. Without the implementation of vaccination, a 4% increase in treatment risk for HPV versus cytology screening would have been expected, implying a possible increase in pre-term delivery (PTD) and low birth weight (LBW) events of 19 to 35 and 14 to 37, respectively, per 100,000 unvaccinated women. However, in vaccinated women, treatment risk will decrease by 13%, potentially leading to 4 to 41 fewer PTD events and from 2 more to 52 fewer LBW events per 100,000 vaccinated women. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. HPV screening starting at age 25 in populations with

Predictors of accessing antiretroviral therapy among HIV-positive drug users in China's National Methadone Maintenance Treatment Programme.

PubMed

Zhao, Yan; Shi, Cynthia X; McGoogan, Jennifer M; Rou, Keming; Zhang, Fujie; Wu, Zunyou

2015-01-01

The objective of this study was to examine factors that predict antiretroviral therapy (ART) access among eligible, HIV-positive methadone maintenance treatment (MMT) clients. We also tested the hypothesis that sustained MMT participation increases the likelihood of accessing ART. A nation-wide cohort study conducted from 1 March 2004 to 31 December 2011. MMT clients were followed from the time of their enrolment in China's national MMT programme until their death or the study end date. Our cohort comprised 7111 ART-eligible, HIV-positive MMT clients, 49.2% of whom remained ART-naive and 50.8% of whom received ART. Demographic variables, drug use history, MMT programme participation and HIV-related clinical characteristics of study participants who remained naive to ART and those who accessed ART were compared by univariate and multivariable analysis. Predictors of accessing ART among this cohort included being retained in MMT at the time of first meeting ART eligibility [adjusted odds ratio (AOR)=1.84, confidence interval (CI)=1.54-2.21, P<0.001] compared to meeting ART eligibility before entering MMT (AOR=0.98, CI=0.80-1.21, P=0.849) or previously entering MMT and dropping out before meeting ART eligibility. Additional predictors were CD4≤200 cells/μl when ART-eligibility requirement was first met (AOR=1.81, CI=1.61-2.05, P<0.001 compared to CD4=201-350 cells/μl), and being in a stable partner relationship (married/cohabitating: AOR=1.14, CI=1.01-1.28, P=0.030). Retained participation in methadone maintenance treatment increases the likelihood that eligible clients will access antiretroviral therapy. These results highlight the potential benefit of colocalization of methadone maintenance treatment and antiretroviral therapy services in a 'one-stop-shop' model. © 2014 Society for the Study of Addiction.

Vaccines Cold Chain Monitoring: A Cross Sectional Study at Three District In Indonesia

NASA Astrophysics Data System (ADS)

Saraswati, L. D.; Ginandjar, P.; Budiyono; Martini; Udiyono, A.; Kairul

2018-02-01

Vaccine cold chain is a procedure that is used to keep vaccines at a certain temperature. The aim was to describe the vaccine cold chain management of basic immunization program in health centers district. The study design descriptive observational. The samples was Health Centers (HCs); 12 HCs in Sarolangun Jambi Province, 16 HCs in Brebes Central Java Province, and 24 HCs in Temanggung Central Java Provice. Basic immunization vaccines were BCG, DPT-HB-HIB, Polio, and Measles. The results showed proportion of officers graduated from college in Sorolangun, Brebes, and Temanggung were 66.7%, 81.3%, and 52.0% respectively. Proportion of HC that did not have thermometer and fridge freeze was mostly found in Temanggung (52%) and in Sorolangun (91.7%). The heat-sensitive vaccines arranged near the evaporator mostly found in Temanggung (88%), while freeze-sensitive vaccines prepared away of the evaporator mostly in Brebes (100%). Freezer temperature recording chart is not available mostly found in Sorolangun and Brebes (50%), In Sorolangun 41.7% of the officers monitoring 2 times a day and mostly (91.7%) the refrigerator thermostat tape was not isolated. The officers did not perform daily maintenance (50%), weekly (66.7%), and montly (33.3%) mostly found in Sorolangun. From this study we can conclude there is no vaccine immunization program management in Sarolangun, Brebes, and Temanggung that managed according to Ministry of Health Regulations number 42/2013 on the Implementation of immunization. Improvement oversight, control over management of vaccine and management personal, also managing the temperature of the vaccine were recommended.

Therapeutic vaccines for substance dependence.

PubMed

Kosten, Thomas R; Biegel, Diane

2002-10-01

Several immunotherapies are under development for nicotine, cocaine and phencyclidine and a cocaine vaccine has started human trials. These therapies promise a new approach to diseases that have had limited treatment success and tremendous morbidity. Both the cocaine and nicotine addiction immunotherapies have reduced 'relapse' to drug use in animal model systems. To date, the active cocaine vaccine has few side effects and induces considerable antibody titers after active immunization in humans. Studies with the monoclonal phencyclidine immunotherapy provide intriguing evidence of sustained protection for months after single-dose administration. Other immunotherapy may include treatment of drug overdose, prevention of brain or cardiac toxicity and protection of a fetus during pregnancy in a drug abuser.

Impact of Virginia's School-Entry Vaccine Mandate on Human Papillomavirus Vaccination Among 13-17-Year-Old Females.

PubMed

Pierre-Victor, Dudith; Page, Timothy F; Trepka, Mary Jo; Stephens, Dionne P; Li, Tan; Madhivanan, Purnima

2017-03-01

The link between human papillomavirus (HPV) and anogenital cancers is well established in the literature. Many states have passed laws requiring funding for HPV education or vaccination. Mandatory HPV vaccination policies have been considered and passed in several states; yet their effectiveness has not been evaluated. This study sought to assess the impact of Virginia's HPV vaccine mandate for school-entry on HPV vaccine uptake among females aged 13-17 years. Data from the National Immunization Survey-Teen for the 2008-2012 period were used, and 3,203 adolescent females were included in the analysis. We performed difference-in-differences estimation and logistic regression with a policy and period interaction term. Virginia was considered the treatment state, and South Carolina and Tennessee were the comparison states to account for nonpolicy factors that may have affected vaccination rates during the time period considered in the analysis. There was no evidence of an effect of Virginia's HPV vaccine mandate for school-entry on vaccination rates or on physician vaccination recommendation using either the difference-by-differences analysis or the policy and period interaction term in the logistic regression. Physician recommendation was the factor most strongly associated with vaccination in the Virginia-South Carolina analysis (adjusted odds ratio [aOR] = 9.33; 95% confidence interval [CI]: 6.11-14.3) and in the Virginia-Tennessee analysis (aOR = 9.33; 95% CI: 6.11-14.3). Study findings suggest that Virginia's HPV vaccine mandate for school-entry did not lead to a significant increase in HPV vaccination among adolescent females or physician recommendations. However, physician recommendation was the factor most strongly associated with vaccination.

