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Sample records for single vaccine dose

  1. Vaxchora: A Single-Dose Oral Cholera Vaccine.

    Science.gov (United States)

    Cabrera, Adriana; Lepage, Jayne E; Sullivan, Karyn M; Seed, Sheila M

    2017-07-01

    To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

  2. Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

    Science.gov (United States)

    Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

    2018-02-01

    To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

  3. Assessment of coverage levels of single dose measles vaccine

    International Nuclear Information System (INIS)

    Tariq, P.

    2003-01-01

    Objective: To study the consequences of low coverage levels of a single dose of measles vaccine. Results: mean age observed in measles cases was 2 years and 8 months with a range from 3 months to 8 years. Maximum number of cases reported were <1 year of age (n=22,32%). Fifty percent of cases were seen among vaccinated children. Seventy-five percent (n=51) had history of contact with a measles case. Pneumonia was the commonest complication followed by acute gastroenteritis, encephalitis, febrile convulsions, oral ulcers, oral thrush, eye changes of vitamin-A deficiency and pulmonary tuberculosis (T.B.) in descending order of frequency. Fifty four cases were successfully treated for complications of measles and discharged. Nine cases left against medical advice. Five patients died all of them had encephalitis either alone (n=1) or in combination with pneumonia and acute gastroenteritis (n=4). Conclusion: There is a dire need to increase the immunization coverage to reduce the rate of vaccine failure and achieve effective control of measles.(author)

  4. Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge

    CSIR Research Space (South Africa)

    Mallajosyula, JK

    2014-03-01

    Full Text Available 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H 1 N 1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large...

  5. Bluetongue Disabled Infectious Single Animal (DISA) vaccine: Studies on the optimal route and dose in sheep.

    Science.gov (United States)

    van Rijn, Piet A; Daus, Franz J; Maris-Veldhuis, Mieke A; Feenstra, Femke; van Gennip, René G P

    2017-01-05

    Bluetongue (BT) is a disease of ruminants caused by bluetongue virus (BTV) transmitted by biting midges of the Culicoides genus. Outbreaks have been controlled successfully by vaccination, however, currently available BT vaccines have several shortcomings. Recently, we have developed BT Disabled Infectious Single Animal (DISA) vaccines based on live-attenuated BTV without expression of dispensable non-structural NS3/NS3a protein. DISA vaccines are non-pathogenic replicating vaccines, do not cause viremia, enable DIVA and are highly protective. NS3/NS3a protein is involved in virus release, cytopathogenic effect and suppression of Interferon-I induction, suggesting that the vaccination route can be of importance. A standardized dose of DISA vaccine for serotype 8 has successfully been tested by subcutaneous vaccination. We show that 10 and 100times dilutions of this previously tested dose did not reduce the VP7 humoral response. Further, the vaccination route of DISA vaccine strongly determined the induction of VP7 directed antibodies (Abs). Intravenous vaccination induced high and prolonged humoral response but is not practical in field situations. VP7 seroconversion was stronger by intramuscular vaccination than by subcutaneous vaccination. For both vaccination routes and for two different DISA vaccine backbones, IgM Abs were rapidly induced but declined after 14days post vaccination (dpv), whereas the IgG response was slower. Interestingly, intramuscular vaccination resulted in an initial peak followed by a decline up to 21dpv and then increased again. This second increase is a steady and continuous increase of IgG Abs. These results indicate that intramuscular vaccination is the optimal route. The protective dose of DISA vaccine has not been determined yet, but it is expected to be significantly lower than of currently used BT vaccines. Therefore, in addition to the advantages of improved safety and DIVA compatibility, the novel DISA vaccines will be cost

  6. Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine

    Science.gov (United States)

    Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.

    2012-01-01

    Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic anti-tumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589

  7. Successful comeback of the single-dose live oral cholera vaccine CVD 103-HgR.

    Science.gov (United States)

    Herzog, Christian

    2016-01-01

    Effective and easy to administer cholera vaccines are in need more than ever, for at risk populations and travellers alike. In many parts of the world cholera is still endemic, causing outbreaks and constituting repeatedly serious public health problems. The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo. However, there were strong headwinds: In the 1990s the indication for cholera vaccines was generally downplayed by experts and in 1997 the European Commission called for a moratorium of GMOs which blocked the registration in the European Union. Thus, demand for this vaccine remained low and in 2003 it was taken off the market for economic reasons. After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). What had happened? This commentary gives a critical account of an almost unbelievable string of misadventures, emerging adverse circumstances and man-made failures which nearly killed this single-dose live oral cholera vaccine. The good news is that patience and persistence lead to success in the end, allowing good science to prevail for the benefit of those in need. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage.

    Science.gov (United States)

    Shan, Chao; Muruato, Antonio E; Jagger, Brett W; Richner, Justin; Nunes, Bruno T D; Medeiros, Daniele B A; Xie, Xuping; Nunes, Jannyce G C; Morabito, Kaitlyn M; Kong, Wing-Pui; Pierson, Theodore C; Barrett, Alan D; Weaver, Scott C; Rossi, Shannan L; Vasconcelos, Pedro F C; Graham, Barney S; Diamond, Michael S; Shi, Pei-Yong

    2017-09-22

    Zika virus infection during pregnancy can cause congenital abnormities or fetal demise. The persistence of Zika virus in the male reproductive system poses a risk of sexual transmission. Here we demonstrate that live-attenuated Zika virus vaccine candidates containing deletions in the 3' untranslated region of the Zika virus genome (ZIKV-3'UTR-LAV) prevent viral transmission during pregnancy and testis damage in mice, as well as infection of nonhuman primates. After a single-dose vaccination, pregnant mice challenged with Zika virus at embryonic day 6 and evaluated at embryonic day 13 show markedly diminished levels of viral RNA in maternal, placental, and fetal tissues. Vaccinated male mice challenged with Zika virus were protected against testis infection, injury, and oligospermia. A single immunization of rhesus macaques elicited a rapid and robust antibody response, conferring complete protection upon challenge. Furthermore, the ZIKV-3'UTR-LAV vaccine candidates have a desirable safety profile. These results suggest that further development of ZIKV-3'UTR-LAV is warranted for humans.Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.

  9. Is a single dose of meningococcal serogroup C conjugate vaccine sufficient for protection? experience from the Netherlands

    Directory of Open Access Journals (Sweden)

    Kaaijk Patricia

    2012-02-01

    Full Text Available Abstract Background The first meningococcal serogroup C (MenC conjugate vaccine was licensed in 1999 and introduced in the United Kingdom. Countries that have implemented the MenC vaccine since then in their national immunisation programmes use different schedules. Nevertheless, all involved countries seem to experience substantial declines in the incidence of MenC disease. Discussion Since 2001, the MenC conjugate vaccine has been implemented in the Netherlands by offering a single dose to all children aged 14 months. Prior to the introduction of the vaccine into the national immunisation programme, a catch-up vaccination campaign was initiated in which a single dose of the MenC conjugate vaccine was offered to all children aged from 14 months up to and including 18 years. Since then, there has been no report of any case of MenC disease among immunocompetent vaccinees. Administration of a single dose of MenC conjugate vaccine after infancy could be beneficial considering the already complex immunisation schedules with large numbers of vaccinations in the first year of life. The present paper deals with the advantages and critical aspects of a single dose of the MenC conjugate vaccine. Summary A single dose of MenC conjugate vaccine at the age of 14 months in combination with a catch up vaccine campaign appeared to be a successful strategy to prevent MenC disease in the Netherlands, thereby confirming that a single dose of the vaccine could sufficiently protect against disease. Nevertheless, this approach can only be justified in countries with a relatively low incidence of serogroup C meningococcal disease in the first year of life. Furthermore, a good surveillance programme is recommended for timely detection of vaccine breakthroughs and outbreaks among non-vaccinees, since long-term protection after a single dose in the second year of life cannot currently be guaranteed.

  10. Comparison of immune persistence among inactivated and live attenuated hepatitis a vaccines 2 years after a single dose

    Science.gov (United States)

    Zhang, Xiaoshu; An, Jing; Tu, Aixia; Liang, Xuefeng; Cui, Fuqiang; Zheng, Hui; Tang, Yu; Liu, Jianfeng; Wang, Xuxia; Zhang, Ningjing; Li, Hui

    2016-01-01

    ABSTRACT Objective: Compare immune persistence from one dose of each of 3 different hepatitis A vaccines when given to school-age children: a domestic, live attenuated hepatitis A vaccine (H2 vaccine); a domestic inactivated hepatitis A vaccine (Healive®); and an imported, inactivated hepatitis A vaccine (Havrix®),.Methods: School-age children were randomized into 1 of 4 groups to receive a single dose of a vaccine: H2 vaccine, Healive®, Havrix®, or hepatitis B vaccine [control]. Serum samples were collected 12 and 24 months after vaccination for measurement of anti-HAV IgG using microparticle enzyme immunoassay. Seropositivity was defined as ≥ 20 mUI/ml. We compared groups on seropositivity and geometric mean concentration (GMC). Results: Seropositive rates for the H2, Healive®, Havrix®, and control groups were 64%, 94.4%, 73%, and 1.0%, respectively, 12-months post-vaccination; and 63%, 95.6%, 72%, and 1.0%, respectively 24-months post-vaccination. Seropositivity was greater for Healive® than for H2 and Havrix® at 12 months (p-values a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine. PMID:27494260

  11. Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

    Science.gov (United States)

    Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

    2018-01-20

    The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

  12. Can a single dose of human papillomavirus (HPV) vaccine prevent cervical cancer? Early findings from an Indian study.

    Science.gov (United States)

    Sankaranarayanan, Rengaswamy; Joshi, Smita; Muwonge, Richard; Esmy, Pulikottil Okkuru; Basu, Partha; Prabhu, Priya; Bhatla, Neerja; Nene, Bhagwan M; Shaw, Janmesh; Poli, Usha Rani Reddy; Verma, Yogesh; Zomawia, Eric; Pimple, Sharmila; Tommasino, Massimo; Pawlita, Michael; Gheit, Tarik; Waterboer, Tim; Sehr, Peter; Pillai, Madhavan Radhakrishna

    2018-03-15

    Human papillomavirus (HPV) vaccination is a major strategy for preventing cervical and other ano-genital cancers. Worldwide HPV vaccination introduction and coverage will be facilitated if a single dose of vaccine is as effective as two or three doses or demonstrates significant protective effect compared to 'no vaccination'. In a multi-centre cluster randomized trial of two vs three doses of quadrivalent HPV vaccination (Gardasil™) in India, suspension of the vaccination due to events unrelated to the study led to per protocol and partial vaccination of unmarried 10-18 year old girls leading to four study groups, two by design and two by default. They were followed up for the primary outcomes of immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity for the vaccine-targeted HPV types and HPV infections. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one dose. One dose recipients demonstrated a robust and sustained immune response against HPV 16 and 18, albeit inferior to that of 3- or 2-doses and the antibody levels were stable over a 4 year period. The frequencies of cumulative incident and persistent HPV 16 and 18 infections up to 7 years of follow-up were similar and uniformly low in all the vaccinated study groups; the frequency of HPV 16 and 18 infections were significantly higher in unvaccinated age-matched control women than among vaccine recipients. The frequency of vaccine non-targeted HPV types was similar in the vaccinated groups but higher in the unvaccinated control women. Our results indicate that a single dose of quadrivalent HPV

  13. Comparison of 2 commercial single-dose Mycoplasma hyopneumoniae vaccines and porcine reproductive and respiratory syndrome virus (PRRSV) vaccines on pigs dually infected with M. hyopneumoniae and PRRSV.

    Science.gov (United States)

    Park, Changhoon; Kang, Ikjae; Seo, Hwi Won; Jeong, Jiwoon; Choi, Kyuhyung; Chae, Chanhee

    2016-04-01

    The objective of this study was to compare the efficacy of 2 different commercial Mycoplasma hyopneumoniae vaccines and porcine reproductive and respiratory syndrome virus (PRRSV) vaccines in regard to growth performance, microbiological and immunological analyses, and pathological observation from wean to finish (175 d of age). Pigs were administered M. hyopneumoniae and PRRSV vaccines at 7 and 21 d of age, respectively, or both at 21 d old and then challenged with both M. hyopneumoniae and PRRSV at 49 d old. Significant (P hyopneumoniae, M. hyopneumoniae-specific interferon-γ secreting cells, and macroscopic and microscopic lung lesions. Induction of interleukin-10 following PRRSV vaccination does not interfere with the immune responses induced by M. hyopneumoniae vaccine. The present study demonstrated that the single-dose vaccination regimen for M. hyopneumoniae and PRRSV vaccine is efficacious for controlling coinfection with M. hyopneumoniae and PRRSV based on clinical, microbiological, immunological, and pathological evaluation.

  14. Interaction between single-dose Mycoplasma hyopneumoniae and porcine reproductive and respiratory syndrome virus vaccines on dually infected pigs.

    Science.gov (United States)

    Park, Su-Jin; Seo, Hwi Won; Park, Changhoon; Chae, Chanhee

    2014-06-01

    The objective of this study was to determine the effects of Mycoplasma hyopneumoniae and/or porcine reproductive and respiratory syndrome virus (PRRSV) vaccination on dually infected pigs. In total, 72 pigs were randomly divided into nine groups (eight pigs per group), as follows: five vaccinated and challenged groups, three non-vaccinated and challenged groups, and a negative control group. Single-dose vaccination against M. hyopneumoniae alone decreased the levels of PRRSV viremia and PRRSV-induced pulmonary lesions, whereas single-dose vaccination against PRRSV alone did not decrease nasal shedding of M. hyopneumoniae and mycoplasma-induced pulmonary lesions in the dually infected pigs. The M. hyopneumoniae challenge impaired the protective cell-mediated immunity induced by the PRRSV vaccine, whereas the PRRSV challenge did not impair the protective cell-mediated immunity induced by the M. hyopneumoniae vaccine. The present study provides swine practitioners and producers with efficient vaccination regimes; vaccination against M. hyopneumoniae is the first step in protecting pigs against co-infection with M. hyopneumoniae and PRRSV. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage.

    Science.gov (United States)

    Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S

    2017-06-01

    In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

  16. Adapting to the global shortage of cholera vaccines: targeted single dose cholera vaccine in response to an outbreak in South Sudan.

    Science.gov (United States)

    Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Ciglenecki, Iza; Luquero, Francisco J; Azman, Andrew S; Cabrol, Jean-Clement

    2017-04-01

    Shortages of vaccines for epidemic diseases, such as cholera, meningitis, and yellow fever, have become common over the past decade, hampering efforts to control outbreaks through mass reactive vaccination campaigns. Additionally, various epidemiological, political, and logistical challenges, which are poorly documented in the literature, often lead to delays in reactive campaigns, ultimately reducing the effect of vaccination. In June 2015, a cholera outbreak occurred in Juba, South Sudan, and because of the global shortage of oral cholera vaccine, authorities were unable to secure sufficient doses to vaccinate the entire at-risk population-approximately 1 million people. In this Personal View, we document the first public health use of a reduced, single-dose regimen of oral cholera vaccine, and show the details of the decision-making process and timeline. We also make recommendations to help improve reactive vaccination campaigns against cholera, and discuss the importance of new and flexible context-specific dose regimens and vaccination strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Hepatitis A vaccine. A new convenient single-dose schedule with booster when long-term immunization is warranted

    DEFF Research Database (Denmark)

    Victor, J; Knudsen, J D; Nielsen, L P

    1994-01-01

    A total of 162 anti-HAV-negative healthy adults were immunized with a single high dose (1440 ELISA units = 1 ml) of inactivated hepatitis A vaccine and a booster was given at month 6. Antibodies were measured after modification of a commercial ELISA kit, enabling quantification of titres down to 6...

  18. A Randomised Trial Evaluating the Safety and Immunogenicity of the Novel Single Oral Dose Typhoid Vaccine M01ZH09 in Healthy Vietnamese Children

    NARCIS (Netherlands)

    Tran, T.H.; Nguyen, T.D.; Nguyen, T.T.; Ninh, T.T.V.; Tran, N.B.C.; Nguyen, V.M.H.; Tran, T.T.N.; Cao, T.T.; Pham, V.M.; Nguyen, T.C.B.; Tran, T.D.H.; Pham, V.T.; To, S.D.; Campbell, J.I.; Stockwell, E.; Schultsz, C.; Simmons, C.P.; Glover, C.; Lam, W.; Marques, F.; May, J.P.; Upton, A.; Budhram, R.; Dougan, G.; Farrar, J.; Nguyen, V.V.C.; Dolecek, C.

    2010-01-01

    Background: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)

  19. A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children

    NARCIS (Netherlands)

    Tran, Tinh Hien; Nguyen, Thi Dung; Nguyen, Thanh Truong; Ninh, Thi Thanh Van; Tran, Nguyen Bich Chau; Nguyen, Van Minh Hoang; Tran, Thi Thu Nga; Cao, Thu Thuy; Pham, Van Minh; Nguyen, Thi Cam Binh; Tran, Thi Diem Ha; Pham, Van Toi; To, Song Diep; Campbell, James I.; Stockwell, Elaine; Schultsz, Constance; Simmons, Cameron P.; Glover, Clare; Lam, Winnie; Marques, Filipe; May, James P.; Upton, Anthony; Budhram, Ronald; Dougan, Gordon; Farrar, Jeremy; Nguyen, Van Vinh Chau; Dolecek, Christiane

    2010-01-01

    The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)ssaV(-)) ZH9 with

  20. Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters

    Directory of Open Access Journals (Sweden)

    Joseph Prescott

    2014-01-01

    Full Text Available Andes virus (ANDV is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G. This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure, and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025, but animals were not significantly protected following 1 year of vaccination (p = 0.090. The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity.

  1. Design and statistical considerations for studies evaluating the efficacy of a single dose of the human papillomavirus (HPV) vaccine.

    Science.gov (United States)

    Sampson, Joshua N; Hildesheim, Allan; Herrero, Rolando; Gonzalez, Paula; Kreimer, Aimee R; Gail, Mitchell H

    2018-05-01

    Cervical cancer is a leading cause of cancer mortality in women worldwide. Human papillomavirus (HPV) types 16 and 18 cause about 70% of all cervical cancers. Clinical trials have demonstrated that three doses of either commercially available HPV vaccine, Cervarix ® or Gardasil ®, prevent most new HPV 16/18 infections and associated precancerous lesions. Based on evidence of immunological non-inferiority, 2-dose regimens have been licensed for adolescents in the United States, European Union, and elsewhere. However, if a single dose were effective, vaccine costs would be reduced substantially and the logistics of vaccination would be greatly simplified, enabling vaccination programs in developing countries. The National Cancer Institute (NCI) and the Agencia Costarricense de Investigaciones Biomédicas (ACIB) are conducting, with support from the Bill & Melinda Gates Foundation and the International Agency for Research on Cancer (IARC), a large 24,000 girl study to evaluate the efficacy of a 1-dose regimen. The first component of the study is a four-year non-inferiority trial comparing 1- to 2-dose regimens of the two licensed vaccines. The second component is an observational study that estimates the vaccine efficacy (VE) of each regimen by comparing the HPV infection rates in the trial arms to those in a contemporaneous survey group of unvaccinated girls. In this paper, we describe the design and statistical analysis for this study. We explain the advantage of defining non-inferiority on the absolute risk scale when the expected event rate is near 0 and, given this definition, suggest an approach to account for missing clinic visits. We then describe the problem of estimating VE in the absence of a randomized placebo arm and offer our solution. Copyright © 2018. Published by Elsevier Inc.

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

    Science.gov (United States)

    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

  3. Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study.

    Science.gov (United States)

    Huttner, Angela; Agnandji, Selidji Todagbe; Combescure, Christophe; Fernandes, José F; Bache, Emmanuel Bache; Kabwende, Lumeka; Ndungu, Francis Maina; Brosnahan, Jessica; Monath, Thomas P; Lemaître, Barbara; Grillet, Stéphane; Botto, Miriam; Engler, Olivier; Portmann, Jasmine; Siegrist, Denise; Bejon, Philip; Silvera, Peter; Kremsner, Peter; Siegrist, Claire-Anne

    2018-04-04

    The recombinant vesicular stomatitis virus (rVSV) vaccine expressing the Zaire Ebola virus (ZEBOV) glycoprotein is efficacious in the weeks following single-dose injection, but duration of immunity is unknown. We aimed to assess antibody persistence at 1 and 2 years in volunteers who received single-dose rVSV-ZEBOV in three previous trials. In this observational cohort study, we prospectively followed-up participants from the African and European phase 1 rVSV-ZEBOV trials, who were vaccinated once in 2014-15 with 300 000 (low dose) or 10-50 million (high dose) plaque-forming units (pfu) of rVSV-ZEBOV vaccine to assess ZEBOV glycoprotein (IgG) antibody persistence. The primary outcome was ZEBOV glycoprotein-specific IgG geometric mean concentrations (GMCs) measured yearly by ELISA compared with 1 month (ie, 28 days) after immunisation. We report GMCs up to 2 years (Geneva, Switzerland, including neutralising antibodies up to 6 months) and 1 year (Lambaréné, Gabon; Kilifi, Kenya) after vaccination and factors associated with higher antibody persistence beyond 6 months, according to multivariable analyses. Trials and the observational study were registered at ClinicalTrials.gov (Geneva: NCT02287480 and NCT02933931; Kilifi: NCT02296983) and the Pan-African Clinical Trials Registry (Lambaréné PACTR201411000919191). Of 217 vaccinees from the original studies (102 from the Geneva study, 75 from the Lambaréné study, and 40 from the Kilifi study), 197 returned and provided samples at 1 year (95 from the Geneva study, 63 from the Lambaréné, and 39 from the Kilifi study) and 90 at 2 years (all from the Geneva study). In the Geneva group, 44 (100%) of 44 participants who had been given a high dose (ie, 10-50 million pfu) of vaccine and who were seropositive at day 28 remained seropositive at 2 years, whereas 33 (89%) of 37 who had been given the low dose (ie, 300 000 pfu) remained seropositive for 2 years (p=0·042). In participants who had received a high dose

  4. Sustained Antibody Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent Human Papillomavirus (HPV) Vaccine in Adolescent Fijian Girls, and Subsequent Responses to a Single Dose of Bivalent HPV Vaccine: A Prospective Cohort Study.

    Science.gov (United States)

    Toh, Zheng Quan; Russell, Fiona M; Reyburn, Rita; Fong, James; Tuivaga, Evelyn; Ratu, Tupou; Nguyen, Cattram D; Devi, Rachel; Kama, Mike; Matanitobua, Silivia; Tabrizi, Sepehr N; Garland, Suzanne M; Sinha, Rohit; Frazer, Ian; Tikoduadua, Lisi; Kado, Joseph; Rafai, Eric; Mulholland, Edward K; Licciardi, Paul V

    2017-04-01

    The duration of antibody response following reduced human papillomavirus (HPV) vaccine doses has not been determined. We compared the antibody responses in girls previously vaccinated with zero, 1, 2, or 3 doses of quadrivalent HPV vaccine (4vHPV; Gardasil, Merck) 6 years previously. A prospective cohort study was undertaken in 200 Fijian girls 15-19 years of age. Approximately equal numbers of girls from 2 main ethnic groups (Fijians of Indian descent [FID] and Indigenous Fijians [iTaukei]) in Fiji were recruited for each dosage groups. Blood was drawn before and 28 days following a single dose of bivalent HPV vaccine (2vHPV; Cervarix, GlaxoSmithKline). We measured neutralizing antibodies (NAb) against HPV-6, -11, -16, and -18 using the pseudovirion-based neutralization assay. After 6 years (before a dose of 2vHPV was given), the geometric mean NAb titers for all 4 HPV types were not statistically different between 2-dose (2D) and 3-dose (3D) recipients: HPV-6 (3D: 2216 [95% confidence interval {CI},1695-2896]; 2D: 1476 [95% CI, 1019-2137]; P = .07), HPV-11 (3D: 4431 [95% CI, 3396-5783]; 2D: 2951 [95% CI, 1984-4390]; P = .09), HPV-16 (3D: 3373 [95% CI, 2511-4530]; 2D: 3275 [95% CI, 2452-4373]; P = .89); HPV-18 (3D: 628 [95% CI: 445-888]; 2D: 606 [95% CI, 462-862]; P = .89), and were higher in FID than iTaukei girls. Although 1-dose recipients had significantly lower NAb titers than 2-/3-dose recipients, their NAb titers were 5- to 30-fold higher than unvaccinated girls. Post-2vHPV NAb titers against HPV-16 and -18 were not statistically different between girls who received 1, 2, or 3 doses of 4vHPV previously. Two doses of 4vHPV provide similar NAb titers as 3 doses for 6 years, although the clinical significance is unknown. A single dose of 4vHPV elicits antibodies that persisted for at least 6 years, and induced immune memory, suggesting possible protection against HPV vaccine types after a single dose of 4vHPV. © The Author 2016. Published by Oxford University

  5. Single-dose vaccines save livestock and livelihoods in Sub-Saharan ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    South Africa's industry accounts for approximately 49% of agricultural gross domestic product, with an average annual turnover of US$13 billion. Vaccines for healthier livestock Vaccination is a critical tool to help reduce the number of livestock losses to viral infections. This project builds on the Canadian International Food ...

  6. Bluetongue Disabled Infectious Single Animal (DISA) vaccine: Studies on the optimal route and dose in sheep

    NARCIS (Netherlands)

    Rijn, van P.A.; Daus, F.J.; Maris-Veldhuis, M.A.; Feenstra, Femke; Gennip, van H.G.P.