The social support and social network characteristics of smokers in methadone maintenance treatment.

PubMed

de Dios, Marcel Alejandro; Stanton, Cassandra A; Caviness, Celeste M; Niaura, Raymond; Stein, Michael

2013-01-01

Previous studies have shown social support and social network variables to be important factors in smoking cessation treatment. Tobacco use is highly prevalent among individuals in methadone maintenance treatment (MMT). However, smoking cessation treatment outcomes in this vulnerable subpopulation have been poor and social support and social network variables may contribute. The current study examined the social support and social network characteristics of 151 MMT smokers involved in a randomized clinical trial of smoking cessation treatments. Participants were 50% women and 78% Caucasian. A high proportion (57%) of MMT smokers had spouses or partners who smoke and over two-thirds of households (68.5%) included at least one smoker. Our sample was characterized by relatively small social networks, but high levels of general social support and quitting support. The number of cigarettes per day was found to be positively associated with the number of smokers in the social network (r = .239, p < .05) and quitting self-efficacy was negatively associated with partner smoking (r = -.217, p < .001). Findings are discussed in the context of developing smoking cessation interventions that address the influential role of social support and social networks of smokers in MMT.

Use of a GnRH vaccine, GonaCon, for prevention and treatment of adrenocortical disease (ACD) in domestic ferrets.

PubMed

Miller, Lowell A; Fagerstone, Kathleen A; Wagner, Robert A; Finkler, Mark

2013-09-23

Adrenocortical disease (ACD) is a common problem in surgically sterilized, middle-aged to old ferrets (Mustela putorius furo). The adrenal tissues of these ferrets develop hyperplasia, adenomas, or adenocarcinomas, which produce steroid hormones including estradiol, 17-hydroxyprogesterone, and androstenedione. Major clinical signs attributable to overproduction of these hormones are alopecia (hair loss) in both sexes and a swollen vulva in females. Pruritus, muscle atrophy, hind limb weakness, and sexual activity or aggression are also observed in both sexes. Males can develop prostatic cysts, prostatitis, and urethral obstruction. ACD is thought to be linked to continuous and increased LH secretion, due to lack of gonadal hormone feedback in neutered ferrets. This continuous elevated LH acts on adrenal cortex LH receptors, resulting in adrenal hyperplasia or adrenal tumor. This study investigated whether the immunocontraceptive vaccine GonaCon, a GnRH vaccine developed to reduce the fertility of wildlife species and the spread of disease, could prevent or delay onset of ACD and treat alopecia in ferrets with existing ACD. Results showed that GonaCon provided relief from ACD by causing production of antibodies to GnRH, probably suppressing production and/or release of LH. Treatment caused many ACD symptoms to disappear, allowing the ferrets to return to a normal life. The study also found that the probability of developing ACD was significantly reduced in ferrets treated with GonaCon when young (1-3 years old) compared to untreated control animals. GonaCon caused injection site reaction in some animals when administered as an intramuscular injection but caused few side effects when administered subcutaneously. Both intramuscular and subcutaneous vaccination resulted in similar levels of GnRH antibody titers. Subcutaneous vaccination with GonaCon is thus recommended to prevent the onset of ACD and as a possible treatment for ACD-signs in domestic ferrets. Published

Vaccination against herpes zoster in developed countries

PubMed Central

Drolet, Mélanie; Oxman, Michael N.; Levin, Myron J.; Schmader, Kenneth E.; Johnson, Robert W.; Patrick, David; Mansi, James A.; Brisson, Marc

2013-01-01

Although progress has been made in the treatment of herpes zoster (HZ) and postherpetic neuralgia (PHN), available therapeutic options are only partially effective. Given evidence that a live-attenuated varicella-zoster-virus vaccine is effective at reducing the incidence of HZ, PHN and the burden of illness, policymakers and clinicians are being asked to make recommendations regarding the use of the zoster vaccine. In this report, we summarize the evidence regarding the: (1) burden of illness; (2) vaccine efficacy and safety; and (3) cost-effectiveness of vaccination, to assist evidence-based policy making and guide clinicians in their recommendations. First, there is general agreement that the overall burden of illness associated with HZ and PHN is substantial. Second, the safety and efficacy of the zoster vaccine at reducing the burden of illness due to HZ and the incidence of PHN have been clearly demonstrated in large placebo-controlled trials. However, uncertainty remains about the vaccine’s duration of protection. Third, vaccination against HZ is likely to be cost-effective when the vaccine is given at approximately 65 y of age, if vaccine duration is longer than 10 y. PMID:23324598

"The Impact of Mycobacterium tuberculosis Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" - Meeting report.

PubMed

Boggiano, Cesar; Eichelberg, Katrin; Ramachandra, Lakshmi; Shea, Jaqueline; Ramakrishnan, Lalita; Behar, Samuel; Ernst, Joel D; Porcelli, Steven A; Maeurer, Markus; Kornfeld, Hardy

2017-06-14

Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB. The workshop addressed early infection events, the impact of Mtb evolution on the development and maintenance of an adaptive immune response, and the factors that influence protection against and progression to active disease. Scientific gaps and areas of study to revitalize and accelerate TB vaccine design were discussed and prioritized. These included a comprehensive evaluation of innate and Mtb-specific adaptive immune responses in the lung at different stages of disease; determining the role of B cells and antibodies (Abs) during Mtb infection; development of better assays to measure Mtb burden following exposure, infection, during latency and after treatment, and approaches to improving current animal models to study Mtb immunogenicity, TB disease and transmission. Copyright © 2017.

Near-Infrared Laser Adjuvant for Influenza Vaccine

PubMed Central

Kashiwagi, Satoshi; Yuan, Jianping; Forbes, Benjamin; Hibert, Mathew L.; Lee, Eugene L. Q.; Whicher, Laura; Goudie, Calum; Yang, Yuan; Chen, Tao; Edelblute, Beth; Collette, Brian; Edington, Laurel; Trussler, James; Nezivar, Jean; Leblanc, Pierre; Bronson, Roderick; Tsukada, Kosuke; Suematsu, Makoto; Dover, Jeffrey; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C.

2013-01-01

Safe and effective immunologic adjuvants are often essential for vaccines. However, the choice of adjuvant for licensed vaccines is limited, especially for those that are administered intradermally. We show that non-tissue damaging, near-infrared (NIR) laser light given in short exposures to small areas of skin, without the use of additional chemical or biological agents, significantly increases immune responses to intradermal influenza vaccination without augmenting IgE. The NIR laser-adjuvanted vaccine confers increased protection in a murine influenza lethal challenge model as compared to unadjuvanted vaccine. We show that NIR laser treatment induces the expression of specific chemokines in the skin resulting in recruitment and activation of dendritic cells and is safe to use in both mice and humans. The NIR laser adjuvant technology provides a novel, safe, low-cost, simple-to-use, potentially broadly applicable and clinically feasible approach to enhancing vaccine efficacy as an alternative to chemical and biological adjuvants. PMID:24349390

Immunizing Cancer Patients: Which Patients? Which Vaccines? When to Give?

PubMed

Shah, Monika K; Kamboj, Mini

2018-05-15

Patients receiving treatment for cancer should be considered for age- and indication-appropriate vaccinations, and the responsibility for administration of these vaccines is shared between the oncologist and the primary care provider. Certain vaccine-preventable diseases have higher incidence rates among cancer patients and are associated with worse clinical outcomes. The Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices recommend certain vaccines for routine use in adults, including those with cancer. This article provides guidance to oncology clinicians on vaccine recommendations and safety of use in their patients.

Leishmaniasis in humans: drug or vaccine therapy?

PubMed Central

Ghorbani, Masoud; Farhoudi, Ramin

2018-01-01

Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death. People can carry some species of Leishmania for long periods without becoming ill, and symptoms depend on the form of the disease. There are many drugs and candidate vaccines available to treat leishmaniasis. For instance, antiparasitic drugs, such as amphotericin B (AmBisome), are a treatment of choice for leishmaniasis depending on the type of the disease. Despite the availability of different treatment approaches to treat leishmaniasis, therapeutic tools are not adequate to eradicate this infection. In the meantime, drug therapy has been limited because of adverse side effects and unsuccessful vaccine preparation. However, it can immediately make infections inactive. According to other studies, vaccination cannot eradicate leishmaniasis. There is no perfect vaccine or suitable drug to eradicate leishmaniasis completely. So far, no vaccine or drug has been provided to induce long-term protection and ensure effective immunity against leishmaniasis. Therefore, it is necessary that intensive research should be performed in drug and vaccine fields to achieve certain results. PMID:29317800

Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial.

PubMed

Kuyken, Willem; Hayes, Rachel; Barrett, Barbara; Byng, Richard; Dalgleish, Tim; Kessler, David; Lewis, Glyn; Watkins, Edward; Brejcha, Claire; Cardy, Jessica; Causley, Aaron; Cowderoy, Suzanne; Evans, Alison; Gradinger, Felix; Kaur, Surinder; Lanham, Paul; Morant, Nicola; Richards, Jonathan; Shah, Pooja; Sutton, Harry; Vicary, Rachael; Weaver, Alice; Wilks, Jenny; Williams, Matthew; Taylor, Rod S; Byford, Sarah

2015-07-04

Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence. Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months. In this single-blind, parallel, group randomised controlled trial (PREVENT), we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants, from primary care general practices in urban and rural settings in the UK. Participants were randomly assigned to either MBCT-TS or maintenance antidepressants (in a 1:1 ratio) with a computer-generated random number sequence with stratification by centre and symptomatic status. Participants were aware of treatment allocation and research assessors were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with patients followed up at five separate intervals during the 24-month study period. The primary analysis was based on the principle of intention to treat. The trial is registered with Current Controlled Trials, ISRCTN26666654. Between March 23, 2010, and Oct 21, 2011, we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practices. 212 patients were randomly assigned to MBCT-TS and 212 to maintenance antidepressants. The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months (hazard ratio 0·89, 95% CI 0·67-1·18

Vaccination and auto-immune rheumatic diseases: lessons learnt from the 2009 H1N1 influenza virus vaccination campaign.

PubMed

Touma, Zahi; Gladman, Dafna D; Urowitz, Murray B

2013-03-01

To determine the safety and efficacy of adjuvant and nonadjuvant influenza A/H1NI vaccination in patients with rheumatic diseases. Due to immune abnormalities and the use of steroids and immunosuppressant treatment, patients with rheumatic diseases are susceptible to infections including influenza. Infections continue to be one of the leading causes of morbidity and mortality in rheumatic diseases, partly due to the disease processes and partly due to medications. Viral infections are particularly an issue, so vaccinations would be advisable. However, because of the abnormalities in immune mechanisms in many rheumatic diseases, it is not clear whether vaccinations are well tolerated and effective. A number of studies confirmed the efficacy and safety of adjuvant and nonadjuvant influenza A/H1NI vaccination in patients with rheumatic diseases. The potential side effects associated with H1N1 vaccines were not different from those observed with seasonal influenza vaccine. The use of steroids and immunosuppressant therapies may alter the efficacy of the vaccines. Adjuvant and nonadjuvant influenza A/H1NI vaccinations have no clinically important effect on production or levels of autoantibodies in patients with rheumatic diseases. H1N1 vaccination should be given to patients with rheumatic diseases.

How Influenza Vaccination Policy May affect Vaccine Logistics

PubMed Central

Assi, Tina-Marie; Rookkapan, Korngamon; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T.; Welling, Joel S.; Norman, Bryan A.; Connor, Diana L.; Chen, Sheng-I; Slayton, Rachel B.; Laosiritaworn, Yongjua; Wateska, Angela R.; Wisniewski, Stephen R.; Lee, Bruce Y.

2012-01-01

Background When policymakers make decision about the target populations and timing of influenza vaccination, they may not consider the impact on the vaccine supply chains, which may in turn affect vaccine availability. Purpose Our goal is to explore the effects on the Thailand vaccine supply chain of introducing influenza vaccines and varying the target populations and immunization time-frames. Methods Utilized our custom-designed software HERMES (Highly Extensible Resource for Modeling Supply Chains), we developed a detailed, computational discrete-event simulation model of the Thailand's National Immunization Program (NIP) supply chain in Trang Province, Thailand., A suite of experiments simulated introducing influenza vaccines for different target populations and over different time-frames prior to and during the annual influenza season. Results Introducing influenza vaccines creates bottlenecks that reduce the availability of both influenza vaccines as well as the other NIP vaccines, with provincial to district transport capacity being the primary constraint. Even covering only 25% of the Advisory Committee on Immunization Practice-recommended population while administering the vaccine over six months hinders overall vaccine availability so that only 62% of arriving patients can receive vaccines. Increasing the target population from 25% to 100% progressively worsens these bottlenecks, while increasing influenza vaccination time - frame from 1 to 6 months decreases these bottlenecks. Conclusion Since the choice of target populations for influenza vaccination and the time-frame to deliver this vaccine can substantially affect the flow of all vaccines, policy-makers may want to consider supply chain effects when choosing target populations for a vaccine. PMID:22537993

Effectiveness of Antipsychotic Drugs for 24-Month Maintenance Treatment in First-Episode Schizophrenia: Evidence From a Community-Based "Real-World" Study.