    2016-01-01

    Bluetongue (BT) is a disease of ruminants caused by bluetongue virus (BTV) transmitted by biting midges of the Culicoides genus. Outbreaks have been controlled successfully by vaccination, however, currently available BT vaccines have several shortcomings. Recently, we have developed BT Disabled

  7. Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor.

    Science.gov (United States)

    Chen, Wilbur H; Cohen, Mitchell B; Kirkpatrick, Beth D; Brady, Rebecca C; Galloway, David; Gurwith, Marc; Hall, Robert H; Kessler, Robert A; Lock, Michael; Haney, Douglas; Lyon, Caroline E; Pasetti, Marcela F; Simon, Jakub K; Szabo, Flora; Tennant, Sharon; Levine, Myron M

    2016-06-01

    No licensed cholera vaccine is presently available in the United States. Cholera vaccines available in other countries require 2 spaced doses. A single-dose cholera vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2-dose immunization regimens impractical would be a major advance.PXVX0200, based on live attenuated Vibrio cholerae O1 classical Inaba vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this vaccine in a human cholera challenge model. Consenting healthy adult volunteers, 18-45 years old, were randomly allocated 1:1 to receive 1 oral dose of vaccine (approximately 5 × 10(8) colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 × 10(5) CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration. The vaccine was well tolerated, with no difference in adverse event frequency among 95 vaccinees vs 102 placebo recipients. The primary endpoint, moderate (≥3.0 L) to severe (≥5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) vaccinees at 10 days (vaccine efficacy, 90.3%; P < .0001) and 4 of 33 (12.1%) vaccinees at 3 months (vaccine efficacy, 79.5%; P < .0001). The significant vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose cholera vaccine. NCT01895855. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  8. Seroprevalence of influenza A H1N1 and seroconversion of mothers and infants induced by a single dose of monovalent vaccine.

    Science.gov (United States)

    Chao, Anne; Huang, Yhu-Chering; Chang, Yao-Lung; Wang, Tzu-Hao; Chang, Shuenn-Dyh; Wu, Ting-Shu; Wu, Tsu-Lan; Chao, An-Shine

    2013-09-01

    To determine the prevalence of preexisting antibodies against the pandemic 2009 Influenza A (H1N1) virus in pregnant women and to evaluate the seroprotection of the mothers and infants by a single injection of monovalent vaccine during the pandemic. Seropositivity rate of H1N1 among the nonvaccinated were compared with the vaccinated women. A single dose of vaccine, either nonadjuvanted AdimFlu-S or MF59-adjuvanted vaccine, was injected to the voluntarily vaccinated group. Maternal and cord blood sera were collected to evaluate the antibody response of the H1N1 virus. Seropositivity was defined as a hemagglutination inhibition titer to H1N1 (A/Taiwan/126/09) ≥ 1:40. A total of 210 healthy, singleton, pregnant women were enrolled between January 2010 and May 2010. Seropositivity (≥ 1:40) of maternal hemagglutination inhibition was significantly higher in the vaccinated group (78%) than the nonvaccinated group (9.5%); 41.6% (20/48) of seropositive titers were >1:80. In nine vaccinated cases resulting in negative serum titers (75% could be achieved in the paired maternal and cord serum samples by a single injection of monovalent H1N1 vaccine. Copyright © 2013. Published by Elsevier B.V.

  9. Single Dose of Consensus Hemagglutinin-Based Virus-Like Particles Vaccine Protects Chickens against Divergent H5 Subtype Influenza Viruses

    Directory of Open Access Journals (Sweden)

    Peipei Wu

    2017-11-01

    Full Text Available The H5 subtype highly pathogenic avian influenza (HPAI virus is one of the greatest threats to global poultry industry. To develop broadly protective H5 subunit vaccine, a recombinant consensus HA sequence (rHA was constructed and expressed in virus-like particles (rHA VLPs in the baculovirus-insect cell system. The efficacy of the rHA VLPs vaccine with or without immunopotentiator (CVCVA5 was assessed in chickens. Compared to the commercial Re6 or Re6-CVCVA5 vaccines, single dose immunization of chickens with rHA VLPs or rHA-CVCVA5 vaccines induced higher levels of serum hemagglutinin inhibition titers and neutralization titers, mucosal antibodies, IFN-γ and IL-4 cytokines in sera, and cytotoxic T lymphocyte responses. The rHA VLPs vaccine was superior to the commercial Re6 vaccine in conferring cross-protection against different clades of H5 subtype viruses. This study reports that H5 subtype consensus HA VLP single dose vaccination provides broad protection against HPAI virus in chickens.

  10. Development of a single-dose recombinant CAMP factor entrapping poly(lactide-co-glycolide) microspheres-based vaccine against Streptococcus agalactiae.

    Science.gov (United States)

    Liu, Gang; Yin, Jinhua; Barkema, Herman W; Chen, Liben; Shahid, Muhammad; Szenci, Otto; De Buck, Jeroen; Kastelic, John P; Han, Bo

    2017-03-01

    Streptococcus agalactiae is an important contagious bovine mastitis pathogen. Although it is well controlled and even eradicated in most Northern European and North American dairy herds, the prevalence of this pathogen remains very high in China. However, research on development of a vaccine against S. agalactiae mastitis is scarce. The aims of the present study were to: (1) develop a single-dose vaccine against S. agalactiae based on poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) encapsulated CAMP factor, a conserved virulent protein encoded by S. agalactiae's cfb gene; and (2) evaluate its immunogenicity and protective efficacy in a mouse model. The cfb gene was cloned and expressed in a recombinant Escherichia coli strain Trans1-T1. The CAMP factor was tested to determine a safe dose range and then encapsulated in MS of PLGA (50:50) to assess its release pattern in vitro and immune reaction in vivo. Furthermore, a mouse model and a histopathological assay were developed to evaluate bacterial burden and vaccine efficacy. In the low dosage range (S. agalactiae challenge. Additionally, no pathological lesions were detected in the vaccinated group. Therefore, PLGA-CAMP conferred protective efficacy against S. agalactiae in our mouse model, indicating its potential as a vaccine against S. agalactiae mastitis. Furthermore, the slow-release kinetics of PLGA MS warranted optimism for development of a single-dose vaccine. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  11. A new single-dose bivalent vaccine of porcine circovirus type 2 and Mycoplasma hyopneumoniae elicits protective immunity and improves growth performance under field conditions.

    Science.gov (United States)

    Jeong, Jiwoon; Park, Changhoon; Choi, Kyuhyung; Chae, Chanhee

    2016-01-15

    The efficacy of the new single-dose bivalent vaccine of porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae was evaluated under field conditions for registration as recommended by the Republic of Korea's Animal, Plant & Fisheries Quarantine & Inspection Agency. Three farms were selected based on their history of co-infection with PCV2 and M. hyopneumoniae. On each farm, a total of 80 3-week-old pigs were randomly allocated to one of two treatment groups: (i) vaccinated (n=40) and (ii) unvaccinated (n=40) animals at 3 weeks of age. Protection by the bivalent vaccine helped increase the market weight by 6.2 kg/pig (106.2 kg in vaccinated group vs. 100 kg in unvaccinated group; Phyopneumoniae-specific IFN-γ-SC. Vaccinated animals displayed a reduced PCV2 load in the blood and M. hyopneumoniae load in nasal swabs compared to unvaccinated animals. Vaccination of pigs against PCV2 and M. hyopneumoniae effectively reduced the lung and lymphoid lesion scores compared to unvaccinated animals in all 3 farms. The new bivalent vaccine is very efficacious in controlling PCV2 and M. hyopneumoniae infection based on clinical, immunological, virological, and pathological evaluations under field conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Single visit rabies pre-exposure priming induces a robust anamnestic antibody response after simulated post-exposure vaccination: results of a dose-finding study.

    Science.gov (United States)

    Jonker, Emile F F; Visser, Leonardus G

    2017-09-01

    The current standard 3-dose intramuscular rabies PrEP schedule suffers from a number of disadvantages that severely limit accessibility and availability. The cost of is often prohibitive, it requires 3 visits to the clinic, and there are regular vaccine shortages. Volunteers ( N  = 30) were randomly assigned to 4 study arms: 1 standard dose intramuscular (IM) dose of PVRV (purified Vero cell rabies vaccine, Verorab), and 1/5th, 2/5th or 3/5th- fractional intradermal (ID) dose of PVRV in a single visit. All subjects received a simulated rabies post-exposure prophylaxis (D0, D3) 1 year later. Rabies virus neutralizing antibodies (RVNA) were determined by virus neutralization microtest (FAVN) on D0, D7, D28, Y1 and Y1 + D7. 28 out of 30 subjects (93%) seroconverted 1 month after primary vaccination; 1 subject in the 1-dose IM arm and 1 in the 1/5th-fractional dose ID arm did not. After 1 year, 22 out of 30 subjects (73%) no longer had RVNA above 0.5 IU/ml, with no discernible difference between study groups. After 1 year, all 30 subjects mounted a booster response within 7 days after simulated PEP, with the highest titers found in the single dose IM group ( P  rabies vaccine was sufficient to induce an adequate anamnestic antibody response to rabies PEP in all subjects 1 year later, even in those in whom the RVNA threshold of 0.5 IU/ml was not reached after priming. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  13. Comparative Assessment of a Single Dose and a 2-dose Vaccination Series of a Quadrivalent Meningococcal CRM-conjugate Vaccine (MenACWY-CRM) in Children 2-10 Years of Age.

    Science.gov (United States)

    Johnston, William; Essink, Brandon; Kirstein, Judith; Forleo-Neto, Eduardo; Percell, Sandra; Han, Linda; Keshavan, Pavitra; Smolenov, Igor

    2016-01-01

    We compared the immunogenicity, safety and 1-year antibody persistence of a single-dose and a 2-dose series of a licensed meningococcal ACWY-CRM conjugate vaccine (MenACWY-CRM) in 2- to 10-year-old children. In this phase III, multicenter, observer-blind study, children aged 2-5 years (n = 359) and 6-10 years (n = 356) were randomized 1:1 to receive 2 doses of MenACWY-CRM (ACWY2) or 1 dose of placebo followed by 1 dose of MenACWY-CRM (ACWY1), 2 months apart. Immunogenicity was measured using serum bactericidal activity with human complement (hSBA). Primary outcomes were to assess the immunologic noninferiority and superiority of ACWY2 versus ACWY1. One-month after the second dose, the hSBA seroresponse in ACWY2 was noninferior to ACWY1 for all 4 serogroups, in both age cohorts, and was superior for serogroups C and Y in the 2- to 5-year-old age cohort and for serogroup Y in the 6- to 10-year-old age cohort. Overall, 90%-99% of subjects in ACWY2 and 65%-96% in ACWY1 had hSBA titers ≥ 8; geometric mean titers were 1.8- to 6.4-fold higher in ACWY2 than ACWY1 across serogroups. At 1 year postvaccination, geometric mean titers declined, and the differences between ACWY2 and ACWY1 remained significant for serogroups A and C in the 2- to 5-year-old age cohort and for serogroups C and Y in the 6- to 10-year-old age cohort. The safety profile of MenACWY-CRM was similar in both groups. The single dose and 2-dose MenACWY-CRM series were immunogenic and well tolerated. Although antibody responses were greater after 2 doses, especially in the 2- to 5-year-old age cohort, this difference was less pronounced at 1 year postvaccination.

  14. Reduced lung lesions in pigs challenged 25 weeks after the administration of a single dose of Mycoplasma hyopneumoniae vaccine at approximately 1 week of age.

    Science.gov (United States)

    Reynolds, S C; St Aubin, L B; Sabbadini, L G; Kula, J; Vogelaar, J; Runnels, P; Peters, A R

    2009-09-01

    Two independent studies assessed the duration of immunity of an inactivated adjuvanted Mycoplasma hyopneumoniae vaccine against mycoplasmal pneumonia in seronegative (study A, n=52) and seropositive (study B, n=52) pigs. The pigs were allocated randomly to treatment and were then injected with a single dose of either the vaccine or a placebo at approximately 1 week of age. Twenty-five weeks after treatment administration, the pigs were challenged with a virulent strain (LI 36, Strain 232) of M. hyopneumoniae and the extent of lung lesions consistent with mycoplasmal pneumonia was assessed 4 weeks later. In study A, the geometric mean lung lesion score (expressed as least squares mean percentages of lung lesions) was significantly (P=0.0001) lower in vaccinated (0.3%, n=20) than in control pigs (5.9%, n=24) seronegative to M. hyopneumoniae at enrolment; similarly, in study B, the extent of lung lesions was significantly reduced (P=0.0385) in seropositive vaccinated pigs (2.0%, n=22) compared to controls (4.5%, n=26). At the end of the investigation period, 4 weeks after challenge, mean antibody sample-to-positive (S/P) ratios were significantly higher both in seronegative (P=0.0012) and seropositive (P=0.0001) vaccinated pigs (mean values=0.77 and 0.81, respectively) than in controls (mean values=0.51 and 0.38, respectively).

  15. Immunogenicity and protective efficacy of a single-dose live non-pathogenic Escherichia coli oral vaccine against F4-positive enterotoxigenic Escherichia coli challenge in pigs.

    Science.gov (United States)

    Fairbrother, John Morris; Nadeau, Éric; Bélanger, Louise; Tremblay, Cindy-Love; Tremblay, Danielle; Brunelle, Mélanie; Wolf, Regina; Hellmann, Klaus; Hidalgo, Álvaro

    2017-01-05

    Enterotoxigenic Escherichia coli strains expressing F4 (K88) fimbriae (F4-ETEC) are one of the most important causes of post-weaning diarrhea (PWD) in pigs. F4, a major antigen, plays an important role in the early steps of the infection. Herein, the efficacy of a live oral vaccine consisting of a non-pathogenic E. coli strain expressing F4 for protection of pigs against PWD was evaluated. Three blinded, placebo-controlled, block design, parallel-group confirmatory experiments were conducted, using an F4-ETEC PWD challenge model, each with a different vaccination-challenge interval (3, 7, and 21days). The pigs were vaccinated via the drinking water with a single dose of the Coliprotec® F4 vaccine one day post-weaning. Efficacy was assessed by evaluating diarrhea, clinical observations, intestinal fluid accumulation, weight gain, intestinal colonization and fecal shedding of F4-ETEC. The immune response was evaluated by measuring serum and intestinal F4-specific antibodies. The administration of the vaccine resulted in a significant reduction of the incidence of moderate to severe diarrhea, ileal colonization by F4-ETEC, and fecal shedding of F4-ETEC after the heterologous challenge at 7 and 21days post-vaccination. The 7-day onset of protection was associated with an increase of serum anti-F4 IgM whereas the 21-day duration of protection was associated with an increase of both serum anti-F4 IgM and IgA. Significant correlations between levels of serum and intestinal secretory anti-F4 antibodies were detected. Maternally derived F4-specific serum antibodies did not interfere with the vaccine efficacy. The evaluation of protection following a challenge three days after vaccination showed a reduction of the severity and the duration of diarrhea and of fecal shedding of F4-ETEC. The 7-day onset and the 21-day duration of protection induced by Coliprotec® F4 vaccine administered once in drinking water to pigs of at least 18days of age were confirmed by protection

  16. Novel Insect-Specific Eilat Virus-Based Chimeric Vaccine Candidates Provide Durable, Mono- and Multivalent, Single-Dose Protection against Lethal Alphavirus Challenge.

    Science.gov (United States)

    Erasmus, Jesse H; Seymour, Robert L; Kaelber, Jason T; Kim, Dal Y; Leal, Grace; Sherman, Michael B; Frolov, Ilya; Chiu, Wah; Weaver, Scott C; Nasar, Farooq

    2018-02-15

    Most alphaviruses are mosquito borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. Recently, a host-restricted, mosquito-borne alphavirus, Eilat virus (EILV), was described with an inability to infect vertebrate cells based on defective attachment and/or entry, as well as a lack of genomic RNA replication. We investigated the utilization of EILV recombinant technology as a vaccine platform against eastern (EEEV) and Venezuelan equine encephalitis viruses (VEEV), two important pathogens of humans and domesticated animals. EILV chimeras containing structural proteins of EEEV or VEEV were engineered and successfully rescued in Aedes albopictus cells. Cryo-electron microscopy reconstructions at 8 and 11 Å of EILV/VEEV and EILV/EEEV, respectively, showed virion and glycoprotein spike structures similar to those of VEEV-TC83 and other alphaviruses. The chimeras were unable to replicate in vertebrate cell lines or in brains of newborn mice when injected intracranially. Histopathologic examinations of the brain tissues showed no evidence of pathological lesions and were indistinguishable from those of mock-infected animals. A single-dose immunization of either monovalent or multivalent EILV chimera(s) generated neutralizing antibody responses and protected animals against lethal challenge 70 days later. Lastly, a single dose of monovalent EILV chimeras generated protective responses as early as day 1 postvaccination and partial or complete protection by day 6. These data demonstrate the safety, immunogenicity, and efficacy of novel insect-specific EILV-based chimeras as potential EEEV and VEEV vaccines. IMPORTANCE Mostly in the last decade, insect-specific viruses have been discovered in several arbovirus families. However, most of these viruses are not well studied and largely have been ignored. We explored the use of the mosquito-specific alphavirus EILV as an alphavirus vaccine

  17. MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization.

    Directory of Open Access Journals (Sweden)

    Joost H C M Kreijtz

    Full Text Available Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amount of vaccine preparations that can be produced is limited. Furthermore, protective immunity is induced ideally after a single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccine were assessed in mice. To this end, mice were vaccinated once or twice with descending doses of a recombinant MVA expressing the HA gene of influenza virus A/Vietnam/1194/04. The protective efficacy was determined after challenge infection with the homologous clade 1 virus and a heterologous virus derived from clade 2.1, A/Indonesia/5/05 by assessing weight loss, virus replication and histopathological changes. It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate.

  18. Single-dose mucosal immunization with a candidate universal influenza vaccine provides rapid protection from virulent H5N1, H3N2 and H1N1 viruses.

    Directory of Open Access Journals (Sweden)

    Graeme E Price

    2010-10-01

    Full Text Available The sudden emergence of novel influenza viruses is a global public health concern. Conventional influenza vaccines targeting the highly variable surface glycoproteins hemagglutinin and neuraminidase must antigenically match the emerging strain to be effective. In contrast, "universal" vaccines targeting conserved viral components could be used regardless of viral strain or subtype. Previous approaches to universal vaccination have required protracted multi-dose immunizations. Here we evaluate a single dose universal vaccine strategy using recombinant adenoviruses (rAd expressing the conserved influenza virus antigens matrix 2 and nucleoprotein.In BALB/c mice, administration of rAd via the intranasal route was superior to intramuscular immunization for induction of mucosal responses and for protection against highly virulent H1N1, H3N2, or H5N1 influenza virus challenge. Mucosally vaccinated mice not only survived, but had little morbidity and reduced lung virus titers. Protection was observed as early as 2 weeks post-immunization, and lasted at least 10 months, as did antibodies and lung T cells with activated phenotypes. Virus-specific IgA correlated with but was not essential for protection, as demonstrated in studies with IgA-deficient animals.Mucosal administration of NP and M2-expressing rAd vectors provided rapid and lasting protection from influenza viruses in a subtype-independent manner. Such vaccines could be used in the interval between emergence of a new virus strain and availability of strain-matched vaccines against it. This strikingly effective single-dose vaccination thus represents a candidate off-the-shelf vaccine for emergency use during an influenza pandemic.

  19. A single dose of live-attenuated 638 Vibrio cholerae oral vaccine is safe and immunogenic in adult volunteers in Mozambique

    Directory of Open Access Journals (Sweden)

    Hilda María García

    2011-12-01

    Full Text Available A placebo-controlled randomized, double-blind, clinical trial was carried out to assess the safety, reactogenicity, and immunogenicity of the lyophilized vaccine candidate against cholera derived from the live attenuated 638 Vibrio cholerae O1 El Tor Ogawa strain. One hundred and twenty presumably healthy female and male adult volunteers aged between 18 and 50 years were included. They were from Maputo, Mozambique a cholera endemic area, where, in addition, human immunodeficiency virus (HIV seroprevalence is from 20 to 30%. A dose of 2 x 10 9 colony forming units (CFU was given to 80 subjects and other 40 received only vaccine lyoprotectors as a placebo control. Out-patient follow-up of adverse events was carried out during the following 30 days after vaccination. The immune response was evaluated by the estimation of seroconversion rate and the geometric mean titer (GMT of vibriocidal antibodies in the sera from volunteers that was collected previously, and at days 14 and 21 after immunization. No serious adverse events were reported. The adverse events found in the vaccine group were similar to those of the placebo groups. They were independent from the detection of antibodies against HIV-1, HIV-2, hepatitis (H A; HC and hepatitis B surface antigen. The presence of helminthes did not modify the incidence of adverse events. The 638 vaccine strain was isolated in 37 (46.25% vaccinated volunteer's feces. The peak of the GMT of vibriocidal antibodies in the vaccine group was 9056 versus 39 in the placebo group at 14 days with a total seroconversion of 97.4% at 21 days. The 638 vaccine candidate is safe and immunogenic in a cholera endemic region.

  20. Efficacy of single dose of a bivalent vaccine containing inactivated Newcastle disease virus and reassortant highly pathogenic avian influenza H5N1 virus against lethal HPAI and NDV infection in chickens.

    Directory of Open Access Journals (Sweden)

    Dong-Hun Lee

    Full Text Available Highly pathogenic avian influenza (HPAI and Newcastle disease (ND are 2 devastating diseases of poultry, which cause great economic losses to the poultry industry. In the present study, we developed a bivalent vaccine containing antigens of inactivated ND and reassortant HPAI H5N1 viruses as a candidate poultry vaccine, and we evaluated its immunogenicity and protective efficacy in specific pathogen-free chickens. The 6:2 reassortant H5N1 vaccine strain containing the surface genes of the A/Chicken/Korea/ES/2003(H5N1 virus was successfully generated by reverse genetics. A polybasic cleavage site of the hemagglutinin segment was replaced by a monobasic cleavage site. We characterized the reverse genetics-derived reassortant HPAI H5N1 clade 2.5 vaccine strain by evaluating its growth kinetics in eggs, minimum effective dose in chickens, and cross-clade immunogenicity against HPAI clade 1 and 2. The bivalent vaccine was prepared by emulsifying inactivated ND (La Sota strain and reassortant HPAI viruses with Montanide ISA 70 adjuvant. A single immunization with this vaccine induced high levels of hemagglutination-inhibiting antibody titers and protected chickens against a lethal challenge with the wild-type HPAI and ND viruses. Our results demonstrate that the bivalent, inactivated vaccine developed in this study is a promising approach for the control of both HPAI H5N1 and ND viral infections.

  1. Vaccine vial stopper performance for fractional dose delivery of vaccines.

    Science.gov (United States)

    Jarrahian, Courtney; Myers, Daniel; Creelman, Ben; Saxon, Eugene; Zehrung, Darin

    2017-07-03

    Shortages of vaccines such as inactivated poliovirus and yellow fever vaccines have been addressed by administering reduced-or fractional-doses, as recommended by the World Health Organization Strategic Advisory Group of Experts on Immunization, to expand population coverage in countries at risk. We evaluated 3 kinds of vaccine vial stoppers to assess their performance after increased piercing from repeated withdrawal of doses needed when using fractional doses (0.1 mL) from presentations intended for full-dose (0.5 mL) delivery. Self-sealing capacity and fragmentation of the stopper were assessed via modified versions of international standard protocols. All stoppers maintained self-sealing capacity after 100 punctures. The damage to stoppers measured as the fragmentation rate was within the target of ≤ 10% of punctures resulting in a fragment after as many as 50 punctures. We concluded that stopper failure is not likely to be a concern if existing vaccine vials containing up to 10 regular doses are used up to 50 times for fractional dose delivery.

  2. Nasopharyngeal Pneumococcal Colonization and Impact of a Single Dose of 13-Valent Pneumococcal Conjugate Vaccine in Indian Children With HIV and Their Unvaccinated Parents.

    Science.gov (United States)

    Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Ganaie, Feroze; Bhaskar, Arun; Bhattacharyya, Subhasish; Niyogi, Swapan Kumar; Moss, William J; Panda, Samiran; Ravikumar, Kadahalli Lingegowda; Das, Ranjan Saurav; Mandal, Sutapa

    2018-05-01

    Human immunodeficiency virus (HIV) infection increases risk of invasive disease from Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV) prevent invasive disease and acquisition of vaccine type (VT) pneumococcus in the nasopharynx. To look at the safety and impact of one dose of PCV13 on acquisition of VT pneumococcal carriage in Indian children with HIV. We conducted a cohort study in families of HIV-infected children (CLH) and families of HIV-uninfected children (HUC) in West Bengal. All children received one dose of PCV13. Nasopharyngeal swabs were collected from children and parents at baseline and 2 months after vaccination. One hundred and fifteen CLH and 47 HUC received one dose of PCV13. Fifty-eight percent of CLH were on antiretroviral therapy (ART), and the median nadir CD4 count was 287. There were no significant adverse events in either group. HUC had more VT colonization than CLH-55% versus 23% of all pneumococcal isolates. HIV infection doubled the risk of nonvaccine serotype colonization (P = 0.03). There was no difference in acquisition of VT isolates in CLH (4.4%) and HUC (4.5%) post-PCV13; however, older CLH (>5 years) had decreased clearance of VT strains. ART made no difference in pneumococcal colonization at baseline or after PCV13; however, CLH with higher nadir CD4 counts before starting ART were less likely to have VT colonization post-PCV13 (prevalence ratio, 0.2; 95% confidence interval: 0.1-0.5). While there was no difference in acquisition of VT nasopharyngeal carriage of pneumococcus in CLH and HUC after one dose of PCV13, earlier access to ART may impact response to PCV13 in CLH.