PubMed

Zhang, Chen; Chen, Mei-Juan; Wu, Guo-Jun; Wang, Zuo-Wei; Rao, Shun-Zeng; Zhang, Yi; Yi, Zheng-Hui; Yang, Wei-Min; Gao, Ke-Ming; Song, Li-Sheng

2016-11-01

Maintenance treatment of schizophrenia with antipsychotic medications has become a standard for the prevention of psychotic relapse. However, little is known about the effectiveness of antipsychotic drugs for maintenance treatment in "real-world" populations with schizophrenia. We carried out a prospective study to assess the effectiveness of the most frequently prescribed antipsychotic drugs in the maintenance treatment of schizophrenia from 2 community settings. This study was conducted from October 2011 to December 2014. All participants were diagnosed with schizophrenia according to DSM-IV, were treated with an antipsychotic monotherapy, and were registered in a case management program with monthly monitoring for 24 months. The primary outcome measure, Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales were used to evaluate symptom severity and treatment response. The Personal and Social Performance scale (PSP) was used to evaluate the patients' social functioning. The Medication Adherence Rating Scale (MARS) was used to assess medication adherence behavior. On the basis of antipsychotic used at baseline, patients were clustered into 7 groups: aripiprazole (n = 21), clozapine (n = 84), chlorpromazine (n = 61), olanzapine (n = 34), perphenazine (n = 21), quetiapine (n = 27), and risperidone (n = 99). Of the 347 patients enrolled in the study, 312 completed the 24-month follow-up. There were no significant differences among the treatment groups in the PANSS total and subscale scores or the CGI-S and CGI-I scores over 24 months (all P values > .05). There were also no significant differences in interactions between PSP scores and antipsychotic drugs (P = .17). The remission rates increased as the follow-time lapsed in all groups, but no significant difference was observed in remission rates at each time point among the 7 groups (P values > .05). At the endpoint, MARS total

Correlates of human papillomavirus vaccination rates in low-income, minority adolescents: a multicenter study.

PubMed

Perkins, Rebecca B; Brogly, Susan B; Adams, William G; Freund, Karen M

2012-08-01

Low rates of human papillomavirus (HPV) vaccination in low-income, minority adolescents may exacerbate racial disparities in cervical cancer incidence. Using electronic medical record data and chart abstraction, we examined correlates of HPV vaccine series initiation and completion among 7702 low-income and minority adolescents aged 11-21 receiving primary care at one of seven medical centers between May 1, 2007, and June 30, 2009. Our population included 61% African Americans, 13% Caucasians, 15% Latinas, and 11% other races; 90% receive public insurance (e.g., Medicaid). We used logistic regression to estimate the associations between vaccine initiation and completion and age, race/ethnicity, number of contacts with the healthcare system, provider documentation, and clinical site of care. Of the 41% of adolescent girls who initiated HPV vaccination, 20% completed the series. A higher proportion of girls aged 11-<13 (46%) and 13-<18 (47%) initiated vaccination than those aged 18-21 (28%). In adjusted analyses, receipt of other recommended adolescent vaccines was associated with vaccine initiation, and increased contact with the medical system was associated with both initiation and completion of the series. Conversely, provider failure to document risky health behaviors predicted nonvaccination. Manual review of a subset of unvaccinated patients' charts revealed no documentation of vaccine discussions in 67% of cases. Fewer than half of low-income and minority adolescents receiving health maintenance services initiated HPV vaccination, and only 20% completed the series. Provider failure to discuss vaccination with their patients appears to be an important contributor to nonvaccination. Future research should focus on improving both initiation and completion of HPV vaccination in high-risk adolescents.

Keratitis in association with herpes zoster and varicella vaccines.

PubMed

Grillo, A P; Fraunfelder, F W

2017-07-01

The objective of this review was to collect reports of keratitis in association with herpes zoster virus (HZV) or varicella zoster virus (VZV) vaccines. HZV vaccination is intended for at-risk adult populations and VZV vaccination is intended for all pediatric patients. We reviewed the literature and reports of keratitis in association with herpes zoster or varicella vaccine from the National Registry of Drug-Induced Ocular Side Effects and the World Health Organization. Twenty-four cases of unilateral keratitis in association with VZV vaccines were collected from the adverse reaction databases and literature. In most cases, the onset of keratitis occurred within days of vaccination and resolved with topical steroid eye drops and oral acyclovir. Data suggest that keratitis in association with herpes zoster or varicella vaccine is rare, is usually self-limited or resolves with treatment. The mechanism may be the persistence of viral antigens in the cornea after VZV vaccination or herpes zoster ophthalmicus. This reaction is probable, given the plausible biological mechanism, the temporal relationship between vaccination and keratitis, and overall patterns of presentation after vaccination. Copyright 2017 Clarivate Analytics.

Vaccine-preventable diseases, vaccines and Guillain-Barre' syndrome.

PubMed

Principi, Nicola; Esposito, Susanna

2018-06-04

Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy. Infections and vaccines have been hypothesized to play a role in triggering GBS development. These beliefs can play a role in reducing vaccination coverage. In this report, data concerning this hypothesis are discussed. It is shown that an association between vaccine administration and GBS has never been proven for most of debated vaccines, although it cannot be definitively excluded. The only exception is the influenza vaccine, at least for the preparation used in 1976. For some vaccines, such as measles/mumps/rubella, human papillomavirus, tetravalent conjugated meningococcal vaccine, and influenza, the debate between supporters and opponents of vaccination remains robust and perception of vaccines' low safety remains a barrier to achieving adequate vaccination coverage. Less than 1 case of GBS per million immunized persons might occur for these vaccines. However, in some casesimmunization actually reduces the risk of GBS development. In addition, the benefits of vaccination are clearly demonstrated by the eradication or enormous decline in the incidence of many vaccine-preventable diseases. These data highlight that the hypothesized risks of adverse events, such as GBS, cannot be considered a valid reason to avoid the administration of currently recommended vaccines. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anticipatory reward processing among cocaine-dependent individuals with and without concurrent methadone-maintenance treatment: Relationship to treatment response*

PubMed Central

Yip, Sarah W.; DeVito, Elise E.; Kober, Hedy; Worhunsky, Patrick D.; Carroll, Kathleen M.; Potenza, Marc N.

2016-01-01

Background Cocaine dependence among opioid-dependent methadone-maintained individuals is a significant public health problem and is particularly challenging to treat. The neurobiology of this clinically complex population has not been previously assessed using fMRI. Methods fMRI data from cocaine-dependent, methadone-maintained (CD-MM) patients (n=24), cocaine-dependent (CD) patients (n=20) and healthy comparison (HC; n=21) participants were acquired during monetary incentive delay task performance. All patients were scanned prior to treatment for cocaine dependence. Between-group differences in anticipatory reward and loss processing were assessed using whole-brain ANOVAs in SPM12 (pFWE<.05). Correlations between durations of abstinence during treatment and BOLD responses within the insula and caudate were also explored. Results Main effects of diagnostic group, primarily involving decreased BOLD responses among CD-MM patients in comparison to HCs, were observed during anticipatory reward and loss processing within regions of posterior cingulate cortex, precuneus, inferior frontal gyrus and dorsolateral prefrontal cortex. BOLD responses within the right caudate were negatively associated with percentage of cocaine-negative urines during treatment among CD-MM patients, but not among non-methadone-maintained CD patients. Conclusions These data suggest neurofunctional differences that may be related to treatment outcomes for behavioral therapies between cocaine-dependent individuals with and without methadone-maintenance treatment. These findings may relate to differences in treatment efficacies and to the elevated relapse rates observed in methadone-maintained populations. PMID:27430401

[Current situation on new psychoactive substances abuse among methadone maintenance treatment patients in China].

PubMed

Cheng, Z; Dai, M M; Cao, X B

2018-04-10

Methadone maintenance treatment (MMT) greatly contributed to the successful outcomes of prevention and control on both AIDS and drug abuse in China. However, the features on drug abuse changed in the past decades, and the prevalence of new psychoactive substances abuse potentially somehow offset the achievement of MMT. This paper concised the information on research and surveys of this issue that targeting on the current situation, characteristics, related factors and relevant public health problem on new psychoactive substances abuse, among patients who have been on MMT, in China.

Dendritic cell based vaccines: progress in immunotherapy studies for prostate cancer.

PubMed

Ragde, Haakon; Cavanagh, William A; Tjoa, Benjamin A

2004-12-01

No effective treatment is currently available for metastatic prostate cancer. Dendritic cell (DC) based cancer vaccine research has emerged from the laboratories to human clinical trials. We describe progress in the development of DC based prostate cancer vaccine. The literature was reviewed for major contributions to a growing number of studies that demonstrate the potential of DC based immunotherapeutics for prostate cancer. Background topics relating to DC based immunotherapy theory and practice are also addressed. DCs have been recognized as the most efficient antigen presenting cells that have the capacity to initiate naive T cell response in vitro and in vivo. During their differentiation and maturation pathways, dendritic cells can efficiently capture, process and present antigens for T cell activation. These characteristics make DC an attractive choice as the cellular adjuvant for cancer vaccines. Advances in DC generation, loading, and maturation methodologies have made it possible to generate clinical grade vaccines for various human trials. More than 100 DC vaccine trials, including 7 studies of patients with advanced prostate cancer have been reported to date. These vaccines were generally well tolerated with no significant adverse toxicity reported. Clinical responders have been identified in these studies. The new prospects opened by DC based vaccines for prostate cancer are fascinating. When compared to conventional treatments, DC vaccinations have few side effects. Improvements in patient selection, vaccine delivery strategies, immune monitoring and vaccine manufacturing will be crucial in moving DC based prostate cancer vaccines closer to the clinics.

Formalin-inactivated Venezuelan Equine Encephalomyelitis (Trinidad Strain) Vaccine Produced in Rolling-Bottle Cultures of Chicken Embryo Cells

PubMed Central

Cole, Francis E.; May, Stephen W.; Robinson, David M.

1973-01-01

Formalin-inactivated Venezuelan equine encephalomyelitis vaccine was prepared from virus grown in rolling-bottle cultures of chicken embryo cells. Trinidad strain virus was propagated in these cultures with a maintenance medium consisting of serum-free medium 199 containing 0.25% human serum albumin (USP) and antibiotics. Manipulation of multiplicity of inoculum (0.06 to 0.00006) and maintenance medium volume (100 to 300 ml) resulted in high-titered virus yields and only moderate cell destruction when fluids from infected cultures were harvested at 18 to 24 hr. The virus was inactivated at 37 C by 0.05% Formalin within 8 to 10 hr and with 0.1% Formalin within 6 to 8 hr. Single dose, antigen extinction tests in mice performed with 30 small-scale vaccine lots showed excellent potency at either Formalin concentration with inactivation periods ranging from 24 to 96 hr. PMID:4694345

Marker vaccine strategies and candidate CSFV marker vaccines.

PubMed

Dong, Xiao-Nan; Chen, Ying-Hua

2007-01-04

Classical swine fever (CSF) is an economically important highly contagious disease of swine worldwide. Classical swine fever virus (CSFV) is its etiological agent, and the only natural hosts are domestic pigs and wild boars. Although field CSFV strains vary in the virulence, they all result in serious losses in pig industry. Highly virulent field strains generally cause acute disease and high mortality; moderately virulent field strains raise subacute or chronic infections; postnatal infection by low virulent field strains produces subclinical infection and mortality in the new-born piglets. CSFV can cross the placental barrier, and this transplacental transmission usually results in mortality of fetuses and birth of congenitally infected pigs with a late-onset disease and death. Two main strategies to control CSF epidemic are systematic prophylactic vaccination with live attenuated vaccines (such as C-strain) and non-vaccination stamping-out policy. But neither of them is satisfying enough. Marker vaccine and companion serological diagnostic test is thought to be a promising strategy for future control and eradication of CSF. During the past 15 years, various candidate marker vaccines were constructed and evaluated in the animal experiments, including recombinant chimeric vaccines, recombinant deletion vaccines, DNA vaccines, subunit vaccines and peptide vaccines. Among them, two subunit vaccines entered the large scale marker vaccine trial of EU in 1999. Although they failed to fulfil all the demands of the Scientific Veterinary Committee, they successfully induced solid immunity against CSFV in the vaccinated pigs. It can be expected that new potent marker vaccines might be commercially available and used in systematic prophylactic vaccination campaign or emergency vaccination in the next 15 years. Here, we summarized current strategies and candidate CSFV marker vaccines. These strategies and methods are also helpful for the development of new

Vaccines, adjuvants and autoimmunity.