  3. Immunogenicity and safety of a single dose of a CRM-conjugated meningococcal ACWY vaccine in children and adolescents aged 2-18 years in Taiwan: results of an open label study.

    Science.gov (United States)

    Huang, Li-Min; Chiu, Nan-Chang; Yeh, Shu-Jen; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

    2014-09-08

    MenACWY-CRM (Menveo®, Novartis Vaccines, Siena, Italy) is a quadrivalent meningococcal conjugate vaccine developed to help prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W, and Y. It is approved within the European Union in persons >2 years of age and in persons from 2 months to 55 years of age in the United States, among other countries. Little is known about the immunogenicity and safety of this vaccine in Taiwanese children >2 years and adolescents. This study assessed the immunogenicity and safety of a single injection of MenACWY-CRM vaccine in Taiwanese subjects aged 2-18 years old. In this phase III, multicentre, open-label study 341 subjects received one dose of MenACWY-CRM. Immunogenicity measures were rates of seroresponse (defined as the proportion of subjects with a postvaccination hSBA ≥1:8 if the prevaccination (baseline) titre was CRM vaccination at Day 29 for the serogroups A, C, W, and Y were 83%, 93%, 50%, and 65%, respectively. At Day 29 the percentages of subjects with hSBA ≥1:8 against all four serogroups A, C, W and Y were: 83%, 96%, 96% and 82%, respectively. GMTs against all serogroups rose by ≥7-fold from baseline to Day 29. The vaccine was well tolerated. A single dose of MenACWY-CRM demonstrated a robust immune response, and an acceptable safety profile in Taiwanese children and adolescents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Pharmacokinetic comparison of acetaminophen elixir versus suppositories in vaccinated infants (aged 3 to 36 months): a single-dose, open-label, randomized, parallel-group design.

    Science.gov (United States)

    Walson, Philip D; Halvorsen, Mark; Edge, James; Casavant, Marcel J; Kelley, Michael T

    2013-02-01

    Because of practical problems and ethical concerns, few studies of the pharmacokinetics (PK) of acetaminophen (ACET) in infants have been published. The goal of this study was to compare the PK of an ACET rectal suppository with a commercially available ACET elixir to complete a regulatory obligation to market the suppository. This study was not submitted previously because of numerous obstacles related to both the investigators and the commercial entities associated with the tested product. Thirty infants (age 3-36 months) prescribed ACET for either fever, pain, or postimmunization prophylaxis of fever and discomfort were randomized to receive a single 10- to 15-mg/kg ACET dose either as the rectal suppository or oral elixir. Blood was collected at selected times for up to 8 hours after administration. ACET concentrations were measured by using a validated HPLC method, and PK behavior and bioavailability were compared for the 2 preparations. All 30 infants enrolled were prescribed ACET for postimmunization prophylaxis. PK samples were available in 27 of the 30 enrolled infants. Subject enrollment (completed in January 1995) was rapid (8.3 months) and drawn entirely from a vaccinated infant clinic population. There were no statistically significant differences between the subjects (elixir, n = 12; suppository, n = 15) in either mean (SD) age (10.0 [6.3] vs 12.4 [8.1] months), weight (8.6 [2.3] vs 9.4 [2.4] kg), sex (7 of 12 males vs 7 of 15 males), or racial distribution (5 white, 5 black, and 2 biracial vs 4 white and 11 black) between the 2 dosing groups (oral vs rectal, respectively). The oral and rectal preparations produced similar, rapid peak concentrations (T(max), 1.16 vs 1.17 hours; P = 0.98) and elimination t(½) (1.84 vs 2.10 hours; P = 0.14), respectively. No statistically significant differences were found between either C(max) (7.65 vs 5.68 μg/mL) or total drug exposure (AUC(0-∞), 23.36 vs 20.45 μg-h/mL) for the oral versus rectal preparations

  5. The administration of a single dose of a multivalent (DHPPiL4R) vaccine prevents clinical signs and mortality following virulent challenge with canine distemper virus, canine adenovirus or canine parvovirus

    OpenAIRE

    Stephen Wilson; Joanna Illambas; Elisabeth Siedek; Anne Thomas; Vickie King; Catrina Stirling; Edita Plevová; Jeremy Salt; Gordon Sture

    2014-01-01

    Four challenge studies following vaccination of dogs with a multivalent vaccine containing canine parvovirus (CPV-2b), adenovirus (CAV-1/-2) and distemper (CDV) are described. Six week old puppies received a single vaccination while non-vaccinated control dogs received water. In each respective trial, groups of dogs were challenged 21 days after vaccination with heterologous viral isolates. Clinical observations, rectal temperature measurements, and blood and swab samples for analysis were co...

  6. Can a Compact Pre-Filled Auto-Disable Injection System (cPAD) Save Costs for DTP-HepB-Hib Vaccine as Compared with Single-Dose (SDV) and Multi-Dose Vials (MDV)? Evidence from Cambodia, Ghana, and Peru.

    Science.gov (United States)

    Nogier, Cyril; Hanlon, Patrick; Wiedenmayer, Karin; Maire, Nicolas

    2015-03-01

    A compact pre-filled auto-disable injection (cPAD) presentation is being developed for the fully liquid pentavalent DTP-HepB-Hib vaccine. A cost analysis (CA) to compare this presentation with the presently used single-dose vial (SDV) and multi-dose vial (MDV) was conducted in Cambodia, Ghana, and Peru. The CA included the development of an excel-based costing model and considered the costs of vaccine, safe injection equipment, procurement, storage, transport and distribution, vaccine administration by health staff, medical waste management, start-up activities, as well as coverage, birth cohort, vaccine, and safe injection equipment wastage rates. The outcome was the change in cost per pentavalent fully immunized child (PFIC) for a switch to cPAD. Field visits to health facilities, and interviews with key informants from immunization services and regulatory authorities, were conducted to collect data and to test the costing model in country context. Cost data were also obtained from manufacturers, published price lists, and author estimates. A sensitivity analysis (SA) was conducted to explore possible variations in values of data collected. Based on vaccine price trends estimated for 2016, cPAD is less costly in Ghana [incremental cost per PFIC: $US-0.59 (-6.46 %)] than the current presentation (ten-dose MDV) and in Peru (SDV): $US-0.89 (-7.14 %). In Cambodia, cPAD is more costly than SDV: $US+0.33 (+3.90 %). The most significant cost item per PFIC is the vaccine (reflecting wastage rates) in all presentations. The dominance of the vaccine price per dose and, to a lesser extent, the wastage rates in the incremental cost per PFIC show potential to simplify future analyses. Other relevant considerations at country level for a change of presentation include the potential for improved safety with cPAD, planned introduction of other vaccines, environmental and safety issues, and financial sustainability.

  7. A single dose of a DNA vaccine encoding apa coencapsulated with 6,6'-trehalose dimycolate in microspheres confers long-term protection against tuberculosis in Mycobacterium bovis BCG-primed mice.

    Science.gov (United States)

    Carlétti, Dyego; Morais da Fonseca, Denise; Gembre, Ana Flávia; Masson, Ana Paula; Weijenborg Campos, Lívia; Leite, Luciana C C; Rodrigues Pires, Andréa; Lannes-Vieira, Joseli; Lopes Silva, Célio; Bonato, Vânia Luiza Deperon; Horn, Cynthia

    2013-08-01

    Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.

  8. Yellow Fever Vaccine Booster Doses: Recommendations of the Advisory Committee on Immunization Practices, 2015.

    Science.gov (United States)

    Staples, J Erin; Bocchini, Joseph A; Rubin, Lorry; Fischer, Marc

    2015-06-19

    On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) voted that a single primary dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers. ACIP also approved recommendations for at-risk laboratory personnel and certain travelers to receive additional doses of yellow fever vaccine (Box). The ACIP Japanese Encephalitis and Yellow Fever Vaccines Workgroup evaluated published and unpublished data on yellow fever vaccine immunogenicity and safety. The evidence for benefits and risks associated with yellow fever vaccine booster doses was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This report summarizes the evidence considered by ACIP and provides the updated recommendations for yellow fever vaccine booster doses.

  9. Sero-Surveillance to assess immunity to rubella and assessment of immunogenicity and safety of a single dose of rubella vaccine in school girls

    Directory of Open Access Journals (Sweden)

    Sharma Hitt

    2010-01-01

    Full Text Available Background: Rubella vaccination is not yet included in National Immunization Schedule in India. Serosurvey is frequently used to assess epidemiologic pattern of Rubella in a community. Serosurveys in different parts of India have found that 6-47% of women are susceptible for Rubella infection. The present serosurveillance was conducted in Jammu, India, in two public schools. Objective: To determine serological status of Rubella antibodies of school girls and assessment of immunogenicity and reactogenicity of Rubella immunization in seronegative girls. Materials and Methods: The current study was conducted to determine Rubella serostatus in peripubertal schoolgirls aged 11-18 years and also to assess immunogenicity and safety of Rubella vaccine (R-Vac of Serum Institute of India Ltd., Pune, in seronegative girls. For screening, pre-vaccination serum Rubella IgG antibodies were determined and to assess immunogenicity of the vaccine, post-vaccination IgG antibodies were compared with pre-vaccination levels. Safety assessment was done for a period of 8 weeks, post-vaccination. Results: A total of 90 (32.7% seronegative girls were vaccinated. All girls (100% became seropositive, post-vaccination. Clinically relevant and statistically significant increase in anti-Rubella IgG titres was observed. The adverse events were mild and self-limiting. Conclusions: R-Vac vaccine used in the study demonstrated an excellent safety and immunogenicity profile.

  10. Randomized Trial of 2 Versus 1 Dose of Measles Vaccine

    DEFF Research Database (Denmark)

    Brønd, Marie; Martins, Cesario L; Byberg, Stine

    2018-01-01

    Background: Two doses of measles vaccine (MV) might reduce the nonmeasles mortality rate more than 1 dose of MV does. The effect of 2 versus 1 dose on morbidity has not been examined. Within a randomized trial of the effect of 2 doses versus 1 dose of MV on mortality in Guinea-Bissau, we investig...

  11. Intradermal inactivated poliovirus vaccine: a preclinical dose-finding study.

    Science.gov (United States)

    Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

    2015-05-01

    Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. Intradermal Inactivated Poliovirus Vaccine: A Preclinical Dose-Finding Study

    OpenAIRE

    Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

    2014-01-01

    Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial...

  13. Response of booster dose of cuban recombinant hepatitis-B vaccine in nonresponder and hyporesponder children

    International Nuclear Information System (INIS)

    Dahifar, H.; Mousavi, F.; Ghorbani, A.

    2007-01-01

    Acute hepatitis B infection can debilitate a patient for weeks and occasionally has a fatal outcome, while chronic infection is a major threat to the individual. To assess response of nonresponder and hyporesponder children to booster dose of Cuban recombinant hepatitis B vaccine. An interventional, descriptive study has been conducted on children who had been immunized with Cuban recombinant Hepatitis B vaccine and their antibody titers were <10mIU/ml (nonresponder) and 10-100mIU/ml (hyporesponder) administered booster dose of the same vaccine in their Deltoid muscles. The response of 141 children with the mean age of 1.9 years to booster dose of vaccine were 94.3% and 100% vaccines with the first and second booster dose of vaccination respectively. The anti-HBs titer in nonresponders and hyporesponders were 468+-346 and 783+-346mIU/ml respectively with significant differences between two groups (P=0.001). This study demonstrate moderately increase antibody production in the majority of vaccines with single supplementary vaccine. (author)

  14. Single shot of 17D vaccine may not confer life-long protection against yellow fever.

    Science.gov (United States)

    Vasconcelos, Pedro Fc

    2018-02-01

    The yellow fever (YF) vaccine has been used since the 1930s to prevent YF, which is a severe infectious disease caused by the yellow fever virus (YFV), and mainly transmitted by Culicidae mosquitoes from the genera Aedes and Haemagogus . Until 2013, the World Health Organization (WHO) recommended the administration of a vaccine dose every ten years. A new recommendation of a single vaccine dose to confer life-long protection against YFV infection has since been established. Recent evidence published elsewhere suggests that at least a second dose is needed to fully protect against YF disease. Here, we discuss the feasibility of administering multiple doses, the necessity for a new and modern vaccine, and recommend that the WHO conveys a meeting to discuss YFV vaccination strategies for people living in or travelling to endemic areas.

  15. Effect of Vaccination on Transmission of HPAI H5N1: The Effect of a Single Vaccination Dose on Transmission of Highly Pathogenic Avian Influanza H5N1 in Peking Ducks

    NARCIS (Netherlands)

    Goot, van der J.A.; Boven, van R.M.; Jong, de M.C.M.; Koch, G.

    2007-01-01

    The highly pathogenic H5N1 avian influenza virus is widespread among domestic ducks throughout Southeast Asia. Many aspects of the poultry industry and social habits hinder the containment and eradication of AI. Vaccination is often put forward as a tool for the control of AI. However, vaccination

  16. Single-cycle adenovirus vectors in the current vaccine landscape.

    Science.gov (United States)

    Barry, Michael

    2018-02-01

    Traditional inactivated and protein vaccines generate strong antibodies, but struggle to generate T cell responses. Attenuated pathogen vaccines generate both, but risk causing the disease they aim to prevent. Newer gene-based vaccines drive both responses and avoid the risk of infection. While these replication-defective (RD) vaccines work well in small animals, they can be weak in humans because they do not replicate antigen genes like more potent replication-competent (RC) vaccines. RC vaccines generate substantially stronger immune responses, but also risk causing their own infections. To circumvent these problems, we developed single-cycle adenovirus (SC-Ad) vectors that amplify vaccine genes, but that avoid the risk of infection. This review will discuss these vectors and their prospects for use as vaccines. Areas covered: This review provides a background of different types of vaccines. The benefits of gene-based vaccines and their ability to replicate antigen genes are described. Adenovirus vectors are discussed and compared to other vaccine types. Replication-defective, single-cycle, and replication-competent Ad vaccines are compared. Expert commentary: The potential utility of these vaccines are discussed when used against infectious diseases and as cancer vaccines. We propose a move away from replication-defective vaccines towards more robust replication-competent or single-cycle vaccines.

  17. Use of a booster dose of capsular group C meningococcal glycoconjugate vaccine to demonstrate immunologic memory in children primed with one or two vaccine doses in infancy.

    Science.gov (United States)

    Pace, David; Khatami, Ameneh; Attard-Montalto, Simon; Voysey, Merryn; Finn, Adam; Faust, Saul N; Heath, Paul T; Borrow, Ray; Snape, Matthew D; Pollard, Andrew J

    2016-12-07

    Use of a polysaccharide vaccine challenge to demonstrate immunologic memory after priming with capsular group C meningococcal conjugate vaccines (MenCC) risks induction of immunologic hyporesponsiveness. For this reason, MenCC vaccines are now used as probes of immunologic memory, however, no studies have demonstrated their ability to distinguish primed from unprimed children. This study was part of a randomised controlled trial investigating the immunogenicity of a booster dose of the combined Haemophilus influenzae type b and MenC-tetanus toxoid vaccine (Hib-MenC-TT) in infants receiving reduced dose MenCC vaccine priming schedules (one MenC-CRM/MenC-TT or two MenC-CRM vaccine doses) compared with an unprimed group. Antibody kinetics were studied in a subset of 269 children by measuring changes in the MenC serum bactericidal antibody, using rabbit complement, (MenC rSBA) titres and MenC specific IgG memory B-cells before and at 6 and 28days following the 12month booster vaccination. At 6days after the 12monthMenCC vaccine, the rise in MenC rSBA titres and MenC specific IgG memory B-cells of the primed groups were significantly higher than the infant MenCC naïve group. Participants primed with one MenC-TT dose had the highest increase in MenC rSBA titres compared with all other groups. The MenC rSBA titres at the 28th compared with the 6th day after boosting was significantly higher in those primed with a single MenC-TT/MenC-CRM vaccine in infancy compared with those who were not primed or who were primed with two doses of the MenC-CRM vaccine. Immunologic memory can be demonstrated by a MenCC booster vaccination but is affected by the type and number of MenCC doses used for infant priming. The MenC rSBA responses can be used to demonstrate successful immunologic priming. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis

    Science.gov (United States)

    Joseph, SK; Ramaswamy, K

    2013-01-01

    The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to the vaccinated host. This hypothesis was tested using single dose of DNA and Protein or Protein alone of the BmHAT vaccination in gerbils followed by live trickle L3 infection as booster dose. Vaccine-induced protection in gerbils was determined by worm establishment, micropore chamber assay and by antibody dependant cell cytotoxicity (ADCC) assay. Results were compared with the traditional prime-boost vaccination regimen. Gerbils vaccinated with BmHAT and boosted with L3 trickle infection were protected 51% (BmHAT DNA-Protein) and 48% (BmHAT Protein) respectively. BmHAT vaccination plus L3 trickle booster generated significant titer of antigen-specific IgG antibodies comparable to the traditional prime boost vaccination approach. BmHAT vaccination plus L3 trickle booster also generated antigen-specific cells in the spleen of vaccinated animals and these cells secreted predominantly IFN-γ and IL-4 in response to the vaccine antigens. These studies thus show that single dose of BmHAT multivalent vaccination followed by L3 trickle booster infection can confer significant protection against lymphatic filariasis. PMID:23735679

  19. Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis.

    Science.gov (United States)

    Joseph, S K; Ramaswamy, K

    2013-07-18

    The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to the vaccinated host. This hypothesis was tested using single dose of DNA and protein or protein alone of the BmHAT vaccination in gerbils followed by live trickle L3 infection as booster dose. Vaccine-induced protection in gerbils was determined by worm establishment, micropore chamber assay and by antibody dependant cell cytotoxicity (ADCC) assay. Results were compared with the traditional prime-boost vaccination regimen. Gerbils vaccinated with BmHAT and boosted with L3 trickle infection were protected 51% (BmHAT DNA-protein) and 48% (BmHAT protein) respectively. BmHAT vaccination plus L3 trickle booster generated significant titer of antigen-specific IgG antibodies comparable to the traditional prime boost vaccination approach. BmHAT vaccination plus L3 trickle booster also generated antigen-specific cells in the spleen of vaccinated animals and these cells secreted predominantly IFN-γ and IL-4 in response to the vaccine antigens. These studies thus show that single dose of BmHAT multivalent vaccination followed by L3 trickle booster infection can confer significant protection against lymphatic filariasis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Vaccination of piglets up to 1 week of age with a single-dose Mycoplasma hyopneumoniae vaccine induces protective immunity within 2 weeks against virulent challenge in the presence of maternally derived antibodies.

    Science.gov (United States)

    Wilson, Stephen; Van Brussel, Leen; Saunders, Gillian; Runnels, Paul; Taylor, Lucas; Fredrickson, Dan; Salt, Jeremy

    2013-05-01

    Enzootic pneumonia, resulting from infection with Mycoplasma hyopneumoniae, is of considerable economic importance to the pig industry and normally is controlled through active vaccination of piglets. We have demonstrated that administration of an inactivated Mycoplasma hyopneumoniae vaccine to piglets less than 1 week old is efficacious under field conditions and reduces the level of lung lesions observed in comparison to that in control pigs. Here, the results of two separate studies, one in piglets with and the second one in piglets without maternal antibodies, conducted to satisfy the requirements of the European Pharmacopoeia (monograph no. 07/2009:2448), are reported. Piglets received either minimal titer Suvaxyn MH-One or saline at less than 1 week of age and were challenged with Mycoplasma hyopneumoniae 2 weeks later. The number of lung lesions was recorded 4 weeks after challenge, and bronchial swab and lung tissue specimens were analyzed for quantification of Mycoplasma hyopneumoniae DNA. In the presence and absence of maternal antibodies, vaccination of piglets at less than 1 week of age was efficacious, with vaccinated piglets having significantly lower percentages of lung with lesions and lower Mycoplasma hyopneumoniae counts detected in bronchial swab and lung tissue specimens at necropsy. In conclusion, the vaccination of piglets at 1 week of age with Suvaxyn MH-One is efficacious in the presence of high levels of maternal antibodies.

  1. The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study.

    Directory of Open Access Journals (Sweden)

    Andrew S Azman

    2015-08-01

    Full Text Available In 2013, a stockpile of oral cholera vaccine (OCV was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both.Using mathematical models we determined the minimum relative single-dose efficacy (MRSE at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%-56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%. This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%-88% for two doses and 44% (95% CI -27% to 76% for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%-88%, which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943-86,205 cases in Zimbabwe, 78,317 (95% PI 57,435-100,150 in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490-3,170 cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect

  2. Budget constraint and vaccine dosing: A mathematical modelling exercise

    NARCIS (Netherlands)

    Standaert, Baudouin A.; Curran, Desmond; Postma, Maarten J.

    2014-01-01

    Background: Increasing the number of vaccine doses may potentially improve overall efficacy. Decision-makers need information about choosing the most efficient dose schedule to maximise the total health gain of a population when operating under a constrained budget. The objective of this study is to

  3. The administration of a single dose of a multivalent (DHPPiL4R vaccine prevents clinical signs and mortality following virulent challenge with canine distemper virus, canine adenovirus or canine parvovirus

    Directory of Open Access Journals (Sweden)

    Stephen Wilson

    2014-01-01

    In conclusion, we demonstrated that a single administration of a minimum titre, multivalent vaccine to dogs of six weeks of age is efficacious and prevents clinical signs and mortality caused by CAV-1 and CDV; prevents clinical signs and significantly reduces virus shedding caused by CAV-2; and prevents clinical signs, leucopoenia and viral excretion caused by CPV.

  4. Response to booster doses of hepatitis B vaccine among young adults who had received neonatal vaccination.

    Directory of Open Access Journals (Sweden)

    Paul K S Chan

    Full Text Available Newborns who have received hepatitis B immunization in 1980s are now young adults joining healthcare disciplines. The need for booster, pre- and post-booster checks becomes a practical question.The aim of this study is to refine the HBV vaccination policy for newly admitted students in the future.A prospective study on medical and nursing school entrants to evaluate hepatitis B serostatus and the response to booster doses among young adults.Among 212 students, 17-23-year-old, born after adoption of neonatal immunization, 2 (0.9% were HBsAg positive, 40 (18.9% were anti-HBs positive. At 1 month after a single-dose booster for anti-HBs-negative students, 14.5% had anti-HBs 100 mIU/mL, respectively. The anti-HBs levels were significantly higher for females than males (mean [SD]: 431 [418] vs. 246 [339] mIU/mL, P = 0.047. At 2-4 month after the third booster dose, 97.1% had anti-HBs >100 mIU/mL and 2.9% had 10-100 mIU/mL.Pre-booster check is still worthwhile to identify carriers among newly recruited healthcare workers born after adoption of neonatal immunization. A 3-dose booster, rather than a single dose, is required for the majority to achieve an anti-HBs level >100 mIU/mL, as memory immunity has declined in a substantial proportion of individuals. Cost-effectiveness of post-booster check for anti-HBs is low and should be further evaluated based on contextual specific utilization of results.

  5. Persistence of immune responses after a single dose of Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo®) or Menactra® among healthy adolescents.

    Science.gov (United States)

    Gill, Christopher J; Baxter, Roger; Anemona, Alessandra; Ciavarro, Giuseppe; Dull, Peter

    2010-11-01

    The persistence of human bactericidal activity (hSBA) responses in adolescents was assessed 22 months after vaccination with one dose of Menveo® (MenACWY-CRM; Novartis) or Menactra® (MCV4) (sanofi pasteur). The proportion of subjects with hSBA titers ≥8 was significantly higher among recipients of MenACWY-CRM than MCV4 for serogroups A, W-135 and Y.

  6. Fluzone High-Dose Seasonal Influenza Vaccine

    Science.gov (United States)

    ... Prevent Flu Good Health Habits Cover Your Cough Home, Work & School Prevention Vaccine Benefits Symptoms & Diagnosis Flu Symptoms & ... result was 9.7% to 36.5%. A separate study published in The Lancet ... 38,000 residents of 823 nursing homes in 38 states during the 2013-14 flu ...

  7. Efficacy of a single oral dose of a live bivalent E. coli vaccine against post-weaning diarrhea due to F4 and F18-positive enterotoxigenic E. coli.

    Science.gov (United States)

    Nadeau, É; Fairbrother, J M; Zentek, J; Bélanger, L; Tremblay, D; Tremblay, C-L; Röhe, I; Vahjen, W; Brunelle, M; Hellmann, K; Cvejić, D; Brunner, B; Schneider, C; Bauer, K; Wolf, R; Hidalgo, Á

    2017-08-01

    F4- and F18-positive enterotoxigenic E. coli strains (F4-ETEC and F18-ETEC) are important causes of post-weaning diarrhea (PWD) in pigs. F4 (antigenic variant ac) and F18 (ab and ac) fimbriae are major antigens that play an important role in the early stages of infection. Herein, the efficacy of a live oral vaccine consisting of two non-pathogenic E. coli strains, one F4ac- and one F18ac-positive, was evaluated using F4ac-ETEC and F18ab-ETEC challenge models. A randomized, masked, placebo-controlled, block design, parallel-group confirmatory study with two different vaccination-challenge intervals (7 and 21 days) was conducted for each challenge model. The vaccine was administered in one dose, to ≥18-day-old piglets via drinking water. Efficacy was assessed by evaluating diarrhea, clinical observations, weight gain and fecal shedding of F4-ETEC or F18-ETEC. Anti-F4 and anti-F18 immunoglobulins in blood were measured. The vaccination resulted in significant reductions in clinical PWD and fecal shedding of F4-ETEC and F18-ETEC after the 7- and 21-day-post-vaccination heterologous challenges, except for after the 21-day-post-vaccination F4-ETEC challenge, when the clinical PWD was too mild to demonstrate efficacy. A significant reduction of mortality and weight loss by vaccination were observed following the F18-ETEC challenge. The 7-day protection was associated with induction of anti-F4 and anti-F18 IgM, whereas the 21-day protection was mainly associated with anti-F4 and anti-F18 IgA. The 7-day onset and 21-day duration of protection induced by this vaccine administered once in drinking water to pigs of at least 18days of age were confirmed by protection against F4-ETEC and F18-ETEC, and induction of F4 and F18-specific immunity. Cross protection of the vaccine against F18ab-E. coli was demonstrated for both the 7- and 21-day F18-ETEC challenges. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Potential Impact of Accelerating the Primary Dose of Rotavirus Vaccine in Infants

    OpenAIRE

    Halvorson, Elizabeth E.; Peters, Timothy R.; Snively, Beverly M.; Poehling, Katherine A.

    2012-01-01

    We estimated the potential impact of administering the first dose of rotavirus vaccine at 6 weeks (42 days of life) instead of 2 months of age, which is permissible for all U.S. vaccines recommended at 2 months of age, on rotavirus hospitalization rates. We used published data for hospitalization rates, vaccine coverage, and vaccine efficacy after one dose and assumed a two-week delay in seroconversion after vaccine administration in the United States. Administering the first dose of rotaviru...

  9. Vial usage, device dead space, vaccine wastage, and dose accuracy of intradermal delivery devices for inactivated poliovirus vaccine (IPV).

    Science.gov (United States)

    Jarrahian, Courtney; Rein-Weston, Annie; Saxon, Gene; Creelman, Ben; Kachmarik, Greg; Anand, Abhijeet; Zehrung, Darin

    2017-03-27

    Intradermal delivery of a fractional dose of inactivated poliovirus vaccine (IPV) offers potential benefits compared to intramuscular (IM) delivery, including possible cost reductions and easing of IPV supply shortages. Objectives of this study were to assess intradermal delivery devices for dead space, wastage generated by the filling process, dose accuracy, and total number of doses that can be delivered per vial. Devices tested included syringes with staked (fixed) needles (autodisable syringes and syringes used with intradermal adapters), a luer-slip needle and syringe, a mini-needle syringe, a hollow microneedle device, and disposable-syringe jet injectors with their associated filling adapters. Each device was used to withdraw 0.1-mL fractional doses from single-dose IM glass vials which were then ejected into a beaker. Both vial and device were weighed before and after filling and again after expulsion of liquid to record change in volume at each stage of the process. Data were used to calculate the number of doses that could potentially be obtained from multidose vials. Results show wide variability in dead space, dose accuracy, overall wastage, and total number of doses that can be obtained per vial among intradermal delivery devices. Syringes with staked needles had relatively low dead space and low overall wastage, and could achieve a greater number of doses per vial compared to syringes with a detachable luer-slip needle. Of the disposable-syringe jet injectors tested, one was comparable to syringes with staked needles. If intradermal delivery of IPV is introduced, selection of an intradermal delivery device can have a substantial impact on vaccine wasted during administration, and thus on the required quantity of vaccine that needs to be purchased. An ideal intradermal delivery device should be not only safe, reliable, accurate, and acceptable to users and vaccine recipients, but should also have low dead space, high dose accuracy, and low overall

  10. A single or multistage mycobacterium avium subsp. paratuberculosis subunit vaccine

    DEFF Research Database (Denmark)

    2014-01-01

    The present invention provides one or more immunogenic polypeptides for use in a preventive or therapeutic vaccine against latent or active infection in a human or animal caused by a Mycobacterium species, e.g. Mycobacterium avium subsp. paratuberculosis. Furthermore a single or multi-phase vaccine...... comprising the one or more immunogenic polypeptides is provided for administration for the prevention or treatment of infection with a Mycobacterium species, e.g. Mycobacterium avium subsp. paratuberculosis. Additionally, nucleic acid vaccines, capable of in vivo expression of the multi-phase vaccine...

  11. Single-dose ceftriaxone for chancroid.

    Science.gov (United States)

    Bowmer, M I; Nsanze, H; D'Costa, L J; Dylewski, J; Fransen, L; Piot, P; Ronald, A R

    1987-01-01

    Men with genital ulcers that were culture positive for Haemophilus ducreyi were treated with intramuscular ceftriaxone and randomized to three different dose regimens. All but 1 of 50 men treated with 1 g of intramuscular ceftriaxone were cured. Similarly, 0.5 and 0.25 g cured 43 of 44 men and 37 of 38 men, respectively. A single dose of 250 mg of intramuscular ceftriaxone is an effective treatment for chancroid. PMID:3566241

  12. The impact of assumptions regarding vaccine-induced immunity on the public health and cost-effectiveness of hepatitis A vaccination: Is one dose sufficient?

    Science.gov (United States)

    Curran, Desmond; de Ridder, Marc; Van Effelterre, Thierry

    2016-01-01

    ABSTRACT Hepatitis A vaccination stimulates memory cells to produce an anamnestic response. In this study, we used a mathematical model to examine how long-term immune memory might convey additional protection against clinical/icteric infections. Dynamic and decision models were used to estimate the expected number of cases, and the costs and quality-adjusted life-years (QALYs), respectively. Several scenarios were explored by assuming: (1) varying duration of vaccine-induced immune memory, (2) and/or varying levels of vaccine-induced immune memory protection (IMP), (3) and/or varying levels of infectiousness in vaccinated individuals with IMP. The base case analysis assumed a time horizon of 25 y (2012 – 2036), with additional analyses over 50 and 75 y. The analyses were conducted in the Mexican public health system perspective. In the base case that assumed no vaccine-induced IMP, the 2-dose hepatitis A vaccination strategy was cost-effective compared with the 1-dose strategy over the 3 time horizons. However, it was not cost-effective if we assumed additional IMP durations of at least 10 y in the 25-y horizon. In the 50- and 75-y horizons, the 2-dose strategy was always cost-effective, except when 100% reduction in the probability of icteric Infections, 75% reduction in infectiousness, and mean durations of IMP of at least 50 y were assumed. This analysis indicates that routine vaccination of toddlers against hepatitis A virus would be cost-effective in Mexico using a single-dose vaccination strategy. However, the cost-effectiveness of a second dose depends on the assumptions of additional protection by IMP and the time horizon over which the analysis is performed. PMID:27428611

  13. Fractional-Dose Inactivated Poliovirus Vaccine Campaign - Sindh Province, Pakistan, 2016.

    Science.gov (United States)

    Pervaiz, Aslam; Mbaeyi, Chukwuma; Baig, Mirza Amir; Burman, Ashley; Ahmed, Jamal A; Akter, Sharifa; Jatoi, Fayaz A; Mahamud, Abdirahman; Asghar, Rana Jawad; Azam, Naila; Shah, Muhammad Nadeem; Laghari, Mumtaz Ali; Soomro, Kamaluddin; Wadood, Mufti Zubair; Ehrhardt, Derek; Safdar, Rana M; Farag, Noha

    2017-12-01

    Following the declaration of eradication of wild poliovirus (WPV) type 2 in September 2015, trivalent oral poliovirus vaccine (tOPV) was withdrawn globally to reduce the risk for type 2 vaccine-derived poliovirus (VDPV2) transmission; all countries implemented a synchronized switch to bivalent OPV (type 1 and 3) in April 2016 (1,2). Any isolation of VDPV2 after the switch is to be treated as a potential public health emergency and might indicate the need for supplementary immunization activities (3,4). On August 9, 2016, VDPV2 was isolated from a sewage sample taken from an environmental surveillance site in Hyderabad, Sindh province, Pakistan. Possible vaccination activities in response to VDPV2 isolation include the use of injectable inactivated polio vaccine (IPV), which poses no risk for vaccine-derived poliovirus transmission. Fractional-dose, intradermal IPV (fIPV), one fifth of the standard intramuscular dose, has been developed to more efficiently manage limited IPV supplies. fIPV has been shown in some studies to be noninferior to full-dose IPV (5,6) and was used successfully in response to a similar detection of a single VDPV2 isolate from sewage in India (7). Injectable fIPV was used for response activities in Hyderabad and three neighboring districts. This report describes the findings of an assessment of preparatory activities and subsequent implementation of the fIPV campaign. Despite achieving high coverage (>80%), several operational challenges were noted. The lessons learned from this campaign could help to guide the planning and implementation of future fIPV vaccination activities.

  14. Dose-Related Differences in Effectiveness of Human Papillomavirus Vaccination Against Genital Warts

    DEFF Research Database (Denmark)

    Blomberg, Maria; Dehlendorff, Christian; Sand, Carsten

    2015-01-01

    BACKGROUND: Reducing the number of doses in the human papillomavirus (HPV) vaccination regimen from 3 to 2 could increase coverage rates. In this cohort study, we assessed the risk of genital warts (GWs) according to timing and number of doses of quadrivalent HPV vaccine. METHODS: From population......-based registries, we identified all girls in Denmark born during 1985-1999, for whom information on HPV vaccinations was retrieved. The cohort was followed for GW occurrence during 2006-2012. Incidence rate ratios (IRRs) were calculated by Poisson regression to determine differences in GW rates by number...... of vaccine doses. RESULTS: Of the 550,690 girls in the cohort, 361 734 had been vaccinated. Of these, 25.9% had been vaccinated twice and 58.8% 3 times. The risk of GWs decreased significantly with each additional dose of vaccine. For girls who received 2 doses, extension of the interval between doses...

  15. The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

    Science.gov (United States)

    Azman, Andrew S.; Luquero, Francisco J.; Ciglenecki, Iza; Grais, Rebecca F.; Sack, David A.; Lessler, Justin

    2015-01-01

    Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%–56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%–88%) for two doses and 44% (95% CI −27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%–88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943–86,205) cases in Zimbabwe, 78,317 (95% PI 57,435–100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490–3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture

  16. [The reactogenicity of Heberbiovac-HB vaccine at different doses].

    Science.gov (United States)

    Díaz González, M; Navia Molina, O; Bravo González, J R; Pedroso Flaquet, P; Urbino López, A

    1995-01-01

    Reactogenicity was measured after applying the Heberbiovac-HB recombinant vaccine against hepatitis B virus to three groups of children aged 6-9 years. The vaccine was derived from yeast cells, administered at doses of 10, 5, and 2.5 g, with a schedule of 0, 1 and 6 months. The overall observed symptomatology was low (12.2%) in the three groups with 10.7%, 13.5%, and 12.3% for 10, 5, and 2.5 g, respectively. The predominant symptoms and signs were febricula (7.0%), local pain (3.1%), and erythema (1.2%). No significant differences were found when making a comparison between groups and sexes. An acceptable reactogenicity of the immunogen was confirmed, thus its use is recommended for the protection against hepatitis B virus.

  17. Cost-effectiveness of HPV vaccination regime: comparing twice versus thrice vaccinations dose regime among adolescent girls in Malaysia.

    Science.gov (United States)

    Aljunid, Syed; Maimaiti, Namaitijiang; Nur, Amrizal M; Noor, Mohd Rushdan Md; Wan Puteh, Sharifa Ezat

    2016-01-23

    The HPV vaccine was introduced to Malaysian national immunization programme in 2010. The current implementation age of HPV vaccination in Malaysian is at the age of 13 years school girls, given according to a 3 doses protocol which may complicate implementation and compliance. Aim of the study is to determine the cost-effectiveness of HPV vaccination regime comparing twice versus thrice HPV vaccinations dose regime among adolescent girls in Malaysia. A Markov cohort model reflecting the natural history of HPV infection accounting for oncogenic and low-risk HPV was adapted for 13 year old Malaysian girls cohort (n = 274,050). Transition probabilities, utilities values, epidemiological and cost data were sourced from published literature and local data. Vaccine effectiveness was based on overall efficacy reported from 3-doses clinical trials, with the assumption that the 2-doses is non-inferior to the 3-doses allowing overall efficacy to be inferred from the 3-doses immunogenicity data. Price parity and life-long protection were assumed. The payer perspective was adopted, with appropriate discounting for costs (3 %) and outcomes (3 %). One way sensitivity analysis was conducted. The sensitivity analysis on cost of vaccine, vaccine coverage and discount rate with a 2-doses protocol was performed. The 3-doses and 2-doses regimes showed same number of Cervical Cancers averted (361 cases); QALYs saved at 7,732,266. However, the lifetime protection under the 2-doses regime, showed a significant cost-savings of RM 36, 722,700 compared to the 3-doses scheme. The MOH Malaysia could vaccinate 137,025 more girls in this country using saving 2-doses regime vaccination programme. The model predicted that 2-doses HPV vaccination schemes can avoid additional 180 Cervical Cancers and 63 deaths compare to 3-doses. A 2-doses HPV vaccination scheme may enable Malaysian women to be protected at a lower cost than that achievable under a 3-doses scheme, while avoiding the same number of

  18. Persistence of Meningococcal Antibodies and Response to a Third Dose After a Two-dose Vaccination Series with Investigational MenABCWY Vaccine Formulations in Adolescents.

    Science.gov (United States)

    Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Han, Linda; Smolenov, Igor; Dull, Peter

    2015-10-01

    In a primary study, healthy adolescents received 2 doses (months 0/2) of 1 of the 4 investigational meningococcal ABCWY vaccine formulations, containing components of licensed quadrivalent glycoconjugate vaccine MenACWY-CRM, combined with different amounts of recombinant proteins (rMenB) and outer membrane vesicles (OMV) from a licensed serogroup B vaccine, or 2 doses of rMenB alone or 1 dose of MenACWY-CRM then a placebo. This phase 2 extension study evaluated antibody persistence up to 10 months after the 2-dose series and the immunogenicity and safety of a third dose (month 6). Immune responses against serogroups ACWY and serogroup B test strains were measured by serum bactericidal assay with human complement. At month 12, antibody persistence against serogroups ACWY in all 2-dose MenABCWY groups was at least comparable with the 1-dose MenACWY-CRM group. Bactericidal antibodies against most serogroup B test strains declined by month 6, then plateaued over the subsequent 6 months, with overall higher antibody persistence associated with OMV-containing formulations. A third MenABCWY vaccine dose induced robust immune responses against vaccine antigens, although antibody levels 6 months later were comparable with those observed 5 months after the 2-dose series. All investigational MenABCWY vaccines were well tolerated. Two or three doses of investigational MenABCWY vaccines elicited immune responses against serogroups ACWY that were at least comparable with those after 1 dose of MenACWY-CRM. After either vaccination series, investigational MenABCWY vaccine formulations containing OMV had the highest immunogenicity against most serogroup B test strains. No safety concerns were identified in this study.

  19. An assessment of mumps vaccine effectiveness by dose during an outbreak in Canada.

    Science.gov (United States)

    Deeks, Shelley L; Lim, Gillian H; Simpson, Mary Anne; Gagné, Louise; Gubbay, Jonathan; Kristjanson, Erik; Fung, Cecilia; Crowcroft, Natasha S

    2011-06-14

    This investigation was done to assess vaccine effectiveness of one and two doses of the measles, mumps and rubella (MMR) vaccine during an outbreak of mumps in Ontario. The level of coverage required to reach herd immunity and interrupt community transmission of mumps was also estimated. Information on confirmed cases of mumps was retrieved from Ontario's integrated Public Health Information System. Cases that occurred between Sept. 1, 2009, and June 10, 2010, were included. Selected health units supplied coverage data from the Ontario Immunization Record Information System. Vaccine effectiveness by dose was calculated using the screening method. The basic reproductive number (R(0)) represents the average number of new infections per case in a fully susceptible population, and R(0) values of between 4 and 10 were considered for varying levels of vaccine effectiveness. A total of 134 confirmed cases of mumps were identified. Information on receipt of MMR vaccine was available for 114 (85.1%) cases, of whom 63 (55.3%) reported having received only one dose of vaccine; 32 (28.1%) reported having received two doses. Vaccine effectiveness of one dose of the MMR vaccine ranged from 49.2% to 81.6%, whereas vaccine effectiveness of two doses ranged from 66.3% to 88.0%. If we assume vaccine effectiveness of 85% for two doses of the vaccine, vaccine coverage of 88.2% and 98.0% would be needed to interrupt community transmission of mumps if the corresponding reproductive values were four and six. Our estimates of vaccine effectiveness of one and two doses of mumps-containing vaccine were consistent with the estimates that have been reported in other outbreaks. Outbreaks occurring in Ontario and elsewhere serve as a warning against complacency over vaccination programs.

  20. Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study.

    Science.gov (United States)

    Azman, Andrew S; Parker, Lucy A; Rumunu, John; Tadesse, Fisseha; Grandesso, Francesco; Deng, Lul L; Lino, Richard Laku; Bior, Bior K; Lasuba, Michael; Page, Anne-Laure; Ontweka, Lameck; Llosa, Augusto E; Cohuet, Sandra; Pezzoli, Lorenzo; Sodjinou, Dossou Vincent; Abubakar, Abdinasir; Debes, Amanda K; Mpairwe, Allan M; Wamala, Joseph F; Jamet, Christine; Lessler, Justin; Sack, David A; Quilici, Marie-Laure; Ciglenecki, Iza; Luquero, Francisco J

    2016-11-01

    Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention. We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India). Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0). One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological

  1. Optimization of inactivated H5N9 highly pathogenic avian influenza vaccine and inactivated Salmonella enterica serovar Typhimurium vaccine with antigen dose and prime-boost regimen in domestic ducks.

    Science.gov (United States)

    Yuk, Seong-Su; To, Eredene-Ochir; Kwon, Jung-Hoon; Noh, Jin-Yong; Hong, Woo-Tack; Jeong, Jei-Hyun; Gwon, Gyeong-Bin; Song, Chang-Seon

    2017-09-01

    Owing to the increase in the number of diseases affecting ducks and the demand for food safety by consumers, vaccination has become one of the factors that influence duck meat productivity. The highly pathogenic avian influenza (HPAI) virus is one of the most prevalent and causes one of the most lethal diseases in domestic ducks, and Salmonella enterica serovar Typhimurium is a food-borne pathogen persistent in the domestic duck population. To better understand the optimal usage of HPAI and S. enterica serovar Typhimurium vaccines, we aimed to determine antigen dose, oil and gel adjuvant usage with prime-boost regimen, and vaccination age, inducing the best immune response in ducks, without an effect on body weight gain. In the case of the inactivated H5N9 vaccine, a single dose of vaccine was inadequate to induce proper antibody titer when administered to day-old ducks, which necessitates boost vaccination. Administration of the oil-adjuvanted H5N9 vaccine administration in day-old and 2-week-old ducks resulted in a lower body weight at the time of slaughtering, compared to that of gel-adjuvanted H5N9 vaccine. However, gel-adjuvanted H5N9 vaccine failed to induce proper immune response to an extent recommend by OIE-World Organization for Animal Health. In the case of the Salmonella enterica serovar Typhimurium vaccine, a moderate or low dose of vaccine was appropriate for day-old ducks receiving the gel prime-oil boost vaccination. Single vaccination with oil adjuvants affects the mean body weight of 7-week-old ducks, suggesting that the gel adjuvant is more suitable for meat production. We expect that the use of adjuvants in a prime-boost regimen and at antigen doses set in this study will be helpful to maximize body weight in the case of domestic duck production at the actual farm site. © 2017 Poultry Science Association Inc.

  2. Comparison of two dose and three dose human papillomavirus vaccine schedules: cost effectiveness analysis based on transmission model.

    Science.gov (United States)

    Jit, Mark; Brisson, Marc; Laprise, Jean-François; Choi, Yoon Hong

    2015-01-06

    To investigate the incremental cost effectiveness of two dose human papillomavirus vaccination and of additionally giving a third dose. Cost effectiveness study based on a transmission dynamic model of human papillomavirus vaccination. Two dose schedules for bivalent or quadrivalent human papillomavirus vaccines were assumed to provide 10, 20, or 30 years' vaccine type protection and cross protection or lifelong vaccine type protection without cross protection. Three dose schedules were assumed to give lifelong vaccine type and cross protection. United Kingdom. Males and females aged 12-74 years. No, two, or three doses of human papillomavirus vaccine given routinely to 12 year old girls, with an initial catch-up campaign to 18 years. Costs (from the healthcare provider's perspective), health related utilities, and incremental cost effectiveness ratios. Giving at least two doses of vaccine seems to be highly cost effective across the entire range of scenarios considered at the quadrivalent vaccine list price of £86.50 (€109.23; $136.00) per dose. If two doses give only 10 years' protection but adding a third dose extends this to lifetime protection, then the third dose also seems to be cost effective at £86.50 per dose (median incremental cost effectiveness ratio £17,000, interquartile range £11,700-£25,800). If two doses protect for more than 20 years, then the third dose will have to be priced substantially lower (median threshold price £31, interquartile range £28-£35) to be cost effective. Results are similar for a bivalent vaccine priced at £80.50 per dose and when the same scenarios are explored by parameterising a Canadian model (HPV-ADVISE) with economic data from the United Kingdom. Two dose human papillomavirus vaccine schedules are likely to be the most cost effective option provided protection lasts for at least 20 years. As the precise duration of two dose schedules may not be known for decades, cohorts given two doses should be closely

  3. Dose optimisation in single plane interstitial brachytherapy

    DEFF Research Database (Denmark)

    Tanderup, Kari; Hellebust, Taran Paulsen; Honoré, Henriette Benedicte

    2006-01-01

    patients,       treated for recurrent rectal and cervical cancer, flexible catheters were       sutured intra-operatively to the tumour bed in areas with compromised       surgical margin. Both non-optimised, geometrically and graphically       optimised CT -based dose plans were made. The overdose index...... on the       regularity of the implant, such that the benefit of optimisation was       larger for irregular implants. OI and HI correlated strongly with target       volume limiting the usability of these parameters for comparison of dose       plans between patients. CONCLUSIONS: Dwell time optimisation significantly......BACKGROUND AND PURPOSE: Brachytherapy dose distributions can be optimised       by modulation of source dwell times. In this study dose optimisation in       single planar interstitial implants was evaluated in order to quantify the       potential benefit in patients. MATERIAL AND METHODS: In 14...

  4. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    Directory of Open Access Journals (Sweden)

    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  5. High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against Tuberculosis.

    Science.gov (United States)

    Billeskov, Rolf; Lindenstrøm, Thomas; Woodworth, Joshua; Vilaplana, Cristina; Cardona, Pere-Joan; Cassidy, Joseph P; Mortensen, Rasmus; Agger, Else Marie; Andersen, Peter

    2017-01-01

    Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world's population with latent Mtb infection (LTBI), and 5-10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection.

  6. High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against Tuberculosis

    Directory of Open Access Journals (Sweden)

    Rolf Billeskov

    2018-01-01

    Full Text Available Mycobacterium tuberculosis (Mtb, the etiologic agent of tuberculosis (TB, causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world’s population with latent Mtb infection (LTBI, and 5–10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660 TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection.

  7. Single toxin dose-response models revisited

    Energy Technology Data Exchange (ETDEWEB)

    Demidenko, Eugene, E-mail: eugened@dartmouth.edu [Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH03756 (United States); Glaholt, SP, E-mail: sglaholt@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States); Kyker-Snowman, E, E-mail: ek2002@wildcats.unh.edu [Department of Natural Resources and the Environment, University of New Hampshire, Durham, NH03824 (United States); Shaw, JR, E-mail: joeshaw@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Chen, CY, E-mail: Celia.Y.Chen@dartmouth.edu [Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States)

    2017-01-01

    The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the four models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.

  8. Fractional dosing of yellow fever vaccine to extend supply: a modelling study.

    Science.gov (United States)

    Wu, Joseph T; Peak, Corey M; Leung, Gabriel M; Lipsitch, Marc

    2016-12-10

    The ongoing yellow fever epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa, Democratic Republic of the Congo, in July-August, 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidation of the conditions under which dose fractionation would reduce transmission. We estimate the effective reproductive number for yellow fever in Angola using disease natural history and case report data. With simple mathematical models of yellow fever transmission, we calculate the infection attack rate (the proportion of population infected over the course of an epidemic) with various levels of transmissibility and 5-fold fractional-dose vaccine efficacy for two vaccination scenarios, ie, random vaccination in a hypothetical population that is completely susceptible, and the Kinshasa vaccination campaign in July-August, 2016, with different age cutoff for fractional-dose vaccines. We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (ie, a proportion of vaccine recipients receive complete protection [VE] and the remainder receive no protection), n-fold fractionation can greatly reduce infection attack rate as long as VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (ie, the susceptibility of each vaccine recipient is reduced by a factor that is equal to the vaccine efficacy). The age cutoff for fractional-dose vaccines chosen by WHO for the Kinshasa vaccination campaign (2 years) provides the largest reduction in infection attack rate if the efficacy of 5-fold fractional-dose vaccines exceeds 20%. Dose fractionation is an effective strategy for reduction of the infection attack rate that would be robust with a

  9. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination.

    Science.gov (United States)

    Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E

    2015-01-01

    No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral

  10. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination.