PubMed

Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

2015-10-01

Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study

PubMed Central

Ivers, Louise C; Hilaire, Isabelle J; Teng, Jessica E; Almazor, Charles P; Jerome, J Gregory; Ternier, Ralph; Boncy, Jacques; Buteau, Josiane; Murray, Megan B; Harris, Jason B; Franke, Molly F

2015-01-01

Background Between April and June 2012, a reactive cholera vaccination campaign was conducted in Haiti using an oral inactivated bivalent whole-cell vaccine (BivWC). Methods We conducted a case-control study to estimate field effectiveness of the vaccine. Cases had acute watery diarrhea, sought treatment at one of three participating cholera treatment units from October 24, 2012 through March 9, 2014, and had a stool sample positive for cholera by culture. For each case, four controls (individuals who did not seek treatment for acute watery diarrhea) were matched by location of residence, calendar time, and age. We also conducted a bias-indicator case-control study to assess the likelihood of bias in the vaccine effectiveness (VE) study. Findings During the study period, 114 eligible individuals presented with acute watery diarrhea and were enrolled. 47 were analyzed as cases in the VE case-control study and 42 as cases in the bias-indicator study. In multivariable analyses, VE was 63% [95% confidence interval (CI): 8%–85%] by self-reported vaccination and 58% [95% CI: 13%–80%] for verified vaccination. Neither self-reported nor verified vaccination was significantly associated with non-cholera diarrhea (VE: 18% [95% CI: −208%–−78%] by self-report and −21% [95%CI: −238%–57%] for verified vaccination). Interpretation BivWC oral cholera vaccine was effective in protecting against cholera in Haiti during the study period –from 4 through 24 months after vaccination. Vaccination is an important component of epidemic cholera control efforts. Funding National Institutes of Health, Delivering Oral Vaccines Effectively project, Department of Global Health and Social Medicine at Harvard Medical School. PMID:25701994

Antibody response to an anti-rabies vaccine in a dog population under field conditions in Bolivia.

PubMed

Suzuki, K; González, E T; Ascarrunz, G; Loza, A; Pérez, M; Ruiz, G; Rojas, L; Mancilla, K; Pereira, J A C; Guzman, J A; Pecoraro, M R

2008-10-01

Rabies remains an important public health issue in Bolivia, South America. Public concern and fears are most focussed on dogs as the source of rabies. The objective of the present study was to assess immunity of an inactivated suckling mouse brain vaccine against canine rabies used for the official vaccination campaigns under field conditions in an endemic area of rabies in Bolivia. A total of 236 vaccinated and 44 unvaccinated dogs in Santa Cruz de la Sierra, selected using stratified random sampling, were investigated in order to obtain owned dog characteristics and antibody titres against rabies in April 2007. The proportion of vaccinated dogs with an antibody titre exceeded the protection threshold value of 0.5 EU/ml was 58% [95% confidence intervals (CI): 52-65], indicating that vaccination is likely to elicit an antibody response (odds ratio 6.3, 95% CI: 1.2-11.5). The range of geometric mean of antibody titre for vaccinated dogs (0.89 EU/ml; 95% CI: 0.75-1.04) was considered to meet the minimal acceptable level indicating an adequate immune response to the vaccine. However, the titre level was not satisfactory in comparison with the results from other field investigations with inactivated tissue culture vaccines. It is recommended for public health authorities to (1) consider modernizing their vaccine manufacturing method because the level of immunity induced by the current vaccine is comparably low, (2) conduct frequent vaccination campaigns to maintain high levels of vaccination coverage, and (3) actively manage the domestic dog population in the study area, which is largely responsible for rabies maintenance.

Vaccine hesitancy

PubMed Central

Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

2013-01-01

Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

Managed Care’s Dual Impact on Outpatient Substance Abuse Treatment: Methadone Maintenance vs. Drug Free

PubMed Central

Sindelar, Jody L.; Olmstead, Todd A.

2013-01-01

The number and type of services offered at substance abuse treatment (SAT) facilities are important aspects of the quality of care. Managed care (MC) is a growing presence in SAT and has been shown to affect the provision of treatment. We expand on earlier work and examine the impact of managed care on the number and type of services offered by methadone maintenance (MM) and drug-free (DF) outpatient treatment facilities. We use the econometric technique of instrumental variables to address the issue of endogeneity of MC and service offerings, thereby allowing a causal interpretation of results. Using data from the 2000 National Survey of Substance Abuse Treatment Services, we find that MC significantly increases the total number of services offered in MM outpatient facilities by four, yet decreases the number by two in DF outpatient facilities. We also show how the impact on specific services differs by modality and provide explanations for our findings. PMID:24062595

Metazoan Parasite Vaccines: Present Status and Future Prospects

PubMed Central

Stutzer, Christian; Richards, Sabine A.; Ferreira, Mariette; Baron, Samantha; Maritz-Olivier, Christine

2018-01-01

Eukaryotic parasites and pathogens continue to cause some of the most detrimental and difficult to treat diseases (or disease states) in both humans and animals, while also continuously expanding into non-endemic countries. Combined with the ever growing number of reports on drug-resistance and the lack of effective treatment programs for many metazoan diseases, the impact that these organisms will have on quality of life remain a global challenge. Vaccination as an effective prophylactic treatment has been demonstrated for well over 200 years for bacterial and viral diseases. From the earliest variolation procedures to the cutting edge technologies employed today, many protective preparations have been successfully developed for use in both medical and veterinary applications. In spite of the successes of these applications in the discovery of subunit vaccines against prokaryotic pathogens, not many targets have been successfully developed into vaccines directed against metazoan parasites. With the current increase in -omics technologies and metadata for eukaryotic parasites, target discovery for vaccine development can be expedited. However, a good understanding of the host/vector/pathogen interface is needed to understand the underlying biological, biochemical and immunological components that will confer a protective response in the host animal. Therefore, systems biology is rapidly coming of age in the pursuit of effective parasite vaccines. Despite the difficulties, a number of approaches have been developed and applied to parasitic helminths and arthropods. This review will focus on key aspects of vaccine development that require attention in the battle against these metazoan parasites, as well as successes in the field of vaccine development for helminthiases and ectoparasites. Lastly, we propose future direction of applying successes in pursuit of next generation vaccines. PMID:29594064

For whom does it work? moderators of outcome on the effect of a transdiagnostic internet-based maintenance treatment after inpatient psychotherapy: randomized controlled trial.