    Directory of Open Access Journals (Sweden)

    Anne Derbise

    Full Text Available No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably.The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50 caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50. Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1- Y. pestis.VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single

  11. Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine

    Directory of Open Access Journals (Sweden)

    Idis Faingezicht

    2002-10-01

    Full Text Available Objective. The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB and Haemophilus influenzae type b (Hib vaccines into routine childhood vaccination programs. The objectives of this study were to: 1 analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2 in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster. Methods. In the first part of the study (primary-vaccination stage, conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth. Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old, antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed. Results. In both primary-vaccination groups, at least 97.5% of the infants reached protective levels of antibodies (seropositivity against the antigens employed in the vaccines. The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection. Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93% of children still having

  12. Booster dose after 10 years is recommended following 17DD-YF primary vaccination.

    Science.gov (United States)

    Campi-Azevedo, Ana Carolina; Costa-Pereira, Christiane; Antonelli, Lis R; Fonseca, Cristina T; Teixeira-Carvalho, Andréa; Villela-Rezende, Gabriela; Santos, Raiany A; Batista, Maurício A; Campos, Fernanda M; Pacheco-Porto, Luiza; Melo Júnior, Otoni A; Hossell, Débora M S H; Coelho-dos-Reis, Jordana G; Peruhype-Magalhães, Vanessa; Costa-Silva, Matheus F; de Oliveira, Jaquelline G; Farias, Roberto H; Noronha, Tatiana G; Lemos, Jandira A; von Doellinger, Vanessa dos R; Simões, Marisol; de Souza, Mirian M; Malaquias, Luiz C; Persi, Harold R; Pereira, Jorge M; Martins, José A; Dornelas-Ribeiro, Marcos; Vinhas, Aline de A; Alves, Tatiane R; Maia, Maria de L; Freire, Marcos da S; Martins, Reinaldo de M; Homma, Akira; Romano, Alessandro P M; Domingues, Carla M; Tauil, Pedro L; Vasconcelos, Pedro F; Rios, Maria; Caldas, Iramaya R; Camacho, Luiz A; Martins-Filho, Olindo Assis

    2016-01-01

    A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT≥2.9Log10mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to naïve baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-α(+) and IFN-γ(+) produced by CD4(+) and CD8(+) T-cells along with increasing levels of IL-10(+)CD4(+)T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the naïve baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8(+) memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination.

  13. Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study

    Science.gov (United States)

    Peak, Corey M.; Leung, Gabriel M.

    2016-01-01

    Background The ongoing yellow fever (YF) epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa in July–August 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidating the conditions under which dose fractionation would reduce transmission. Methods We estimate the effective reproductive number for YF in Angola using disease natural history and case report data. With simple mathematical models of YF transmission, we calculate the infection attack rate (IAR, the proportion of population infected over the course of an epidemic) under varying levels of transmissibility and five-fold fractional-dose vaccine efficacy for two vaccination scenarios: (i) random vaccination in a hypothetical population that is completely susceptible; (ii) the Kinshasa vaccination campaign in July–August 2016 with different age cutoff for fractional-dose vaccines. Findings We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (i.e. a proportion VE of vaccinees receives complete and the remainder receive no protection), n-fold fractionation can dramatically reduce IAR as long as efficacy VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (i.e. the susceptibility of each vaccinee is reduced by a factor that is equal to the vaccine efficacy VE). The age cutoff for fractional-dose vaccines chosen by the WHO for the Kinshasa vaccination campaign (namely, 2 years) provides the largest reduction in IAR if the efficacy of five-fold fractional-dose vaccines exceeds 20%. Interpretation Dose fractionation is a very effective strategy for reducing infection attack rate that would be robust with a large margin for error in case

  14. Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection.

    Science.gov (United States)

    Hakim, Hana; Allison, Kim J; Van de Velde, Lee-Ann; Tang, Li; Sun, Yilun; Flynn, Patricia M; McCullers, Jonathan A

    2016-06-08

    Approaches to improve the immune response of immunocompromised patients to influenza vaccination are needed. Children and young adults (3-21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine. Eighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p=0.27 and 0.09 after dose 1 and 2, respectively). HD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Acoustic neuromas: single dose vs fractionated therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fuss, M; Debus, J; Lohr, F; Engenhart-Cabillic, R; Wannenmacher, M

    1997-07-01

    Purpose: Radiosurgical treatment (RS) of acoustic neuromas is a well established treatment. However, few data are available concerning conformal fractionated radiotherapy (FT) of this tumor entity. We evaluated treatment outcome and toxicity for both treatment modalities in 41 patients treated at our institution between 1984 and 1997. Material and Methods: All treatments were performed using a specially adapted linear accelerator and circular collimators for convergent beam RS or multi-leaf collimators (leaf thickness 1 or 3mm) for multi-field RS or fractionated treatment. 22 patients (7 male, 15 female, median age 60 years, range 20-83 years) were treated radiosurgically with single doses between 7 and 28 Gray (median 15 Gy) prescribed to the 80% isodose line. Tumor volumes ranged from 0.7 to 10.5 ccm with a median volume of 3.4 ccm. The median number of isocenters was 2 (1-4 isocenters). One patient was treated by a multi-field technique (14 isocentric irregularly shaped noncoplanar fields). 19 patients (5 male, 14 female, median age 55 years, range 20-81 years) were treated with stereotactic conformal radiotherapy. Median dose was 60 Gray with a median daily fraction size of 2 Gy and a median of 3 (1-4) irregularly shaped isocentric fields. Tumor volumes ranged from 0.7 to 32.4 ccm (median 15 ccm). Median follow-up was 30 months (7-149 months) for radiosurgical and 30 months (2-88 months) for fractionated treatment. Seven patients who underwent fractionated treatment had previously undergone neurosurgical resection on the contralateral side. One had undergone radiosurgery on the opposite side before. Results: All tumors were locally controlled. A volume reduction of more than 20% was seen in 16% after RS and 18% following FT. Typical posttherapeutic central reduction of contrast media enhancement was found in 73% following RS after a median of 8 (3-12) months and in 63% following FT after a median of 6 (1-12) months. Temporary brainstem edema was diagnosed in 4

  16. IMMUNE RESPONSES OF GOATS (SHAMI BREED TO VACCINATION WITH A FULL, REDUCED AND CONJUNCTIVAL DOSE OF BRUCEVAC (BRUCELLA MELITENSIS REV.1 VACCINE

    Directory of Open Access Journals (Sweden)

    F. ALDOMY, M. ALKHAWALDEH1 AND I. B. YOUNIS

    2009-10-01

    Full Text Available Three groups of Shami goats were randomly vaccinated with Brucevac (Rev. 1 vaccine. Group 1 was vaccinated subcutaneously with a full dose (1.54 x 109 organisms. Group 2 was vaccinated conjunctively with one eye drop (5.2 x 108 organisms, while Group 3 was injected subcutaneously with a reduced dose (7.1 x 105 organisms of vaccine. Blood samples were collected before vaccination, two, four, eight, 15 and 24 weeks post vaccination. All samples were tested through CFT, ELISA, SAT and Rose Bengal plate test. All serological tests used detected a higher percentage of vaccinated female kids with a full dose than they did in other groups vaccinated with a reduced dose or with a conjunctival dose of Rev.1 vaccine. The overall results suggested that 100% of animals vaccinated with a conjunctival dose became positive to CFT at two, four, eight and 15 weeks post vaccination, and then the percentage of seropositive animals declined and became 20% at 24 weeks post inoculation. The conjunctival route of vaccination significantly reduced the intensity and duration of the post vaccination serological response, which makes the use of this vaccine compatible with brucellosis programmes, even when these are based on a test-and–slaughter policy. The overall results showed that Shami goats responded to Rev.1 vaccine in the expected way. The majority of animals were seropositive to the CFT by two weeks after vaccination with higher numbers of seropositive animals in the kids group vaccinated with a full dose of Rev.1 vaccine.

  17. Potentiation of a p53-SLP vaccine by cyclophosphamide in ovarian cancer : A single-arm phase II study

    NARCIS (Netherlands)

    Vermeij, Renee; Leffers, Ninke; Hoogeboom, Baukje-Nynke; Hamming, Ineke L. E.; Wolf, Rinze; Reyners, Anna K. L.; Molmans, Barbara H. W.; Hollema, Harry; Bart, Joost; Drijfhout, Jan W.; Oostendorp, Jaap; van der Zee, Ate G. J.; Melief, Cornelis J.; van der Burg, Sjoerd H.; Daemen, Toos; Nijman, Hans W.

    2012-01-01

    The purpose of the current phase II single-arm clinical trial was to evaluate whether pretreatment with low-dose cyclophosphamide improves immunogenicity of a p53-synthetic long peptide (SLP) vaccine in patients with recurrent ovarian cancer. Patients with ovarian cancer with elevated serum levels

  18. Age-dependent decrease of anti-HBs titers and effect of booster doses using 2 different vaccines in Palestinian children vaccinated in early childhood

    Science.gov (United States)

    Qawasmi, Mohammad; Samuh, Monjed; Glebe, Dieter; Gerlich, Wolfram H; Azzeh, Maysa

    2015-01-01

    Immunization against hepatitis B virus (HBV) has proven to be highly effective and led to significant reduction of new infections worldwide. However, protective immunity measured by anti-HBs titers may decrease to critical levels in the years after basal immunization, particularly in case of exposure to HBV variants different from the vaccine strain. We tested 400 Palestinian children between one and 19 years of age for their anti-HBs titer, challenged the immune memory of those with low or absent anti-HBs with 2 types of hepatitis B vaccines and determined thereafter the anti-HBs titer. At the age of one, 92.2% of the children presented with protective anti-HBs titers (≥10 mIU/ml) with the majority having ≥100 mIU/ml. Protective immunity was still high at ages 2 (87.5%) and 4 (95%), declining by age 5 and 6 (from 69.2% to 66.7%) and down to an average of 39.8% between the ages of 7 and 19. 160 children with a nonprotective or low immune response challenged with either the yeast-derived Engerix-B or the mammalian cell-derived preS1-containing Sci-B-Vac vaccine showed an anamnestic immune response. 92.4% and 85.9% of the children challenged with one dose Sci-B-Vac and Engerix-B presented with anti-HBs titers >100 mIU/ml respectively. Our results reveal that vaccine-induced protective anti-HBs titers against HBV decrease rapidly beyond the age of 6 in Palestinian children, but can be strongly enhanced with a single booster vaccine dose, independent of brand and antigen composition. Our data suggest that a booster vaccine dose against HBV during school years may be useful. PMID:25996579

  19. Dose-optimal vaccine allocation over multiple populations

    OpenAIRE

    Duijzer, Evelot; Jaarsveld, Willem; Wallinga, Jacco; Dekker, Rommert

    2015-01-01

    textabstractFor a large number of infectious diseases, vaccination is the most effective way to prevent an epidemic. However, the vaccine stockpile is hardly ever sufficient to treat the entire population, which brings about the challenge of vaccine allocation. To aid decision makers facing this challenge, we provide insights into the structure of this problem. We first investigate the dependence of health benefit on the fraction of people that receive vaccination, where we define health bene...

  20. Dose-optimal vaccine allocation over multiple populations

    NARCIS (Netherlands)

    L.E. Duijzer (Evelot); W.L. van Jaarsveld (Willem); J. Wallinga (Jacco); R. Dekker (Rommert)

    2015-01-01

    textabstractFor a large number of infectious diseases, vaccination is the most effective way to prevent an epidemic. However, the vaccine stockpile is hardly ever sufficient to treat the entire population, which brings about the challenge of vaccine allocation. To aid decision makers facing this

  1. Factors influencing completion of multi-dose vaccine schedules in adolescents: a systematic review

    Directory of Open Access Journals (Sweden)

    K. E. Gallagher

    2016-02-01

    Full Text Available Abstract Background Completion of multiple dose vaccine schedules is crucial to ensure a protective immune response, and maximise vaccine cost-effectiveness. While barriers and facilitators to vaccine uptake have recently been reviewed, there is no comprehensive review of factors influencing subsequent adherence or completion, which is key to achieving vaccine effectiveness. This study identifies and summarises the literature on factors affecting completion of multi-dose vaccine schedules by adolescents. Methods Ten online databases and four websites were searched (February 2014. Studies with analysis of factors predicting completion of multi-dose vaccines were included. Study participants within 9–19 years of age were included in the review. The defined outcome was completion of the vaccine series within 1 year among those who received the first dose. Results Overall, 6159 abstracts were screened, and 502 full texts were reviewed. Sixty one studies were eligible for this review. All except two were set in high-income countries. Included studies evaluated human papillomavirus vaccine, hepatitis A, hepatitis B, and varicella vaccines. Reported vaccine completion rates, among those who initiated vaccination, ranged from 27 % to over 90 %. Minority racial or ethnic groups and inadequate health insurance coverage were risk factors for low completion, irrespective of initiation rates. Parental healthcare seeking behaviour was positively associated with completion. Vaccine delivery in schools was associated with higher completion than delivery in the community or health facilities. Gender, prior healthcare use and socio-economic status rarely remained significant risks or protective factors in multivariate analysis. Conclusions Almost all studies investigating factors affecting completion have been carried out in developed countries and investigate a limited range of variables. Increased understanding of barriers to completion in adolescents will

  2. Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy.

    Science.gov (United States)

    Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A

    2008-09-01

    Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients.

  3. single dose pharmacokinetics of mefloquine in healthy nigerian

    African Journals Online (AJOL)

    BSN

    Mefloquine 500mg single dose was administered and blood samples were collected ... particle size ODS Hypersil (HETP, Macclesfield, UK) at a pressure of 55 Mpa .... dose to area under the plasma drug concentration - time curve, assuming ...

  4. Low-Dose Priming before Vaccination with the Phase I Chloroform-Methanol Residue Vaccine against Q Fever Enhances Humoral and Cellular Immune Responses to Coxiella burnetii▿

    Science.gov (United States)

    Waag, David M.; England, Marilyn J.; Bolt, Christopher R.; Williams, Jim C.

    2008-01-01

    Although the phase I Coxiella burnetii cellular vaccine is completely efficacious in humans, adverse local and systemic reactions may develop if immune individuals are inadvertently vaccinated. The phase I chloroform-methanol residue (CMRI) vaccine was developed as a potentially safer alternative. Human volunteers with no evidence of previous exposure to C. burnetii received a subcutaneous vaccination with the CMRI vaccine in phase I studies under protocol IND 3516 to evaluate the safety and immunogenicity of the vaccine. This clinical trial tested escalating doses of the CMRI vaccine, ranging from 0.3 to 60 μg, followed by a booster dose of 30 μg, in a placebo-controlled study. Although priming doses of the CMRI vaccine did not induce a specific antibody detectable by enzyme-linked immunosorbent assay, booster vaccination stimulated the production of significant levels of anti-C. burnetii antibody. Peripheral blood cells (PBCs) of vaccinees responded to C. burnetii cellular antigen in vitro in a vaccine dose-dependent manner. After the booster dose, PBCs were activated by recall antigen in vitro, regardless of the priming dose. These findings suggest that vaccination with the CMRI vaccine can effectively prime the immune system to mount significant anamnestic responses after infection. PMID:18701647

  5. Low-dose priming before vaccination with the phase I chloroform-methanol residue vaccine against Q fever enhances humoral and cellular immune responses to Coxiella burnetii.

    Science.gov (United States)

    Waag, David M; England, Marilyn J; Bolt, Christopher R; Williams, Jim C

    2008-10-01

    Although the phase I Coxiella burnetii cellular vaccine is completely efficacious in humans, adverse local and systemic reactions may develop if immune individuals are inadvertently vaccinated. The phase I chloroform-methanol residue (CMRI) vaccine was developed as a potentially safer alternative. Human volunteers with no evidence of previous exposure to C. burnetii received a subcutaneous vaccination with the CMRI vaccine in phase I studies under protocol IND 3516 to evaluate the safety and immunogenicity of the vaccine. This clinical trial tested escalating doses of the CMRI vaccine, ranging from 0.3 to 60 microg, followed by a booster dose of 30 microg, in a placebo-controlled study. Although priming doses of the CMRI vaccine did not induce a specific antibody detectable by enzyme-linked immunosorbent assay, booster vaccination stimulated the production of significant levels of anti-C. burnetii antibody. Peripheral blood cells (PBCs) of vaccinees responded to C. burnetii cellular antigen in vitro in a vaccine dose-dependent manner. After the booster dose, PBCs were activated by recall antigen in vitro, regardless of the priming dose. These findings suggest that vaccination with the CMRI vaccine can effectively prime the immune system to mount significant anamnestic responses after infection.

  6. Acoustic neuromas: single dose vs fractionated therapy

    International Nuclear Information System (INIS)

    Fuss, M.; Debus, J.; Lohr, F.; Engenhart-Cabillic, R.; Wannenmacher, M.

    1997-01-01

    Purpose: Radiosurgical treatment (RS) of acoustic neuromas is a well established treatment. However, few data are available concerning conformal fractionated radiotherapy (FT) of this tumor entity. We evaluated treatment outcome and toxicity for both treatment modalities in 41 patients treated at our institution between 1984 and 1997. Material and Methods: All treatments were performed using a specially adapted linear accelerator and circular collimators for convergent beam RS or multi-leaf collimators (leaf thickness 1 or 3mm) for multi-field RS or fractionated treatment. 22 patients (7 male, 15 female, median age 60 years, range 20-83 years) were treated radiosurgically with single doses between 7 and 28 Gray (median 15 Gy) prescribed to the 80% isodose line. Tumor volumes ranged from 0.7 to 10.5 ccm with a median volume of 3.4 ccm. The median number of isocenters was 2 (1-4 isocenters). One patient was treated by a multi-field technique (14 isocentric irregularly shaped noncoplanar fields). 19 patients (5 male, 14 female, median age 55 years, range 20-81 years) were treated with stereotactic conformal radiotherapy. Median dose was 60 Gray with a median daily fraction size of 2 Gy and a median of 3 (1-4) irregularly shaped isocentric fields. Tumor volumes ranged from 0.7 to 32.4 ccm (median 15 ccm). Median follow-up was 30 months (7-149 months) for radiosurgical and 30 months (2-88 months) for fractionated treatment. Seven patients who underwent fractionated treatment had previously undergone neurosurgical resection on the contralateral side. One had undergone radiosurgery on the opposite side before. Results: All tumors were locally controlled. A volume reduction of more than 20% was seen in 16% after RS and 18% following FT. Typical posttherapeutic central reduction of contrast media enhancement was found in 73% following RS after a median of 8 (3-12) months and in 63% following FT after a median of 6 (1-12) months. Temporary brainstem edema was diagnosed in 4

  7. Age at first dose of measles vaccination in Ethiopia | Berhane | East ...

    African Journals Online (AJOL)

    Background: Although measles vaccination is recommended to be given at nine months of age in Ethiopia and in most of sub-Saharan Africa, no information is available about the age at which children actually receive their first dose of measles vaccine. This has important implications in terms of preventing infection and ...

  8. Toward the development of a one-dose classical swine fever subunit vaccine: antigen titration, immunity onset, and duration of immunity

    Science.gov (United States)

    Madera, Rachel F.; Wang, Lihua; Gong, Wenjie; Burakova, Yulia; Buist, Sterling; Nietfeld, Jerome; Henningson, Jamie; Cino-Ozuna, Ada G.; Tu, Changchun

    2018-01-01

    Highly contagious classical swine fever (CSF) remains a major trade and health problem in the pig industry, resulting in large economic losses worldwide. In CSF-endemic countries, attenuated CSF virus (CSFV) vaccines have been routinely used to control the disease. However, eradication of CSFV in a geographical area would require permanent reduction to zero presence of the virus. It is therefore of paramount importance to develop a safe, potent, and non-infectious CSF vaccine. We have previously reported on a cost-effective CSF E2 subunit vaccine, KNB-E2, which can protect against CSF symptoms in a single dose containing 75 µg of recombinant CSFV glycoprotein E2. In this study, we report on a series of animal studies undertaken to elucidate further the efficacy of KNB-E2. We found that pigs vaccinated with a single KNB-E2 dose containing 25 µg of recombinant CSFV glycoprotein E2 were protected from clinical symptoms of CSF. In addition, KNB-E2-mediated reduction of CSF symptoms was observed at two weeks post-vaccination and the vaccinated pigs continued to exhibit reduced CSF clinical signs when virus challenged at two months and four months post-vaccination. These results suggest that KNB-E2 effectively reduces CSF clinical signs, indicating the potential of this vaccine for safely minimizing CSF-related losses. PMID:29510474

  9. Immunogenicity and safety of combined adsorbed low-dose diphtheria, tetanus and inactivated poliovirus vaccine (REVAXIS®) versus combined diphtheria, tetanus and inactivated poliovirus vaccine (DT Polio®) given as a booster dose at 6 years of age

    Science.gov (United States)

    Gajdos, Vincent; Soubeyrand, Benoit; Vidor, Emmanuel; Richard, Patrick; Boyer, Julie; Sadorge, Christine

    2011-01-01

    This randomized, comparative, phase-IIIb study conducted in France aimed to demonstrate whether seroprotection against diphtheria, tetanus and poliomyelitis 1 month after a single dose of REVAXIS (low-dose diphtheria) is non-inferior to seroprotection 1 month after a single dose of DT Polio (standard-dose diphtheria), both vaccines being given as a second booster to healthy children at 6 years of age. Children were randomly assigned to receive a single intramuscular dose of REVAXIS or DT Polio. Primary endpoints were the 1-month post-booster seroprotection rates for diphtheria, tetanus and poliovirus type-1, -2 and -3 antigens. Secondary endpoints were immunogenicity and safety observations. Of 788 children screened, 760 were randomized: REVAXIS group, 384 children; DT Polio group, 376 children. No relevant difference in demographic characteristics at baseline was observed between REVAXIS and DT Polio groups. Noninferiority of REVAXIS compared with DT Polio for seroprotection was demonstrated against diphtheria (respectively 98.6% and 99.3%), tetanus (respectively 99.6% and 100%) and poliovirus antigens (100% for each types in both groups). No allergic reactions to REVAXIS were reported. A benefit/risk ratio in favor of REVAXIS was suggested by the trend towards a better tolerability of REVAXIS compared with DT Polio regarding the rate of severe solicited injection-site reactions. The results support the use of REVAXIS as a booster at 6 years of age in infants who previously received a three-dose primary series within the first 6 months of life and a first booster including diphtheria, tetanus and poliovirus vaccine(s) given before 2 years of age. PMID:21441781

  10. Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.

    Directory of Open Access Journals (Sweden)

    Germain J P Fernando

    Full Text Available BACKGROUND: Over 14 million people die each year from infectious diseases despite extensive vaccine use [1]. The needle and syringe--first invented in 1853--is still the primary delivery device, injecting liquid vaccine into muscle. Vaccines could be far more effective if they were precisely delivered into the narrow layer just beneath the skin surface that contains a much higher density of potent antigen-presenting cells (APCs essential to generate a protective immune response. We hypothesized that successful vaccination could be achieved this way with far lower antigen doses than required by the needle and syringe. METHODOLOGY/PRINCIPAL FINDINGS: To meet this objective, using a probability-based theoretical analysis for targeting skin APCs, we designed the Nanopatch, which contains an array of densely packed projections (21025/cm(2 invisible to the human eye (110 microm in length, tapering to tips with a sharpness of <1000 nm, that are dry-coated with vaccine and applied to the skin for two minutes. Here we show that the Nanopatches deliver a seasonal influenza vaccine (Fluvax 2008 to directly contact thousands of APCs, in excellent agreement with theoretical prediction. By physically targeting vaccine directly to these cells we induced protective levels of functional antibody responses in mice and also protection against an influenza virus challenge that are comparable to the vaccine delivered intramuscularly with the needle and syringe--but with less than 1/100(th of the delivered antigen. CONCLUSIONS/SIGNIFICANCE: Our results represent a marked improvement--an order of magnitude greater than reported by others--for injected doses administered by other delivery methods, without reliance on an added adjuvant, and with only a single vaccination. This study provides a proven mathematical/engineering delivery device template for extension into human studies--and we speculate that successful translation of these findings into humans could

  11. WHO position on the use of fractional doses - June 2017, addendum to vaccines and vaccination against yellow fever WHO: Position paper - June 2013.

    Science.gov (United States)

    World Health Organization

    2017-10-13

    This article presents the World Health Organization's (WHO) recommendations on the use of fractional doses of yellow fever vaccines excerpted from the "Yellow fever vaccine: WHO position on the use of fractional doses - June 2017, Addendum to Vaccines and vaccination against yellow fever WHO: Position Paper - June 2013″, published in the Weekly Epidemiological Record [1,2]. This addendum to the 2013 position paper pertains specifically to use of fractional dose YF (fYF) vaccination (fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as usual per manufacturer recommendations) in the context of YF vaccine supply shortages beyond the capacity of the global stockpile. The current WHO position on the use of yellow fever (YF) vaccine is set out in the 2013 WHO position paper on vaccines and vaccination against YF and those recommendations are unchanged. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of Yellow Fever vaccines were discussed by SAGE in October 2016; evidence presented at these meetings can be accessed at: www.who.int/immunization/sage/meetings/2016/October/presentations_background_docs/en/. Copyright © 2017. Published by Elsevier Ltd.

  12. Duration of protection against hepatitis A for the current two-dose vaccine compared to a three-dose vaccine schedule in children

    Science.gov (United States)

    Raczniak, Gregory A.; Thomas, Timothy K.; Bulkow, Lisa R.; Negus, Susan E.; Zanis, Carolyn L.; Bruce, Michael G.; Spradling, Philip R.; Teshale, Eyasu H.; McMahon, Brian J.