PubMed

Ebert, David Daniel; Gollwitzer, Mario; Riper, Heleen; Cuijpers, Pim; Baumeister, Harald; Berking, Matthias

2013-10-10

Recent studies provide evidence for the effectiveness of Internet-based maintenance treatments for mental disorders. However, it is still unclear which participants might or might not profit from this particular kind of treatment delivery. The study aimed to identify moderators of treatment outcome in a transdiagnostic Internet-based maintenance treatment (TIMT) offered to patients after inpatient psychotherapy for mental disorders in routine care. Using data from a randomized controlled trial (N=400) designed to test the effectiveness of TIMT, we performed secondary analyses to identify factors moderating the effects of TIMT (intervention) when compared with those of a treatment-as-usual control condition. TIMT involved an online self-management module, asynchronous patient-therapist communication, a peer support group, and online-based progress monitoring. Participants in the control condition had unstructured access to outpatient psychotherapy, standardized outpatient face-to-face continuation treatment, and psychotropic management. Self-reports of psychopathological symptoms and potential moderators were assessed at the start of inpatient treatment (T1), at discharge from inpatient treatment/start of TIMT (T2), and at 3-month (T3) and 12-month follow-up (T4). Education level, positive outcome expectations, and diagnoses significantly moderated intervention versus control differences regarding changes in outcomes between T2 and T3. Only education level moderated change differences between T2 and T4. The effectiveness of the intervention (vs control) was more pronounced among participants with a low (vs high) education level (T2-T3: B=-0.32, SE 0.16, P=.049; T2-T4: B=-0.42, SE 0.21, P=.049), participants with high (vs low) positive outcome expectations (T2-T3: B=-0.12, SE 0.05, P=.02) and participants with anxiety disorder (vs mood disorder) (T2-T3: B=-0.43, SE 0.21, P=.04). Simple slope analyses revealed that despite some subgroups benefiting less from the

Intravenous immunoglobulin for maintenance treatment of chronic inflammatory demyelinating polyneuropathy: a multicentre, open-label, 52-week phase III trial

PubMed Central

Mori, Masahiro; Misawa, Sonoko; Suzuki, Miki; Nishiyama, Kazutoshi; Mutoh, Tatsuro; Doi, Shizuki; Kokubun, Norito; Kamijo, Mikiko; Yoshikawa, Hiroo; Abe, Koji; Nishida, Yoshihiko; Okada, Kazumasa; Sekiguchi, Kenji; Sakamoto, Ko; Kusunoki, Susumu; Sobue, Gen; Kaji, Ryuji

2017-01-01

Objective Short-term efficacy of induction therapy with intravenous immunoglobulin (Ig) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is well established. However, data of previous studies on maintenance therapy were limited up to 24-week treatment period. We aimed to investigate the efficacy and safety of longer-term intravenous Ig therapy for 52 weeks. Methods This study was an open-label phase 3 clinical trial conducted in 49 Japanese tertiary centres. 49 patients with CIDP who fulfilled diagnostic criteria were included. After an induction intravenous Ig therapy (0.4 g/kg/day for five consecutive days), maintenance dose intravenous Ig (1.0 g/kg) was given every 3 weeks for up to 52 weeks. The primary outcome measures were the responder rate at week 28 and relapse rate at week 52. The response and relapse were defined with the adjusted Inflammatory Neuropathy Cause and Treatment scale. Results At week 28, the responder rate was 77.6% (38/49 patients; 95% CI 63% to 88%), and the 38 responders continued the maintenance therapy. At week 52, 4 of the 38 (10.5%) had a relapse (95% CI 3% to 25%). During 52 weeks, 34 (69.4%) of the 49 enrolled patients had a maintained improvement. Adverse events were reported in 94% of the patients; two patients (66-year-old and 76-year-old men with hypertension or diabetes) developed cerebral infarction (lacunar infarct with good recovery), and the other adverse effects were mild and resolved by the end of the study period. Conclusions Maintenance treatment with 1.0 g/kg intravenous Ig every 3 weeks is an efficacious therapy for patients with CIDP, and approximately 70% of them had a sustained remission for 52 weeks. Thrombotic complications should be carefully monitored, particularly in elderly patients with vascular risk factors. Trial registration number ClinicalTrials.gov (NCT01824251). PMID:28768822

Intravenous immunoglobulin for maintenance treatment of chronic inflammatory demyelinating polyneuropathy: a multicentre, open-label, 52-week phase III trial.

PubMed

Kuwabara, Satoshi; Mori, Masahiro; Misawa, Sonoko; Suzuki, Miki; Nishiyama, Kazutoshi; Mutoh, Tatsuro; Doi, Shizuki; Kokubun, Norito; Kamijo, Mikiko; Yoshikawa, Hiroo; Abe, Koji; Nishida, Yoshihiko; Okada, Kazumasa; Sekiguchi, Kenji; Sakamoto, Ko; Kusunoki, Susumu; Sobue, Gen; Kaji, Ryuji

2017-10-01

Short-term efficacy of induction therapy with intravenous immunoglobulin (Ig) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is well established. However, data of previous studies on maintenance therapy were limited up to 24-week treatment period. We aimed to investigate the efficacy and safety of longer-term intravenous Ig therapy for 52 weeks. This study was an open-label phase 3 clinical trial conducted in 49 Japanese tertiary centres. 49 patients with CIDP who fulfilled diagnostic criteria were included. After an induction intravenous Ig therapy (0.4 g/kg/day for five consecutive days), maintenance dose intravenous Ig (1.0 g/kg) was given every 3 weeks for up to 52 weeks. The primary outcome measures were the responder rate at week 28 and relapse rate at week 52. The response and relapse were defined with the adjusted Inflammatory Neuropathy Cause and Treatment scale. At week 28, the responder rate was 77.6% (38/49 patients; 95% CI 63% to 88%), and the 38 responders continued the maintenance therapy. At week 52, 4 of the 38 (10.5%) had a relapse (95% CI 3% to 25%). During 52 weeks, 34 (69.4%) of the 49 enrolled patients had a maintained improvement. Adverse events were reported in 94% of the patients; two patients (66-year-old and 76-year-old men with hypertension or diabetes) developed cerebral infarction (lacunar infarct with good recovery), and the other adverse effects were mild and resolved by the end of the study period. Maintenance treatment with 1.0 g/kg intravenous Ig every 3 weeks is an efficacious therapy for patients with CIDP, and approximately 70% of them had a sustained remission for 52 weeks. Thrombotic complications should be carefully monitored, particularly in elderly patients with vascular risk factors. ClinicalTrials.gov (NCT01824251). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise

The tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic with a clinically acceptable safety profile in subjects previously vaccinated with a tetravalent polysaccharide vaccine.