    2015-01-01

    Background Hepatitis A is mostly a self-limiting disease but causes substantial economic burden. Consequently, United States Advisory Committee for Immunization Practices recommends inactivated hepatitis A vaccination for all children beginning at age 1 year and for high risk adults. The hepatitis A vaccine is highly effective but the duration of protection is unknown. Methods We examined the proportion of children with protective hepatitis A antibody levels (anti-HAV ≥20 mIU/mL) as well as the geometric mean concentration (GMC) of anti-HAV in a cross sectional convenience sample of individuals aged 12–24 years, who had been vaccinated with a two-dose schedule in childhood, with the initial dose at least 5 years ago. We compared a subset of data from persons vaccinated with two-doses (720 EL.U.) at age 3–6 years with a demographically similar prospective cohort that received a three-dose (360 EL.U.) schedule and have been followed for 17 years. Results No significant differences were observed when comparing GMC between the two cohorts at 10 (P = 0.467), 12 (P = 0.496), and 14 (P = 0.175) years post-immunization. For the three-dose cohort, protective antibody levels remain for 17 years and have leveled-off over the past 7 years. Conclusion The two- and three-dose schedules provide similar protection >14 years after vaccination, indicating a booster dose is not needed at this time. Plateauing anti-HAV GMC levels suggest protective antibody levels may persist long-term. PMID:23470239

  13. Effectiveness of Brucella abortus Strain 19 single calfhood vaccination in elk (Cervus elaphus)

    Science.gov (United States)

    Roffe, Thomas J.; Jones, Lee C.; Coffin, Kenneth; Sweeney, Steven J.; Williams, Beth; Quist, Charlotte

    2002-01-01

    Brucellosis in Greater Yellowstone Area (GYA) bison and elk has been a source of controversy and focus of the Greater Yellowstone Interagency Brucellosis Committee (GYIBC) for years. Brucellosis has been eradicated from cattle in the 3 states of Wyoming, Montana, and Idaho and all three states currently are classified as “brucellosis free” with regard to livestock. Yet free-ranging elk that attend feedgrounds in the GYA, and bison in Yellowstone and Grand Teton National Parks, still have high seroprevalence to the disease and are viewed as a threat to the state-federal cooperative national brucellosis eradication program. Recently, cattle in eastern Idaho were found infected with brucellosis and transmission was apparently from fed elk. The GYIBC, formed of state and federal agencies involved in wildlife and livestock management in the 3 states, has committed to eventual elimination of the disease from wildlife. Management tools to control or eliminate the disease are limited; however, wildlife vaccination is one of the methods currently employed. Effective wildlife vaccination depends on dose efficacy, deliverability, and safety to non-targeted species. We commenced a single-dose efficacy study of vaccine Brucella abortus strain 19 (S19) in elk in 1999.

  14. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

    Science.gov (United States)

    van Damme, Pierre; Kafeja, Froukje; Anemona, Alessandra; Basile, Venere; Hilbert, Anne Katrin; De Coster, Ilse; Rondini, Simona; Micoli, Francesca; Qasim Khan, Rana M; Marchetti, Elisa; Di Cioccio, Vito; Saul, Allan; Martin, Laura B; Podda, Audino

    2011-01-01

    Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults. Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine. All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. ClinicalTrials.gov NCT01123941 NCT01193907.

  15. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

    Directory of Open Access Journals (Sweden)

    Pierre van Damme

    Full Text Available Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇ for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults.Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen, a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen with the polysaccharide vaccine.All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.ClinicalTrials.gov NCT01123941 NCT01193907.

  16. Dose response and efficacy of a live, attenuated human rotavirus vaccine in Mexican infants.

    Science.gov (United States)

    Ruiz-Palacios, Guillermo M; Guerrero, M Lourdes; Bautista-Márquez, Aurora; Ortega-Gallegos, Hilda; Tuz-Dzib, Fernando; Reyes-González, Leticia; Rosales-Pedraza, Gustavo; Martínez-López, Julia; Castañón-Acosta, Erika; Cervantes, Yolanda; Costa-Clemens, SueAnn; DeVos, Beatrice

    2007-08-01

    Immunization against rotavirus has been proposed as the most cost-effective intervention to reduce the disease burden associated with this infection worldwide. The objective of this study was to determine the dose response, immunogenicity, and efficacy of 2 doses of an oral, attenuated monovalent G1[P8] human rotavirus vaccine in children from the same setting in Mexico, where the natural protection against rotavirus infection was studied. From June 2001 through May 2003, 405 healthy infants were randomly assigned to 1 of 3 vaccine groups (virus concentrations 10(4.7), 10(5.2), and 10(5.8) infectious units) and to a placebo group and were monitored to the age of 2 years. The vaccine/placebo was administered concurrently with diphtheria-tetanus toxoid-pertussis/hepatitis B/Haemophilus influenzae type b vaccine at 2 and 4 months of age. After the administration of the first vaccine/placebo dose, weekly home visits to collect information regarding infant health were conducted. Stool samples were collected during each gastroenteritis episode and tested for rotavirus antigen and serotype. The vaccine was well tolerated and induced a greater rate of seroconversion than observed in infants who received placebo. For the pooled vaccine groups, efficacy after 2 oral doses was 80% and 95% against any and severe rotavirus gastroenteritis, respectively. Efficacy was 100% against severe rotavirus gastroenteritis and 70% against severe gastroenteritis of any cause with the vaccine at the highest virus concentration (10(5.8) infectious units). The predominant infecting rotavirus serotype in this cohort was wild-type G1 (85%). Adverse events, including fever, irritability, loss of appetite, cough, diarrhea, and vomiting, were similar among vaccinees and placebo recipients. This new oral, live, attenuated human rotavirus vaccine was safe, immunogenic, and highly efficacious in preventing any and, more importantly, severe rotavirus gastroenteritis in healthy infants. This vaccine

  17. Mass vaccination with a two-dose oral cholera vaccine in a long-standing refugee camp, Thailand.

    Science.gov (United States)

    Phares, Christina R; Date, Kashmira; Travers, Philippe; Déglise, Carole; Wongjindanon, Nuttapong; Ortega, Luis; Bhuket, Ponchanok Rattanadilok Na

    2016-01-02

    During 2005-2012, surveillance in Maela refugee camp, Thailand, identified four cholera outbreaks, with rates up to 10.7 cases per 1000 refugees. In 2013, the Thailand Ministry of Public Health sponsored a two-dose oral cholera vaccine (OCV) campaign for the approximately 46,000 refugees living in Maela. We enumerated the target population (refugees living in Maela who are ≥1 year old and not pregnant) in a census three months before the campaign and issued barcoded OCV cards to each individual. We conducted the campaign using a fixed-post strategy during two eight-day rounds plus one two-day round for persons who had missed their second dose and recorded vaccine status for each individual. To identify factors associated with no vaccination (versus at least one dose) and those associated with adverse events following immunization (AEFI), we used separate marginal log-binomial regression models with robust variance estimates to account for household clustering. A total of 63,057 OCV doses were administered to a target population of 43,485 refugees. An estimated 35,399 (81%) refugees received at least one dose and 27,658 (64%) received two doses. A total of 993 additional doses (1.5%) were wasted including 297 that were spat out. Only 0.05% of refugees, mostly children, could not be vaccinated due to repeated spitting. Characteristics associated with no vaccination (versus at least one dose) included age ≥15 years (versus 1-14 years), Karen ethnicity (versus any other ethnicity) and, only among adults 15-64 years old, male sex. Passive surveillance identified 84 refugees who experienced 108 AEFI including three serious but coincidental events. The most frequent AEFI were nausea (49%), dizziness (38%), and fever (30%). Overall, AEFI were more prevalent among young children and older adults. Our results suggest that mass vaccination in refugee camps with a two-dose OCV is readily achievable and AEFI are few. Published by Elsevier Ltd.

  18. Immunogenicity to poliovirus type 2 following two doses of fractional intradermal inactivated poliovirus vaccine: A novel dose sparing immunization schedule.

    Science.gov (United States)

    Anand, Abhijeet; Molodecky, Natalie A; Pallansch, Mark A; Sutter, Roland W

    2017-05-19

    The polio eradication endgame strategic plan calls for the sequential removal of Sabin poliovirus serotypes from the trivalent oral poliovirus vaccine (tOPV), starting with type 2, and the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV), to maintain an immunity base against poliovirus type 2. The global removal of oral poliovirus type 2 was successfully implemented in May 2016. However, IPV supply constraints has prevented introduction in 21 countries and led to complete stock-out in >20 countries. We conducted a literature review and contacted corresponding authors of recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose administered intradermally, to conduct additional type 2 immunogenicity analyses of two fIPV doses compared with one full-dose IPV. Four studies were identified that assessed immunogenicity of two fIPV doses compared to one full-dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2 seroconversion rates improving between absolute 19-42% (median: 37%, pvaccine compared to one full-dose IPV. In response to the current IPV shortage, a schedule of two fIPV doses at ages 6 and 14weekshas been endorsed by technical oversight committees and has been introduced in some affected countries. Copyright © 2017. Published by Elsevier Ltd.

  19. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Tapia, Milagritos D; Sow, Samba O; Lyke, Kirsten E; Haidara, Fadima Cheick; Diallo, Fatoumata; Doumbia, Moussa; Traore, Awa; Coulibaly, Flanon; Kodio, Mamoudou; Onwuchekwa, Uma; Sztein, Marcelo B; Wahid, Rezwanul; Campbell, James D; Kieny, Marie-Paule; Moorthy, Vasee; Imoukhuede, Egeruan B; Rampling, Tommy; Roman, Francois; De Ryck, Iris; Bellamy, Abbie R; Dally, Len; Mbaya, Olivier Tshiani; Ploquin, Aurélie; Zhou, Yan; Stanley, Daphne A; Bailer, Robert; Koup, Richard A; Roederer, Mario; Ledgerwood, Julie; Hill, Adrian V S; Ballou, W Ripley; Sullivan, Nancy; Graham, Barney; Levine, Myron M

    2016-01-01

    The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18-50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 10(10) viral particle units (pu), 2·5 × 10(10) pu, 5 × 10(10) pu, or 1 × 10(11) pu; US participants received 1 × 10(10) pu or 1 × 10(11) pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 10(8) plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured

  20. Lack of effect of a booster dose of influenza vaccine in hemodialysis patients.

    Science.gov (United States)

    Tanzi, Elisabetta; Amendola, Antonella; Pariani, Elena; Zappa, Alessandra; Colzani, Daniela; Logias, Franco; Perego, Angelo; Zanetti, Alessandro R

    2007-08-01

    To assess whether the administration of a booster dose of influenza vaccine may enhance immune response in hemodialysis patients, 58 subjects were given two doses of the 2003/2004 season influenza vaccine, 1 month apart. "European Agency for the Evaluation of Medicinal Products" (EMEA) criteria were fully met in terms of percentage of response and of mean-fold increase of hemagglutination inhibiting (HI) antibody titer, but not in terms of seroprotection rates (HI antibody titers > or =1:40). The second vaccine administration did not result in additional increase in seroprotection rate or in geometric mean titers. Protective immune response against the epidemic A/H3N2 Fujian-like strain, antigenically distant from that included in the vaccine (A/Panama/2007/99) was observed in 94.7% of vaccinees protected against the A/H3N2 vaccine strain 1 month after immunization. No adverse reactions were reported during follow-up. The study findings suggest that immune response to influenza vaccination may be suboptimal in hemodialysis patients and that the administration of an additional second dose of vaccine does not improve the humoral response.

  1. Comparison of 2-Dose and 3-Dose 9-Valent Human Papillomavirus Vaccine Schedules in the United States: A Cost-effectiveness Analysis.

    Science.gov (United States)

    Laprise, Jean-François; Markowitz, Lauri E; Chesson, Harrell W; Drolet, Mélanie; Brisson, Marc

    2016-09-01

    A recent clinical trial using the 9-valent human papillomavirus virus (HPV) vaccine has shown that antibody responses after 2 doses are noninferior to those after 3 doses, suggesting that 2 and 3 doses may have comparable vaccine efficacy. We used an individual-based transmission-dynamic model to compare the population-level effectiveness and cost-effectiveness of 2- and 3-dose schedules of 9-valent HPV vaccine in the United States. Our model predicts that if 2 doses of 9-valent vaccine protect for ≥20 years, the additional benefits of a 3-dose schedule are small as compared to those of 2-dose schedules, and 2-dose schedules are likely much more cost-efficient than 3-dose schedules. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. Trial of high-dose Edmonston-Zagreb measles vaccine in Guinea-Bissau

    DEFF Research Database (Denmark)

    Aaby, Peter; Jensen, T G; Hansen, H L

    1988-01-01

    In a randomised study of 558 children in an urban African community, the protective effect of the Edmonston-Zagreb (EZ) measles vaccine given in a dose of 40,000 plaque forming units from the age of 4 months was compared with the effects of a standard dose (6000 tissue culture infectious units...

  3. Tolerance of the human spinal cord to single dose radiosurgery

    International Nuclear Information System (INIS)

    Ryu, S.; Zhu, G.; Yin, F.-F.; Ajlouni, M.; Kim, J.H.

    2003-01-01

    Tolerance of the spinal cord to the single dose of radiation is not well defined. Although there are cases of human spinal cord tolerance from re-irradiation to the same cord level, the information about the tolerance of human spinal cord to single large dose of radiosurgery is not available. We carried out spinal radiosurgery to treat spinal metastasis and studied the single dose tolerance of the human spinal cord in an ongoing dose escalation paradigm. A total of 39 patients with 48 lesions of spinal metastasis were treated with single dose radiosurgery at Henry Ford Hospital. The radiosurgery dose was escalated from 8 Gy to 16 Gy at 2 Gy increment. The radiation dose was prescribed to periphery of the spinal tumor. The radiation dose to the spinal cord was estimated by computerized dosimetry. The median follow-up time was 10 months (range 6-18 months) from the radiosurgery. The endpoint of the study was to demonstrate the efficacy of the spinal radiosurgery and to determine the tolerance of human spinal cord to single dose radiosurgery. The dose to the spinal cord was generally less than 50 % of the prescribed radiation dose. The volume of the spinal cord that received higher than this dose was less than 20 % of the anterior portion of the spinal cord. Maximum single dose of 8 Gy was delivered to the anterior 20 % of the spinal cord in this dose escalation study. The dose volume histogram will be presented. There was no acute or subacute radiation toxicity detected clinically and radiologically during the maximum follow-up of 20 months. Further dose escalation is in progress. The single tolerance dose of the human spinal cord appears to be at least 8 Gy when it was given to the 20 % of the cord volume, although the duration of follow up is not long enough to detect severe late cord toxicity. This study offers a valuable radiobiological basis of the normal spinal cord tolerance, and opens spinal radiosurgery as a safe treatment for spinal metastasis

  4. Persistence of bactericidal antibodies following early infant vaccination with a serogroup B meningococcal vaccine and immunogenicity of a preschool booster dose.

    Science.gov (United States)

    Snape, Matthew D; Saroey, Praveen; John, Tessa M; Robinson, Hannah; Kelly, Sarah; Gossger, Nicoletta; Yu, Ly-Mee; Wang, Huajun; Toneatto, Daniela; Dull, Peter M; Pollard, Andrew J

    2013-10-15

    The multicomponent serogroup B meningococcal (4CMenB) vaccine was recently licensed for use in Europe. There are currently no data on the persistence of bactericidal antibodies induced by use of this vaccine in infants. Our objective was to evaluate serogroup B-specific bactericidal antibodies in children aged 40-44 months previously vaccinated at 2, 4, 6 and 12 months of age. Participants given 4 doses of 4CMenB as infants received a fifth dose of the vaccine at 40-44 months of age. Age-matched participants who were MenB vaccine-naive received 4CMenB and formed the control group. We evaluated human complement serum bactericidal activity (hSBA) titres at baseline and 1 month after each dose of 4CMenB. Before a booster dose at enrolment, 41%-76% of 17 participants previously vaccinated with 4CMenB in infancy had hSBA titres of 4 or greater against 4 reference strains. Before vaccination in the control group (n = 40) these proportions were similar for strains 44/76-SL (63%) and M10713 (68%) but low for strains NZ98/254 (0%) and 5/99 (3%). A booster dose in the 4CMenB-primed participants generated greater increases in hSBA titres than in controls. As has been observed with other meningococcal vaccines, bactericidal antibodies waned after vaccination with 4CMenB administered according to an approved infant vaccination schedule of 2, 4, 6 and 12 months of age, but there was an anamnestic response to a booster dose at 40-44 months of age. If 4CMenB were introduced into routine vaccination schedules, assessment of the need for a booster dose would require data on the impact of these declining titres on vaccine effectiveness. ClinicalTrials.gov, no. NCT01027351.

  5. Coronary vasodilatory action after a single dose of nicorandil

    NARCIS (Netherlands)

    H. Suryapranata (Harry); P.W.J.C. Serruys (Patrick); P.J. de Feyter (Pim); P.D. Verdouw (Pieter); P.G. Hugenholtz (Paul)

    1988-01-01

    textabstractCoronary hemodynamics and vasodilatory effects on major epicardial arteries were investigated after a single dose of nicorandil in 22 patients undergoing cardiac catheterization for suspected coronary artery disease. Nicorandil, 20 mg, was administered sublingually to 11 consecutive

  6. Efficacy of various single-dose regimens of ceftriaxone in ...

    African Journals Online (AJOL)

    The therapeutic efficacy of single intramuscular doses of ceftriaxone (Rocephin; Roche) (62,S, 125 and 250 mg), administered without probenecid, was evaluated in 167 adult males with uncomplicated acute gonococcal urethritis. Cure rates of 100% were achieved at 62,5 mg and 250 mg. In the 125 mg dose group, ...

  7. Immune response and anamnestic immune response in children after a 3-dose primary hepatitis b vaccination

    International Nuclear Information System (INIS)

    Afzal, M.F.; Sultan, M.A.; Saleemi, A.I.

    2017-01-01

    Diseases caused by Hepatitis B virus (HBV) have a worldwide distribution. Pakistan adopted the recommendations of World Health Organization (WHO) for routine universal infant vaccination against hepatitis B in 2002, currently being administered at 6, 10, and 14 weeks of age in a combination vaccine. This study was conducted to determine the immune response and anamnestic immune response in children, 9 months-10 years of age, after a 3-dose primary Hepatitis B vaccination. Methods: This cross sectional study was conducted in the Department of Paediatrics, King Edward Medical University/Mayo Hospital, Lahore, Pakistan, from January to June, 2014. A total of 200 children of either sex between the ages of 9 months to 10 years, docu mented to have received 3 doses of hepatitis B vaccines according to Expanded Program of Immunization (6,10,14 weeks) schedule in infancy, were recruited by consecutive sampling. The level of serum anti-HBsAb by ELIZA was measured. Children with anti-HBs titers =10 mIU/mL were considered to be immune. Those with anti-HBsAb levels <10 mIU/mL were offered a booster dose of infant recombinant hepatitis B vaccine. The second serum sample was obtained 21-28 days following the administration of the booster dose and the anamnestic immune response was measured. Data was analysed using SPSS 17 to determine the relation between time interval since last vaccination and antibody titer. Chi square test was applied. Results: Of the 200 children, protective antibody response was found in 58 percent. Median serological response was 18.60 (range 2.82-65.15). Antibody levels were found to have a statistically significant (p-value 0.019) negative correlation with the time since last administration of vaccine. A booster dose of Hepatitis B vaccine was administered to all non-responders, with each registering a statistically significant (p-value 0.00) anamnestic response. Conclusion: The vaccination schedule with short dosage interval was unable to provide

  8. Persistence of immunity from 1 year of age after one or two doses of hepatitis A vaccine given to children in Argentina

    Directory of Open Access Journals (Sweden)

    Espul C

    2012-08-01

    Full Text Available Carlos Espul,1 Laura Benedetti,2 Héctor Cuello,3 Guy Houillon,4 Anvar Rasuli41Programa de Lucha Contra las Hepatitis Virales, Ministerio de Salud/Hospital Central de Mendoza, 2Programa Provincial de Inmunizaciones, Ministerio de Salud, 3Laboratorio de Virología, Hospital Central de Mendoza, Mendoza, Argentina; 4Sanofi Pasteur, Lyon, FranceBackground: This study was done to determine the immunogenicity of a single dose of hepatitis A vaccine in children, providing needed clinical data on the flexibility of booster administration.Methods: Participants had received one dose of inactivated hepatitis A vaccine (Avaxim™ 80 U Pediatric at 12–23 months of age or two doses of the same vaccine at 12 and 18 months of age prior to enrolment. Anti-hepatitis A antibody concentrations were measured at the first, second, and third year after vaccination. Suspected cases of hepatitis A in participant families were assessed and family socioeconomic data were collected.Results: A series of 546 participants were enrolled. Of 467 (85.5% participants completing 3 years of follow-up, 365 had received a single vaccine dose and 94 had received two vaccine doses. Seropositivity (anti-HAV ≥ 10 mIU/mL at 3 years was 99.7% after one dose and 100% after two doses. At one year, geometric mean concentrations were higher after two doses (1433.9 mIU/mL, 95% confidence interval [CI] 1108–1855 than one (209.7 mIU/mL, 95% CI 190.6–230.6. Geometric mean concentrations decreased in both groups during the study, but remained well above 10 mIU/mL through the third year. The geometric mean of 3-year to one-year anti-hepatitis A concentration ratios was 0.74 (95% CI 0.70–0.79 following one dose and 0.57 (95% CI 0.47–0.70 following two doses. The greatest decrease in geometric mean concentrations occurred during the third year, ie, 21.2% in the one-dose group and 40.8% in the two-dose group. Six participants became seronegative during follow-up and responded strongly to a

  9. Development of a novel, single-cycle replicable rift valley Fever vaccine.

    Directory of Open Access Journals (Sweden)

    Shin Murakami

    2014-03-01

    Full Text Available Rift Valley fever virus (RVFV (genus Phlebovirus, family Bunyaviridae is an arbovirus that causes severe disease in humans and livestock in sub-Saharan African countries. Although the MP-12 strain of RVFV is a live attenuated vaccine candidate, neuroinvasiveness and neurovirulence of MP-12 in mice may be a concern when vaccinating certain individuals, especially those that are immunocompromised. We have developed a novel, single-cycle replicable MP-12 (scMP-12, which carries an L RNA, M RNA mutant encoding a mutant envelope protein lacking an endoplasmic reticulum retrieval signal and defective for membrane fusion function, and S RNA encoding N protein and green fluorescent protein. The scMP-12 underwent efficient amplification, then formed plaques and retained the introduced mutation after serial passages in a cell line stably expressing viral envelope proteins. However, inoculation of the scMP-12 into naïve cells resulted in a single round of viral replication, and production of low levels of noninfectious virus-like particles. Intracranial inoculation of scMP-12 into suckling mice did not cause clinical signs or death, a finding which demonstrated that the scMP-12 lacked neurovirulence. Mice immunized with a single dose of scMP-12 produced neutralizing antibodies, whose titers were higher than in mice immunized with replicon particles carrying L RNA and S RNA encoding N protein and green fluorescent protein. Moreover, 90% of the scMP-12-immunized mice were protected from wild-type RVFV challenge by efficiently suppressing viremia and replication of the challenge virus in the liver and the spleen. These data demonstrated that scMP-12 is a safe and immunogenic RVFV vaccine candidate.

  10. Impact and Cost-effectiveness of 3 Doses of 9-Valent Human Papillomavirus (HPV) Vaccine Among US Females Previously Vaccinated With 4-Valent HPV Vaccine.

    Science.gov (United States)

    Chesson, Harrell W; Laprise, Jean-François; Brisson, Marc; Markowitz, Lauri E

    2016-06-01

    We estimated the potential impact and cost-effectiveness of providing 3-doses of nonavalent human papillomavirus (HPV) vaccine (9vHPV) to females aged 13-18 years who had previously completed a series of quadrivalent HPV vaccine (4vHPV), a strategy we refer to as "additional 9vHPV vaccination." We used 2 distinct models: (1) the simplified model, which is among the most basic of the published dynamic HPV models, and (2) the US HPV-ADVISE model, a complex, stochastic, individual-based transmission-dynamic model. When assuming no 4vHPV cross-protection, the incremental cost per quality-adjusted life-year (QALY) gained by additional 9vHPV vaccination was $146 200 in the simplified model and $108 200 in the US HPV-ADVISE model ($191 800 when assuming 4vHPV cross-protection). In 1-way sensitivity analyses in the scenario of no 4vHPV cross-protection, the simplified model results ranged from $70 300 to $182 000, and the US HPV-ADVISE model results ranged from $97 600 to $118 900. The average cost per QALY gained by additional 9vHPV vaccination exceeded $100 000 in both models. However, the results varied considerably in sensitivity and uncertainty analyses. Additional 9vHPV vaccination is likely not as efficient as many other potential HPV vaccination strategies, such as increasing primary 9vHPV vaccine coverage. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  11. Intradermal Administration of Fractional Doses of Inactivated Poliovirus Vaccine: A Dose-Sparing Option for Polio Immunization.

    Science.gov (United States)

    Okayasu, Hiromasa; Sein, Carolyn; Chang Blanc, Diana; Gonzalez, Alejandro Ramirez; Zehrung, Darin; Jarrahian, Courtney; Macklin, Grace; Sutter, Roland W

    2017-07-01

    A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  12. Assessment of the hepatitis B birth dose vaccination program, Papua New Guinea, 2014.

    Science.gov (United States)

    Wiesen, Eric; Lagani, William; Sui, Gerard; Arava, Johnnie; Reza, Salim; Diorditsa, Sergey; Lin, Yung-Ching

    2016-01-12

    Papua New Guinea (PNG) implemented hepatitis B birth dose (BD) vaccination in 2005 yet since that time coverage has remained low, allowing mother-to-child transmission to occur. We conducted a field assessment of the BD vaccination program to develop strategies for improving the BD coverage. We selected five provinces with higher hepatitis B prevalence and five with lower prevalence based on the results of a 2013 hepatitis B serological survey. Within each province, we interviewed district and provincial health officers, health workers, village volunteers, and caregivers from ten randomly selected health facilities. Data were collected on knowledge, practice, vaccine management and data recording/reporting. To identify enabling factors and barriers, we compared health facilities with higher BD coverage with those with lower coverage, and compared caregivers whose children received BD with those whose children did not. Overall timely BD coverage was 31% and BD vaccination was taking place in 81% of sampled health facilities. Lack of cold chain and vaccine were the major reasons for not providing the BD. Insufficiencies in supervision, vaccine management, community outreach, and data management were identified as obstacles to achieving high timely hepatitis B BD coverage. Good supervision, knowledge of hepatitis B and hepatitis B vaccination, antenatal care including information about the hepatitis B BD, provision of vaccine refrigerators in maternity wards, and outreach vaccination for home deliveries were associated with higher timely BD coverage. Several steps will likely be effective in improving BD coverage: strengthening training and supervision among health workers and officers, educating caregivers on the benefits of the BD and delivery in health facilities, improving vaccine management, and improving data quality. Considerable effort and leadership will be needed to achieve these steps. Copyright © 2015. Published by Elsevier Ltd.

  13. Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults.

    Science.gov (United States)

    Pathan, Ansar A; Minassian, Angela M; Sander, Clare R; Rowland, Rosalind; Porter, David W; Poulton, Ian D; Hill, Adrian V S; Fletcher, Helen A; McShane, Helen

    2012-08-17

    A non-randomised, open-label, Phase I safety and immunogenicity dose-finding study to assess the safety and immunogenicity of the candidate TB vaccine Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) from Mycobacterium tuberculosis (MTB) in healthy adult volunteers previously vaccinated with BCG. Healthy BCG-vaccinated volunteers were vaccinated with either 1×10(7) or 1×10(8)PFU of MVA85A. All adverse events were documented and antigen specific T cell responses were measured using an ex vivo IFN-γ ELISPOT assay. Safety and immunogenicity were compared between the 2 dose groups and with a previous trial in which a dose of 5×10(7)PFU MVA85A had been administered. There were no serious adverse events recorded following administration of either 1×10(7) or 1×10(8)PFU of MVA85A. Systemic adverse events were more frequently reported following administration of 1×10(8)PFU of MVA85A when compared to either 5×10(7) or 1×10(7)PFU of MVA85A but were mild or moderate in severity and resolved completely within 7 days of immunisation. Antigen specific T cell responses as measured by the IFN-γ ELISPOT were significantly higher following immunisation in adults receiving 1×10(8)PFU compared to the 5×10(7) and 1×10(7) doses. Additionally, a broader range of Ag85A epitopes are detected following 1×10(8)PFU of MVA85A. A higher dose of 1×10(8)PFU of MVA85A is well-tolerated, increases the frequency of IFN-γ secreting T cells detected following immunisation and broadens the range of Ag85A epitopes detected. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Mexico introduces pentavalent vaccine.

    Science.gov (United States)

    1999-08-01

    Combination vaccines have been introduced in Mexico. The national immunization program has incorporated the measles-mumps-rubella (MMR) vaccines in 1998, and the pentavalent vaccine in 1999. The two categories of antigen composition in combination vaccines are: 1) multiple different antigenic types of a single pathogen, such as the 23 valent pneumococcal polysaccharide vaccine, and 2) antigens from different pathogens causing different diseases, such as the DPT and MMR vaccines. Pentavalent vaccines are included in the second category. The vaccine protects against diphtheria, tetanus, pertussis, hepatitis B, and other diseases produced by Haemophilus influenzae type b (Hib). Combined diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenza type b (DTP-HB/Hib) vaccine has been distributed to 87% of Mexican children under 1 year of age. Over 800,000 doses of pentavalent vaccine have been administered.

  15. Evaluation of the sterility of single-dose medications used in a multiple-dose fashion.

    Science.gov (United States)

    Martin, Elizabeth P; Mukherjee, Jean; Sharp, Claire R; Sinnott-Stutzman, Virginia B

    2017-11-01

    Bacterial proliferation was evaluated in single-dose medications used in a multi-dose fashion and when medications were intentionally inoculated with bacteria. Of 5 experimentally punctured medications, 1 of 75 vials (50% dextrose) became contaminated. When intentionally inoculated, hydroxyethyl starch and heparinized saline supported microbial growth. Based on these findings, it is recommended that hydroxyethyl starch and heparinized saline not be used in a multi-dose fashion.

  16. Efficacy of one dose vaccination against experimental infection with two Mycoplasma hyopneumoniae strains.

    Science.gov (United States)

    Michiels, Annelies; Arsenakis, Ioannis; Boyen, Filip; Krejci, Roman; Haesebrouck, Freddy; Maes, Dominiek

    2017-08-29

    Mycoplasma hyopneumoniae (M. hyopneumoniae) is the primary agent of enzootic pneumonia in pigs. Pigs are often infected with different M. hyopneumoniae strains. This study assessed the efficacy of vaccination against experimental infection with two genetically different M. hyopneumoniae strains in weaned piglets. At 33 days of age (D0), 45 M. hyopneumoniae-free piglets were randomly assigned to three different groups: 1) negative control group (NCG; n = 5): not vaccinated, not infected, 2) positive control group (PCG; n = 20): not vaccinated, infected, and 3) vaccination group (VG; n = 20): single vaccination with an inactivated whole-cell M. hyopneumoniae vaccine (Hyogen®, Ceva) (D1), infected. The PCG and VG were endotracheally inoculated with 7 × 10 7 CCU in 7 ml of the highly virulent M. hyopneumoniae strain F7.2C (D24) and 7 × 10 7 CCU in 7 ml low virulent strain F1.12A (D25). A respiratory disease score (RDS) was assessed from D24 until D53. At D53 (euthanasia), macroscopic lung lesions (MLL) were scored, log copies of M. hyopneumoniae DNA (qPCR) and IL-1 and IL-6-concentrations (ELISA) on bronchoalveolar lavage fluid were determined. The RDS and MLL at euthanasia were respectively 0, 1.20 and 0.55 (P hyopneumoniae strain as the vaccinated pigs coughed significantly less, and showed significantly less lung lesions compared to the non-vaccinated challenged pigs: the vaccinated animals showed a 52.9% lower RDS and 91.0% lower MLL compared to the PCG. In the bronchoalveolar lavage fluid collected at the necropsy of the vaccinated pigs, a significantly lower amount of M. hyopneumoniae-DNA and a significantly lower IL-1 and IL-6 concentration was found compared to the pigs of the PCG.

  17. Does Nigeria need the birth dose of the hepatitis B vaccine? | Sadoh ...

    African Journals Online (AJOL)

    The control of hepatitis B infection involves several strategies of which the most effective is vaccination. Schedules which include a birth dose (which can prevent vertical transmission when administered within 24 hours of birth) are recommended for use in countries with a high rate of vertical transmission. Nigeria is highly ...

  18. Does Nigeria need the birth dose of the hepatitis B vaccine?

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-11-26

    Nov 26, 2013 ... of health care workers on ensuring the timely receipt of the birth dose of HBV vaccine and health educa- tion of mothers and the community ... Sub Saharan Africa, the Pacific Islands and the Amazon basin. .... infection even though over 80% had received antenatal .... Ugbebor O, Aigbirior M, Osazuwa.

  19. Immune response after one or two doses of pandemic influenza A (H1N1) monovalent, AS03-adjuvanted vaccine in HIV infected adults

    DEFF Research Database (Denmark)

    Bybeck Nielsen, Allan; Nielsen, Henriette Schjønning; Nielsen, Lars

    2012-01-01

    INTRODUCTION: Continued research is needed to evaluate and improve the immunogenicity of influenza vaccines in HIV infected patients. We aimed to determine the antibody responses after one or two doses of the AS03-adjuvanted pandemic influenza A (H1N1) vaccine in HIV infected patients. METHOD......: Following the influenza season 2009/2010, 219 HIV infected patients were included and divided into three groups depending on whether they received none (n=60), one (n=31) or two (n=128) doses of pandemic influenza A (H1N1) vaccine. At inclusion, antibody titers for all patients were analyzed and compared...... to pre-pandemic antibody titers analyzed from serum samples in a local storage facility. RESULTS: 4-9 months after a single immunization, we found a seroprotection rate of 77.4% and seroconversion rate of 67.7%. After two immunizations the rates increased significantly to seroprotection rate of 97...

  20. Systematic literature review comparing rapid 3-dose administration of the GSK tick-borne encephalitis vaccine with other primary immunization schedules.

    Science.gov (United States)

    Galgani, Ilaria; Bunge, Eveline M; Hendriks, Lisa; Schludermann, Christopher; Marano, Cinzia; De Moerlooze, Laurence

    2017-09-01

    Tick-borne encephalitis (TBE), which is endemic across large regions of Europe and Asia, is most effectively prevented through vaccination. Three-dose primary TBE vaccination schedules are either rapid (0,7,21-days) or conventional (0,28-84-days, 9-12-months). The second dose can also be administered at 14 days for faster priming and sero-protection). Areas covered: We used a three-step selection process to identify 21 publications comparing the immunogenicity and/or safety of different schedules. Expert commentary: Priming with two or three TBE vaccine doses was highly immunogenic. After conventional priming (0-28 days), 95% adults and ≥95% children had neutralization test (NT) titers ≥10 at 14 days post-dose-2 compared with 92% adults and 99% children at 21 days post-dose-3 (rapid schedule). Most subjects retained NT titers ≥10 at day 300. A single booster dose induced a strong immune response in all subjects irrespective of primary vaccination schedule or elapsed time since priming. GMT peaked at 42 days post-dose-1 (i.e., 21 days post-dose 3 [rapid-schedule], or 14-28 days post-dose-2 [conventional-schedule]), and declined thereafter. Adverse events were generally rare and declined with increasing doses. In the absence of data to recommend one particular schedule, the regimen choice will remain at the physician's discretion, based on patient constraints and availability.

  1. Two-dose strategies for human papillomavirus vaccination: how well do they need to protect?

    Science.gov (United States)

    Jit, Mark; Choi, Yoon Hong; Laprise, Jean-François; Boily, Marie-Claude; Drolet, Mélanie; Brisson, Marc

    2014-05-30

    Two-dose human papillomavirus (HPV) vaccine schedules may provide short-term protection but their long-term population impact is unknown. Two models of HPV transmission and associated cervical disease (squamous and glandular, neoplasia and cancer) were fitted to data from England and Canada on HPV epidemiology, sexual behaviour, cervical screening outcomes and cervical cancer incidence. Models suggest that at 40-80% coverage, if two-dose schedules protect vaccinees for 20 years, then the benefits of the third dose are small. If two doses protect for 10 years, then the third dose may prevent as many cancers as the first two. At 80% coverage, numbers needed to receive a third dose to prevent an additional cancer are 5900-110,000 (England), 3000-5100 (Canada) with 20 years two-dose protection, and 2000-5300 (England), 760-950 (Canada) with 10 years two-dose protection. Results enable decision makers to quantify risks associated with two-dose schedules despite remaining uncertainties in vaccine duration and cross-protection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Single point estimation of phenytoin dosing: a reappraisal.

    Science.gov (United States)

    Koup, J R; Gibaldi, M; Godolphin, W

    1981-11-01

    A previously proposed method for estimation of phenytoin dosing requirement using a single serum sample obtained 24 hours after intravenous loading dose (18 mg/Kg) has been re-evaluated. Using more realistic values for the volume of distribution of phenytoin (0.4 to 1.2 L/Kg), simulations indicate that the proposed method will fail to consistently predict dosage requirements. Additional simulations indicate that two samples obtained during the 24 hour interval following the iv loading dose could be used to more reliably predict phenytoin dose requirement. Because of the nonlinear relationship which exists between phenytoin dose administration rate (RO) and the mean steady state serum concentration (CSS), small errors in prediction of the required RO result in much larger errors in CSS.

  3. The dose dependency of the over-dispersion of quartz OSL single grain dose distributions

    DEFF Research Database (Denmark)

    Thomsen, Kristina Jørkov; Murray, Andrew S.; Jain, Mayank

    2012-01-01

    The use of single grain quartz OSL dating has become widespread over the past decade, particularly with application to samples likely to have been incompletely bleached before burial. By reducing the aliquot size to a single grain the probability of identifying the grain population most likely...... to have been well-bleached at deposition is maximised and thus the accuracy with which the equivalent dose can be determined is – at least in principle – improved. However, analysis of single grain dose distributions requires knowledge of the dispersion of the well-bleached part of the dose distribution....... This can be estimated by measurement of a suitable analogue, e.g. a well-bleached aeolian sample, but this requires such an analogue to be available, and in addition the assumptions that the sample is in fact a) well-bleached, and b) has a similar dose rate heterogeneity to the fossil deposit. Finally...

  4. Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults

    Directory of Open Access Journals (Sweden)

    L. Coughlan

    2018-03-01

    Full Text Available Background: T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP and matrix protein-1 (M1. We now report on the safety and long-term immunogenicity of multiple combination regimes of these vaccines in young and older adults. Methods: We conducted a Phase I open-label, randomized, multi-center study in 49 subjects aged 18–46 years and 24 subjects aged 50 years or over. Following vaccination, adverse events were recorded and the kinetics of the T cell response determined at multiple time points for up to 18 months. Findings: Both vaccines were well tolerated. A two dose heterologous vaccination regimen significantly increased the magnitude of pre-existing T-cell responses to NP and M1 after both doses in young and older adults. The fold-increase and peak immune responses after a single MVA-NP + M1 vaccination was significantly higher compared to ChAdOx1 NP + M1. In a mixed regression model, T-cell responses over 18 months were significantly higher following the two dose vaccination regimen of MVA/ChAdOx1 NP + M1. Interpretation: A two dose heterologous vaccination regimen of MVA/ChAdOx1 NP + M1 was safe and immunogenic in young and older adults, offering a promising vaccination strategy for inducing long-term broadly cross-reactive protection against influenza A. Funding Source: Medical Research Council UK, NIHR BMRC Oxford. Keywords: Influenza, T-cell responses, Influenza vaccines, Viral vectors, Adults, Older adults

  5. Measurement of the equivalent dose in quartz using a regenerative-dose single-aliquot protocol

    International Nuclear Information System (INIS)

    Murray, A.S.; Roberts, R.G.

    1998-01-01

    The principles behind a regenerative-dose single-aliquot protocol are outlined. It is shown for three laboratory-bleached Australian sedimentary quartz samples that the relative change in sensitivity of the optically stimulated luminescence (OSL) during a repeated measurement cycle (consisting of a dose followed by a 10 s preheat at a given temperature and then a 100 s exposure to blue/green light at 125 deg. C) is very similar to that of the 110 deg. C thermoluminescence (TL) peak measured during the preheat cycle. The absolute change in the TL sensitivity with preheat temperature is different for samples containing a natural or a regenerative dose. Furthermore, the absolute change in sensitivity in both the OSL and TL signals is non-linear with regeneration cycle, but the relative change in the OSL signal compared to the following 110 deg. C TL measurement is well approximated by a straight line. Both signals are thought to use the same luminescence centres, and so some common behaviour is not unexpected. A new regenerative-dose protocol is presented which makes use of this linear relationship to correct for sensitivity changes with regeneration cycle, and requires only one aliquot for the estimation of the equivalent dose (D e ). The protocol has been applied to quartz from nine Australian sites. To illustrate the value of the regenerative-dose single-aliquot approach, the apparent values of D e for 13 samples, containing doses of between 0.01 and 100 Gy, have been measured at various preheat temperatures of between 160 and 300 deg. C, using a single aliquot for each D e measurement. Excellent agreement is found between these single-aliquot estimates of D e and those obtained from additive-dose multiple-aliquot and single-aliquot protocols, over the entire dose range

  6. A Single 17D Yellow Fever Vaccination Provides Lifelong Immunity; Characterization of Yellow-Fever-Specific Neutralizing Antibody and T-Cell Responses after Vaccination

    NARCIS (Netherlands)

    Wieten, Rosanne W.; Jonker, Emile F. F.; van Leeuwen, Ester M. M.; Remmerswaal, Ester B. M.; ten Berge, Ineke J. M.; de Visser, Adriëtte W.; van Genderen, Perry J. J.; Goorhuis, Abraham; Visser, Leo G.; Grobusch, Martin P.; de Bree, Godelieve J.

    2016-01-01

    Prompted by recent amendments of Yellow Fever (YF) vaccination guidelines from boost to single vaccination strategy and the paucity of clinical data to support this adjustment, we used the profile of the YF-specific CD8+ T-cell subset profiles after primary vaccination and neutralizing antibodies as

  7. Low frequency of side effects following an incidental 25 times concentrated dose of yellow fever vaccine

    Directory of Open Access Journals (Sweden)

    Rabello Ana

    2002-01-01

    Full Text Available In August/1999, a group of 14 adults from the staff of a private hospital in Contagem -- Minas Gerais State, Brazil, received unintentionally a 25 times concentrated dose of the 17-DD yellow fever vaccine (Bio-Manguinhos, due to a mistake at the reconstitution step. All patients were clinically and laboratorially evaluated at days 5, 13 and 35 post vaccination. Frequency of side effects and clinical observations of this group of individuals were not different from the observed in recipients immunized with normal doses of the vaccine. At the second and third evaluation none of the subjects reported symptoms. None of the patients presented abnormalities at the physical examination at none of the time points and in all cases the blood examination was normal, except for a reduced number of platelets that was detected in one subject at the first and second evaluation and reverted to normal at third evaluation. At the first evaluation point, 8 subjects were serum negative and 6 serum positive for yellow fever at the plaque reduction neutralization test. In 5 subjects the observed titre was 10 times higher as the baseline of 2.36 Log10 mUI/ml. The samples collected at second and third evaluation (13th and 35th days demonstrated that all subjects responded to the vaccination with the exception of one that did not present a positive result in any of the samples collected. This evaluation confirms the safety of the 17-DD yellow fever vaccine.

  8. Serological response of pigs to a standard and increased dose of foot-and-mouth disease vaccine

    International Nuclear Information System (INIS)

    Sims, L.D.; Dyrting, K.C.; Wong, K.W.

    2000-01-01

    Two randomly allocated age-matched groups of 17 conventionally reared pigs derived from vaccinated sows were vaccinated at 10 and 14 weeks of age with a commercially available foot-and-mouth disease vaccine, using either a 1 mL dose or a 3 mL dose. A control group of four pigs was left unvaccinated. Pigs were monitored at regular intervals from birth to 26 weeks of age for antibodies to FMD Type O virus using a liquid phase blocking ELISA. At 12 weeks post vaccination, significantly more pigs vaccinated twice with 3 mL of vaccine had developed antibodies against Type O foot-and-mouth disease virus (at an ELISA titre of 90 or greater) than those vaccinated twice with 1 mL of vaccine (chi-squared test, p = 0.006). Overall, the response to vaccination was poor in both groups of pigs. Four weeks after the first dose of vaccine only four pigs had detectable antibody against the virus. Twelve weeks after the second dose of vaccine only 60% of pigs given the 3 mL dose and 15% of pigs given the 1 mL dose had ELISA titres of 90 or greater. Maternal antibody is considered to have played a role in this poor response, as it was present in 27 of the 34 vaccinated pigs at the time of first vaccination. Two pigs in the unvaccinated control group developed a low level antibody response (antibody titre <90). Infection with field virus was considered a highly unlikely cause of this. These results show, that under field conditions using a widely adopted protocol not all pigs vaccinated develop antibody to foot-and-mouth disease. This, in part, may explain why vaccination programmes against this disease in Hong Kong seem to have a limited impact. The results also suggest, that an increased dose of vaccine has a positive effect on the humoral immune response against FMD virus and may improve protection against this disease. Timing of vaccination needs to be re-evaluated to reduce the impact of maternally derived antibodies. (author)

  9. Doses per vaccine vial container: An understated and underestimated driver of performance that needs more evidence.

    Science.gov (United States)

    Heaton, Alexis; Krudwig, Kirstin; Lorenson, Tina; Burgess, Craig; Cunningham, Andrew; Steinglass, Robert

    2017-04-19

    The widespread use of multidose vaccine containers in low and middle income countries' immunization programs is assumed to have multiple benefits and efficiencies for health systems, yet the broader impacts on immunization coverage, costs, and safety are not well understood. To document what is known on this topic, how it has been studied, and confirm the gaps in evidence that allow us to assess the complex system interactions, the authors undertook a review of published literature that explored the relationship between doses per container and immunization systems. The relationships examined in this study are organized within a systems framework consisting of operational costs, timely coverage, safety, product costs/wastage, and policy/correct use, with the idea that a change in dose per container affects all of them, and the optimal solution will depend on what is prioritized and used to measure performance. Studies on this topic are limited and largely rely on modeling to assess the relationship between doses per container and other aspects of immunization systems. Very few studies attempt to look at how a change in doses per container affects vaccination coverage rates and other systems components simultaneously. This article summarizes the published knowledge on this topic to date and suggests areas of current and future research to ultimately improve decision making around vaccine doses per container and increase understanding of how this decision relates to other program goals. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  10. Efficacy of single calfhood vaccination of elk with Brucella abortus strain 19

    Science.gov (United States)

    Roffe, T.J.; Jones, L.C.; Coffin, K.; Drew, M.L.; Sweeney, Steven J.; Hagius, S.D.; Elzer, P.H.; Davis, D.

    2004-01-01

    Brucellosis has been eradicated from cattle in the states of Wyoming, Montana, and Idaho, USA. However, free-ranging elk (Cervus elaphus) that use feedgrounds in the Greater Yellowstone Area (GYA) and bison (Bison bison) in Yellowstone and Grand Teton national parks still have high seroprevalence to the disease and have caused loss of brucellosis-free status in Wyoming. Management tools to control or eliminate the disease are limited; however, wildlife vaccination is among the methods currently used by wildlife managers in Wyoming. We conducted a controlled challenge study of single calfhood vaccination. Elk calves, caught in January and February of 1999 and 2000 and acclimated to captivity for 3 weeks, were randomly assigned to control or vaccinate groups. The vaccinate groups received Brucetta abortus vaccine strain 19 (S19) by hand-delivered intramuscular injection. Calves were raised to adulthood and bred at either 2.5 or 3.5 years of age for 2000 and 1999 captures, respectively. Eighty-nine (44 controls, 45 vaccinates) pregnant elk entered the challenge portion of the study. We challenged elk at mid-gestation with pathogenic B. abortus strain 2308 by intraconjunctival instillation. Abortion occurred in significantly more (P = 0.002) controls (42; 93%) than vaccinates (32; 71%), and vaccine protected 25% of the vaccinate group. We used Brucella culture of fetus/calf tissues to determine the efficacy of vaccination for preventing infection, and we found that the number of infected fetuses/calves did not differ between controls and vaccinates (P = 0.14). Based on these data, single calfhood vaccination with S19 has low efficacy, will likely have only little to moderate effect on Brucella prevalence in elk, and is unlikely to eradicate the disease in wildlife of the GYA.

  11. Efficacy of various single-dose regimens of ceftriaxone in ...

    African Journals Online (AJOL)

    1990-08-18

    Aug 18, 1990 ... The therapeutic efficacy of single intramuscular doses of ceftriaxone (Rocephin; Roche) (62,S, 125 and 250 mg), admini- stered without probenecid, was evaluated in 167 adult males with uncomplicated acute gonococcal urethritis. Cure rates of 100% were achieved at 62,5 mg and 250 mg. In the 125 mg.

  12. Immunogenicity of aluminum-adsorbed hepatitis A vaccine (Havrix®) administered as a third dose after primary doses of Japanese aluminum-free hepatitis A vaccine (Aimmugen®) for Japanese travelers to endemic countries.

    Science.gov (United States)

    Fukushima, Shinji; Kiyohara, Tomoko; Ishii, Koji; Nakano, Takashi; Hamada, Atsuo

    2017-11-07

    Hepatitis A vaccination is recommended for travelers to endemic countries. Several inactivated aluminum-adsorbed hepatitis A vaccines are available worldwide, but only one licensed hepatitis A vaccine is available in Japan. This vaccine is a lyophilized inactivated aluminum-free hepatitis A vaccine (Aimmugen®). The standard schedule of Aimmugen® is three doses (at 0, 2-4 weeks, and 6 months). Japanese people will go abroad after receiving 2 doses of Aimmugen®. Some long-term travelers will receive the third dose of hepatitis A vaccine at their destination, at 6-24 months after 2 doses of Aimmugen®. Aimmugen® is not available in countries other than Japan. They receive inactivated aluminum-adsorbed hepatitis A vaccine instead of a third dose of Aimmugen®. This study was undertaken to determine whether the booster vaccination with an aluminum-adsorbed hepatitis A vaccine is effective following two doses of Aimmugen®. Subjects were healthy Japanese adults aged 20 years or older who had received two doses of Aimmugen®. Subjects received a booster dose of Havrix®1440 intramuscularly as the third dose. Serology samples for hepatitis A virus antibody titers were taken 4-6 weeks later. Anti-hepatitis A virus antibody titers were measured by an inhibition enzyme-linked immunosorbent assay. Subjects were 20 healthy Japanese adults, 6 men and 14 women. The mean age ± standard deviation was 37.2 ± 13.3. The seroprotection rate (SPR, anti-hepatitis A virus antibody titer ≥10 mIU/mL) was 85% at enrollment, and increased to 100% after vaccination with Havrix®. The geometric mean anti-hepatitis A virus antibody titer increased from 39.8 mIU/mL to 2938.2 mIU/mL. The three scheduled doses consisting of two doses of Aimmugen® plus a third dose with Havrix® is more immunogenic than using only two doses of Aimmugen®. The vaccination with Havrix® could be allowed to be used instead of a third dose of Aimmugen®. (UMIN000009351). Copyright © 2017 Elsevier Ltd. All

  13. Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges.