PubMed

Dbaibo, Ghassan; Van der Wielen, Marie; Reda, Mariam; Medlej, Fouad; Tabet, Carelle; Boutriau, Dominique; Sumbul, Anne; Anis, Sameh; Miller, Jacqueline M

2012-08-01

The immunogenicity and safety of the tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in subjects previously vaccinated with a tetravalent meningococcal polysaccharide vaccine and in subjects without previous meningococcal vaccination. In this phase II, open, controlled study (NCT00661557), healthy subjects aged 4.5-34 years received one dose of MenACWY-TT at month 0. Subjects in the MPS group (n=192) had received polysaccharide vaccine in a study conducted 30-42 months earlier; age-matched subjects in the noMPS control group (n=79) had received no meningococcal vaccination within the past 10 years. Serum bactericidal activity using rabbit complement (rSBA) was measured at month 0 and month 1. At month 1, ≥97.0% of subjects had rSBA titers ≥1:128. Post-vaccination rSBA geometric mean titers (GMTs) were ≥3.9-fold higher than pre-vaccination in both treatment groups. Exploratory analyses showed no statistically significant differences between groups in percentages of subjects with rSBA titers ≥1:8 and ≥1:128, but significantly lower rSBA GMTs and vaccine response rates for each serogroup in the MPS versus the noMPS group. MenACWY-TT had an acceptable safety profile in both groups. These results suggest that MenACWY-TT could be used in vaccination programs irrespective of the pre-vaccination status with polysaccharide vaccine. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Safety and immunogenicity of a single intramuscular dose of a tetanus-diphtheria toxoid (Td) vaccine (BR-TD-1001) in healthy Korean adult subjects.

PubMed

Hong, Taegon; Chung, Yong-Ju; Kim, Tae-Yeon; Kim, Ik-Hwan; Choe, Yong-Kyung; Lee, Jongtae; Jeon, Sangil; Han, Seunghoon; Yim, Dong-Seok

2015-01-01

BR-TD-1001 was developed as a booster for the immunity maintenance of diphtheria and tetanus. The aim of this study was to evaluate the safety and immunogenicity of BR-TD-1001 (test vaccine) in comparison with placebo and an active comparator in healthy Korean adults. A randomized, double-blind, placebo-controlled, active comparator, phase I clinical trial was conducted. Fifty subjects were randomly assigned to one of 3 treatment groups in a ratio of 2:2:1, and were administered a single intramuscular dose of test vaccine, active comparator, or placebo, respectively. All subjects were monitored for 4 weeks after injection. The antibody titers of the patients 2 and 4 weeks after vaccination were compared with the baseline. The frequencies of all adverse events including adverse drug reactions in the test group were not statistically different from those of the other treatment groups (P = 0.4974, 0.3061). No serious adverse event occurred, and no subject was withdrawn from the study for safety. The seroprotection rates against both tetanus and diphtheria at 4 weeks after vaccination were over 0.95. For anti-tetanus antibody, the geometric mean titer in the test group was significantly higher than those of the other groups (P = 0.0364, 0.0033). The geometric mean titer of anti-diphtheria antibody in the test group was significantly higher than the value of the placebo (P = 0.0347) while it was not for the value of the active comparator (P = 0.8484). In conclusion, BR-TD-1001 was safe, well-tolerated, and showed sufficient immunogenicity as a booster for diphtheria and tetanus.

Vaccines.gov

MedlinePlus

... Vaccine Safety Vaccines Work Vaccine Types Vaccine Ingredients Vaccines by Disease Chickenpox ... Typhoid Fever Whooping Cough (Pertussis) Yellow Fever Who and When Infants, Children, and Teens ...

Effects of live and killed vaccines against Mycoplasma gallisepticum on the performance characteristics of commercial layer chickens.

PubMed

Jacob, R; Branton, S L; Evans, J D; Leigh, S A; Peebles, E D

2014-06-01

Different vaccine strains of Mycoplasma gallisepticum have been used on multiple-age commercial layer farms in an effort to protect birds against virulent field-strain infections. Use of the F-strain of M. gallisepticum (FMG), as an overlay vaccine during lay, may be necessary because of the lower level of protection afforded by M. gallisepticum vaccines of low virulence given before lay. Two replicate trials were conducted to investigate effects of live and killed M. gallisepticum vaccines administered individually and in combination before lay, in conjunction with an FMG vaccine overlay after peak egg production (EP), on the performance characteristics of commercial layers. The following treatments were utilized at 10 wk of age (woa): 1) control (no vaccinations); 2) ts11 strain M. gallisepticum (ts11MG) vaccine; 3) M. gallisepticum-Bacterin vaccine (MG-Bacterin); and 4) ts11MG and MG-Bacterin vaccines combination. At 45 woa, half of the birds were overlaid with an FMG vaccine. Hen mortality, BW, egg weight, percentage hen-day EP, egg blood spots, and egg meat spots were determined at various time periods between 18 and 52 woa. The data from each trial were pooled. Treatment did not affect performance in interval I (23 to 45 woa). However, during interval II (46 to 52 woa), the EP of control and MG-Bacterin-vaccinated birds that later received an FMG vaccine overlay was lower than that in the other treatment groups. Furthermore, treatment application reduced bird BW during interval II. Despite the effects on BW and EP, no differences were observed for egg blood or meat spots among the various treatments. It is suggested that the vaccination of commercial layers before lay with ts11MG, but not MG-Bacterin, may reduce the negative impacts of an FMG overlay vaccination given during lay. These results establish that the vaccination of pullets with ts11MG in combination with the vaccination of hens with an FMG overlay, for continual protection against field-strain M

A brief history of vaccines & vaccination in India.

PubMed

Lahariya, Chandrakant

2014-04-01

The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.

A brief history of vaccines & vaccination in India

PubMed Central

Lahariya, Chandrakant

2014-01-01

The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts. PMID:24927336