    Directory of Open Access Journals (Sweden)

    Roland R Regoes

    2005-08-01

    Full Text Available Trials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against "real life" exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses.Using statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success.Preclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.

  14. Assessment of mumps-containing vaccine effectiveness during an outbreak: Importance to introduce the 2-dose schedule for China.

    Science.gov (United States)

    Ma, Chao; Liu, Yan; Tang, Jihai; Jia, Haimei; Qin, Wei; Su, Ying; Wang, Huaqing; Hao, Lixin

    2018-01-29

    China has used 3 different mumps-containing vaccines (MuCV) since 1990: monovalent mumps vaccine, measles-mumps (MM) vaccine, and measles-mumps-rubella (MMR) vaccine, and one dose MuCV (using MMR at 18 months) has been included in the EPI since 2007. MuCV effectiveness has been of concern following large-scale mumps outbreaks. In 2015, an outbreak of mumps occurred in a primary school, which allow us assess vaccine effectiveness of different MuCVs. All children in the school were studied as a retrospective cohort. Vaccination histories and case information were obtained from vaccination records and clinic/hospital logs. Parental questionnaires were used to confirm students' illnesses and calculate attack rate (AR). VE was assessed using the formula, VE = (AR in unvaccinated students- AR in the vaccinated students) / (AR in unvaccinated students). VEs of different type of MuCV were compared. In total, 283 students were identified as clinical mumps among the 2370 students, and 1908 students were included for MuCV VE assessment. 213 (including 21 [8.9%] patients) were 2-dose MuCV recipients (AR: 9.9%), 1165 (including 123 [51.9%] patients) were 1-dose recipients (AR: 10.6%), and 530 (including 93 [39.2%] patients) were unvaccinated (AR: 17.5%). VE was 44% for 2 doses and 40% for one dose. For one-MuCV-dose students, estimated mumps VE was 63% for vaccinated within 3 years (between vaccination and this outbreak); 50% for vaccinated within 3 to 5 years; and 34% for vaccinated more than 5 years. Comparing VE by vaccine type and 5-year interval since vaccination, VE for MMR was 60%, which was consistently higher than VE for monovalent mumps vaccine (22%) and MM (2%). This outbreak was associated with low and declining 1-dose MuCV effectiveness. China's immunization program should evaluate the potential of a 2-dose MMR schedule to adequately control mumps.

  15. The dose dependency of the over-dispersion of quartz OSL single grain dose distributions

    International Nuclear Information System (INIS)

    Thomsen, Kristina J.; Murray, Andrew; Jain, Mayank

    2012-01-01

    The use of single grain quartz OSL dating has become widespread over the past decade, particularly with application to samples likely to have been incompletely bleached before burial. By reducing the aliquot size to a single grain the probability of identifying the grain population most likely to have been well-bleached at deposition is maximised and thus the accuracy with which the equivalent dose can be determined is – at least in principle – improved. However, analysis of single grain dose distributions requires knowledge of the dispersion of the well-bleached part of the dose distribution. This can be estimated by measurement of a suitable analogue, e.g. a well-bleached aeolian sample, but this requires such an analogue to be available, and in addition the assumptions that the sample is in fact a) well-bleached, and b) has a similar dose rate heterogeneity to the fossil deposit. Finally, it is an implicit assumption in such analysis that any over-dispersion is not significantly dose dependent. In this study we have undertaken laboratory investigations of the dose dependency of over-dispersion using a well-bleached modern sample with an average measured dose of 36 ± 3 mGy. This sample was prepared as heated (750 °C for 1 h), bleached and untreated portions which were then given uniform gamma doses ranging from 100 mGy to 208 Gy. We show that for these samples the relative laboratory over-dispersion is not constant as a function of dose and that the over-dispersion is smaller in heated samples. We also show that the dim grains in the distributions have a greater over-dispersion than the bright grains, implying that insensitive samples will have greater values of over-dispersion than sensitive samples.

  16. Safety and Immunogenicity of Full-Dose Trivalent Inactivated Influenza Vaccine (TIV) Compared With Half-Dose TIV Administered to Children 6 Through 35 Months of Age.

    Science.gov (United States)

    Halasa, Natasha B; Gerber, Michael A; Berry, Andrea A; Anderson, Edwin L; Winokur, Patricia; Keyserling, Harry; Eckard, Allison Ross; Hill, Heather; Wolff, Mark C; McNeal, Monica M; Edwards, Kathryn M; Bernstein, David I

    2015-09-01

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

  17. A nonproliferating parvovirus vaccine vector elicits sustained, protective humoral immunity following a single intravenous or intranasal inoculation.

    Science.gov (United States)

    Palmer, Gene A; Brogdon, Jennifer L; Constant, Stephanie L; Tattersall, Peter

    2004-02-01

    An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th(1) immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4(+) T cells.

  18. Single dose planning for radioiodine-131 therapy of Graves' disease

    International Nuclear Information System (INIS)

    Kita, Tamotsu; Yokoyama, Kunihiko; Kinuya, Seigo; Taki, Junichi; Michigishi, Takatoshi; Tonami, Norihisa

    2004-01-01

    Patients with Graves' disease were studied one year after radioiodine-131 therapy to assess the relationship between the effectiveness of the therapy and the radioiodine doses used. Patients were classified into three groups according to thyroid function as hyperthyroidism, euthyroidism and hypothyroidism at one year after I-131 therapy. In these groups we compared the mean values of dose, dose per thyroid weight calculated with I-123 uptake before the therapy (pre D/W), dose per thyroid weight calculated with therapeutic I-131 uptake (post D/W), and absorbed dose. No significant differences were found between the three groups in terms of dose or pre D/W. The mean values of post D/W and absorbed dose in the non-hyperthyroid (euthyroid and hypothyroid) group were significantly greater than those in the hyperthyroid group. Post D/W of 6.3 MBq/g was a threshold separating the non-hyperthyroid group from the hyperthyroid group. There was no correlation between pre D/W and post D/W; however, the mean post D/W was significantly greater than the mean pre D/W. All patients with pre D/W above 6.3 MBq/g showed non-hyperthyroidism at one year after the radioiodine treatment. No indicators before the radioiodine therapy had significant relationships with the effectiveness of the therapy at one year after the treatment. However, the single therapy planned for setting the pre D/W above 6.3 MBq/g will certainly make the patients non-hyperthyroid. As this proposal of dose planning is based on a small number of patients, further study is needed. (author)

  19. Preclinical evaluation of the saponin derivative GPI-0100 as an immunostimulating and dose-sparing adjuvant for pandemic influenza vaccines

    NARCIS (Netherlands)

    Liu, Heng; Bungener, Laura; ter Veer, Wouter; Coller, Beth-Ann; Wilschut, Jan; Huckriede, Anke

    2011-01-01

    With the current global influenza vaccine production capacity the large demand for vaccines in case of a pandemic can only be fulfilled when antigen dose sparing strategies are employed. Here we used a murine challenge model to evaluate the potential of GPI-0100, a semi-synthetic saponin derivative,

  20. Duration of post-vaccination immunity to yellow fever in volunteers eight years after a dose-response study.

    Science.gov (United States)

    de Menezes Martins, Reinaldo; Maia, Maria de Lourdes S; de Lima, Sheila Maria Barbosa; de Noronha, Tatiana Guimarães; Xavier, Janaina Reis; Camacho, Luiz Antonio Bastos; de Albuquerque, Elizabeth Maciel; Farias, Roberto Henrique Guedes; da Matta de Castro, Thalita; Homma, Akira

    2018-06-27

    In 2009, Bio-Manguinhos conducted a dose-response study with the yellow fever vaccine, administering the vaccine in the usual mean dose of 27,476 IU (full dose, reference) and in tapered doses (10,447 IU, 3013 IU, 587 IU, 158 IU, and 31 IU) by the usual subcutaneous route and usual volume (0.5 mL). Tapered doses were obtained by dilution in the manufacturer's laboratory, and the test batches presented industrial quality. Doses down to 587 IU showed similar immunogenicity to the full dose (27,476, reference), while the 158 IU and 31 IU doses displayed lower immunogenicity. Seropositivity was maintained at 10 months, except in the group that received the 31 IU dose. The current study aims to determine whether yellow fever seropositivity was maintained eight years after YF vaccination in non-revaccinated individuals. According to the current study's results, seropositivity was maintained in 85% of 318 participants and was similar across groups. The findings support the use of the yellow fever vaccine in fractional doses during outbreaks, but each fractional dose should have at least 587 IU. This study also supports the minimum dose required by WHO, 1000 IU. Clinicaltrials.gov NCT 03338231. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Low Dose Vaccination with Attenuated Francisella tularensis Strain SchuS4 Mutants Protects against Tularemia Independent of the Route of Vaccination

    Science.gov (United States)

    Rockx-Brouwer, Dedeke; Chong, Audrey; Wehrly, Tara D.; Child, Robert; Crane, Deborah D.

    2012-01-01

    Tularemia, caused by the Gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease. Interest in tularemia has increased over the last decade due to its history as a biological weapon. In particular, development of novel vaccines directed at protecting against pneumonic tularemia has been an important goal. Previous work has demonstrated that, when delivered at very high inoculums, administration of live, highly attenuated strains of virulent F. tularensis can protect against tularemia. However, lower vaccinating inoculums did not offer similar immunity. One concern of using live vaccines is that the host may develop mild tularemia in response to infection and use of high inoculums may contribute to this issue. Thus, generation of a live vaccine that can efficiently protect against tularemia when delivered in low numbers, e.g. tularemia when delivered at concentrations of approximately 50 or fewer bacteria. Attenuated strains for use as vaccines were selected by their inability to efficiently replicate in macrophages in vitro and impaired replication and dissemination in vivo. Although all strains were defective for replication in vitro within macrophages, protective efficacy of each attenuated mutant was correlated with their ability to modestly replicate and disseminate in the host. Finally, we demonstrate the parenteral vaccination with these strains offered superior protection against pneumonic tularemia than intranasal vaccination. Together our data provides proof of principle that low dose attenuated vaccines may be a viable goal in development of novel vaccines directed against tularemia. PMID:22662210

  2. A single-aliquot OSL protocol using bracketing regenerative doses to accurately determine equivalent doses in quartz

    International Nuclear Information System (INIS)

    Folz, Elise; Mercier, Norbert

    1999-01-01

    In most cases, sediments show inherent heterogeneity in their luminescence behaviours and bleaching histories, and identical aliquots are not available: single-aliquot determination of the equivalent dose (ED) is then the approach of choice and the advantages of using regenerative protocols are outlined. Experiments on five laboratory bleached and dosed quartz samples, following the protocol described by Murray and Roberts (1998. Measurement of the equivalent dose in quartz using a regenerative-dose single aliquot protocol. Radiation Measurements 27, 171-184), showed the hazards of using a single regeneration dose: a 10% variation in the regenerative dose yielded some equivalent dose estimates that differed from the expected value by more than 5%. A protocol is proposed that allows the use of different regenerative doses to bracket the estimated equivalent dose. The measured ED is found to be in excellent agreement with the known value when the main regeneration dose is within 10% of the true equivalent dose

  3. A single-aliquot OSL protocol using bracketing regenerative doses to accurately determine equivalent doses in quartz

    CERN Document Server

    Folz, E

    1999-01-01

    In most cases, sediments show inherent heterogeneity in their luminescence behaviours and bleaching histories, and identical aliquots are not available: single-aliquot determination of the equivalent dose (ED) is then the approach of choice and the advantages of using regenerative protocols are outlined. Experiments on five laboratory bleached and dosed quartz samples, following the protocol described by Murray and Roberts (1998. Measurement of the equivalent dose in quartz using a regenerative-dose single aliquot protocol. Radiation Measurements 27, 171-184), showed the hazards of using a single regeneration dose: a 10% variation in the regenerative dose yielded some equivalent dose estimates that differed from the expected value by more than 5%. A protocol is proposed that allows the use of different regenerative doses to bracket the estimated equivalent dose. The measured ED is found to be in excellent agreement with the known value when the main regeneration dose is within 10% of the true equivalent dose.

  4. Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts.

    Science.gov (United States)

    Tseng, Chih-Wen; Trimble, Cornelia; Zeng, Qi; Monie, Archana; Alvarez, Ronald D; Huh, Warner K; Hoory, Talia; Wang, Mei-Cheng; Hung, Chien-Fu; Wu, T-C

    2009-05-01

    Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination with either vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA vaccination generated significant therapeutic antitumor effects and the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during the second DNA vaccination generated the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy in combination with radiation and CRT/E7(detox) DNA vaccination generate significantly enhanced therapeutic antitumor effects. The clinical implications of the study are discussed.

  5. [Safety and immunogenicity of a 7-valent pneumococcal conjugate vaccine (Prevenar) booster dose in healthy Chinese toddlers].

    Science.gov (United States)

    Li, Rong-cheng; Li, Feng-xiang; Li, Yan-ping

    2009-06-01

    To evaluate the safety and immunogenicity of the booster dose of 7 valent pneumococcal conjugate vaccine (PCV7) to the healthy Chinese toddlers who had received 3 primary doses. Four hundred and eighty-eight Chinese toddlers received a booster dose of PCV7 at age of 12-15 months following a primary series of the vaccine given at ages 3, 4, 5 months separately with Diphtheria Tetanus Acellular Pertussis Combined Vaccine (DTaP) in Group 1 or concurrently with DTaP in Group 2. Following the booster dose immunization, each subject was followed up for 30 days to observe the safety of the vaccine. Blood samples were taken from a subset of subjects prior and post 30 days the booster dose immunization to evaluate immunogenicity. A high proportion of subjects in Group 1 (89%) and Group 2 (91%) remained afebrile after the booster dose. Local reactions to the PCV7 booster dose were generally mild. For each serotype, the rise in GMC (post-/pre-vaccination) showed a statistically significant difference (P<0.0001) between both groups. PCV7 administered as a booster dose is generally safe, well tolerate, and immunogenic in healthy Chinese toddlers.

  6. Safety and efficacy of reduced doses of Brucella melitensis strain Rev. 1 vaccine in pregnant Iranian fat-tailed ewes

    Directory of Open Access Journals (Sweden)

    Mohammad Ebrahimi

    2012-12-01

    Full Text Available Brucellosis is one of the most important zoonotic diseases and is a significant cause of abortion in animals. Brucella melitensis strain Rev. 1 is recommended as the most effective vaccine for small ruminants but the application of full doses in adult animals is restricted. This study was conducted to determine a proper reduced dose of vaccine which confers protection but which is not abortifacient in Iranian fat-tailed sheep. A total of 51 non-vaccinated pregnant ewes were divided into three main groups and several subgroups. Ewes in different groups were vaccinated at different stages of pregnancy and various subgroups were subcutaneously immunised with different quantities of the micro-organism (7.5 × 106, 106, 5 × 105. Ewes again became pregnant a year later and were challenged with the wild-type strain to evaluate the protection conferred. Results revealed that the proportion of vaccination-induced abortions was significantly higher in ewes immunised with 7.5 × 106 Rev. 1 organisms than in those which received 106 or 5 × 105 bacteria. While 80% of non-vaccinated ewes aborted after challenge, none of the vaccinated ewes aborted post-challenge. This study indicated that a reduced dose of Rev. 1 vaccine containing 106 or 5 × 105 live cells could be safely used to induce protection in Iranian fat-tailed sheep at various stages of pregnancy.

  7. Two doses of bovine viral diarrhea virus DNA vaccine delivered by electroporation induce long-term protective immune responses.

    Science.gov (United States)

    van Drunen Littel-van den Hurk, Sylvia; Lawman, Zoe; Snider, Marlene; Wilson, Don; van den Hurk, Jan V; Ellefsen, Barry; Hannaman, Drew

    2013-02-01

    Bovine viral diarrhea virus (BVDV) is a pathogen of major importance in cattle, so there is a need for new effective vaccines. DNA vaccines induce balanced immune responses and are relatively inexpensive and thus promising for both human and veterinary applications. In this study, newborn calves with maternal antibodies were vaccinated intramuscularly (i.m.) with a BVDV E2 DNA vaccine with the TriGrid Delivery System for i.m. delivery (TDS-IM). Two doses of this vaccine spaced 6 or 12 weeks apart were sufficient to induce significant virus-neutralizing antibody titers, numbers of activated T cells, and reduction in viral shedding and clinical presentations after BVDV-2 challenge. In contrast to the placebo-treated animals, the vaccinated calves did not lose any weight, which is an excellent indicator of the well-being of an animal and has a significant economic impact. Furthermore, the interval between the two vaccinations did not influence the magnitude of the immune responses or degree of clinical protection, and a third immunization was not necessary or beneficial. Since electroporation may enhance not only the magnitude but also the duration of immunity after DNA immunization, the interval between vaccination and challenge was extended in a second trial, which showed that two doses of this E2 DNA vaccine again significantly reduced clinical disease against BVDV for several months. These results are promising and support this technology for use against infectious diseases in cattle and large species, including humans, in general.

  8. Immune response in pigs treated with therapeutic doses of enrofloxacin at the time of vaccination against Aujeszky's disease.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Rachubik, Jarosław; Lipowski, Andrzej; Pejsak, Zygmunt

    2015-06-01

    The effect of treatment with enrofloxacin was studied on the postvaccinal immune response in pigs. Forty pigs were used (control not vaccinated (C), control vaccinated (CV), vaccinated, received enrofloxacin (ENRO)). From day -1 to day 3 pigs from ENRO group received enrofloxacin at the recommended dose. Pigs from ENRO and CV groups were vaccinated twice against Aujeszky's disease virus (ADV). There was a significant delay in the production of humoral response of enrofloxacin dosed pigs when compared with CV group. Moreover, in ENRO group the significant decrease in IFN-γ production and significantly lower values of stimulation index after ADV restimulation was noted, as compared with CV group. The secretion of IL-6, IL-10 and TNF-α by PBMC after recall stimulation was also affected in ENRO group. The results indicate that enrofloxacin, in addition to its antimicrobial properties, possess significant immunomodulatory effects and may alter the immune response to vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Haaft, Peter ten; Heeney, Jonathan; Ueberla, Klaus

    2003-01-01

    To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 10 3 to 10 4 copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV

  10. Single dose toxicity and biodistribution studies of [18F] fluorocholine

    International Nuclear Information System (INIS)

    Campos, Danielle C.; Santos, Priscilla F.; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D.

    2013-01-01

    [ 18 F]Fluorocholine ( 18 FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of 18 FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of 18 FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  11. Single-dose radiotherapy for painful bone metastases

    International Nuclear Information System (INIS)

    Kal, H.B.

    1999-01-01

    Background: External beam radiotherapy is frequently applied for palliative treatment of painful bone lesions with a variety of fractionation schemes. There is a continuous interest to administer only 1 or a few dose fractions for inducing pain relief. Methods: A review of the literature was made with the aim to determine whether a treatment can be deduced that is simple and effective. The linear-quadratic (L-Q) concept was applied to compare reported therapy schemes which each other for the iso-effect pain relief. Results: Single-dose and fractionated radiotherapy resulted in partial or complete pain relief in about 80% of the patients. Complete responses have been observed in about 43% of the patients. For patients responding to treatment, the duration of pain relief is at least 3 to 4 months with reported duration of up to 1 year or even longer. Conclusion: Based on this review of literature data concerning randomized trials a treatment with a single dose of 8 Gy is effective for inducing pain relief. (orig.) [de

  12. A single dose desensitization for summer hay fever. Results of a double blind study-1988.

    Science.gov (United States)

    Fell, P; Brostoff, J

    1990-01-01

    A new type of desensitising vaccine, enzyme potentiated was subjected to a double-blind randomised study during the hay fever season. The vaccine is a convenient single injection given in March and the results show good protection throughout the grass pollen season.

  13. Expected cost effectiveness of high-dose trivalent influenza vaccine in US seniors.

    Science.gov (United States)

    Chit, Ayman; Roiz, Julie; Briquet, Benjamin; Greenberg, David P

    2015-01-29

    Seniors are particularly vulnerable to complications resulting from influenza infection. Numerous influenza vaccines are available to immunize US seniors, and practitioners must decide which product to use. Options include trivalent and quadrivalent standard-dose inactivated influenza vaccines (IIV3 and IIV4 respectively), as well as a high-dose IIV3 (HD). Our research examines the public health impact, budget impact, and cost-utility of HD versus IIV3 and IIV4 for immunization of US seniors 65 years of age and older. Our model was based on US influenza-related health outcome data. Health care costs and vaccine prices were obtained from the Centers for Medicare and Medicaid Services. Efficacies of IIV3 and IIV4 were estimated from various meta-analyses of IIV3 efficacy. The results of a head-to-head randomized controlled trial of HD vs. IIV3 were used to estimate relative efficacy of HD. Conservatively, herd protection was not considered. Compared to IIV3, HD would avert 195,958 cases of influenza, 22,567 influenza-related hospitalizations, and 5423 influenza-related deaths among US seniors. HD generates 29,023 more Quality Adjusted Life Years (QALYs) and a net societal budget impact of $154 million. The Incremental Cost Effectiveness Ratio (ICER) for this comparison is $5299/QALY. 71% of the probabilistic sensitivity analysis (PSA) simulations were seniors. Our conclusions were robust in the face of sensitivity analyses. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Compliance with birth dose of Hepatitis B vaccine in high endemic and hard to reach areas in the Colombian amazon: results from a vaccination survey.

    Science.gov (United States)

    Choconta-Piraquive, Luz Angela; De la Hoz-Restrepo, Fernando; Sarmiento-Limas, Carlos Arturo

    2016-07-21

    Hepatitis B vaccination was introduced into the Expanded Program of Immunization in Colombia in 1992, in response to WHO recommendations on hepatitis B immunization. Colombia is a low endemic country for Hepatitis B virus infection (HBV) but it has several high endemic areas like the Amazon basin where more than 70 % of adults had been infected. A cross- sectional study was carried out in three rural areas of the Colombian Amazon to evaluate compliance with the recommended schedule for hepatitis B vaccine in Colombian children (one monovalent dose given in the first 24 h after birth + 3 doses of a pentavalent containing Hepatitis B. (DPT + Hib + Hep B). A household survey was conducted in order to collect vaccination data from children aged from 6 months to studied, 79 % received a monovalent dose of hepatitis B vaccine, but only 30.7 % were vaccinated in the first 24 h after birth. This proportion did not increase by age or subsequent birth cohorts. Coverage with three doses of a DTP-Hib-HepB vaccine was 98 %, but most children did not receive them according to the recommended schedule. Being born in a health facility was the strongest predictor of receiving a timely birth dose. This study suggests that more focused strategies on improving compliance with hepatitis B birth dose should be implemented in rural areas of the Amazon, if elimination of perinatal transmission of HBV is to be achieved. Increasing the proportion of newborns delivered at health facilities should be one of the priorities to reach that goal.

  15. Human Phase 1 trial of low-dose inactivated seasonal influenza vaccine formulated with Advax™ delta inulin adjuvant.

    Science.gov (United States)

    Gordon, David L; Sajkov, Dimitar; Honda-Okubo, Yoshikazu; Wilks, Samuel H; Aban, Malet; Barr, Ian G; Petrovsky, Nikolai

    2016-07-19

    Influenza vaccines are usually non-adjuvanted but addition of adjuvant may improve immunogenicity and permit dose-sparing, critical for vaccine supply in the event of an influenza pandemic. The aim of this first-in-man study was to determine the effect of delta inulin adjuvant on the safety and immunogenicity of a reduced dose seasonal influenza vaccine. Healthy male and female adults aged 18-65years were recruited to participate in a randomized controlled study to compare the safety, tolerability and immunogenicity of a reduced-dose 2007 Southern Hemisphere trivalent inactivated influenza vaccine formulated with Advax™ delta inulin adjuvant (LTIV+Adj) when compared to a full-dose of the standard TIV vaccine which does not contain an adjuvant. LTIV+Adj provided equivalent immunogenicity to standard TIV vaccine as assessed by hemagglutination inhibition (HI) assays against each vaccine strain as well as against a number of heterosubtypic strains. HI responses were sustained at 3months post-immunisation in both groups. Antibody landscapes against a large panel of H3N2 influenza viruses showed distinct age effects whereby subjects over 40years old had a bimodal baseline HI distribution pattern, with the highest HI titers against the very oldest H3N2 isolates and with a second HI peak against influenza isolates from the last 5-10years. By contrast, subjects >40years had a unimodal baseline HI distribution with peak recognition of H3N2 isolates from approximately 20years ago. The reduced dose TIV vaccine containing Advax adjuvant was well tolerated and no safety issues were identified. Hence, delta inulin may be a useful adjuvant for use in seasonal or pandemic influenza vaccines. Australia New Zealand Clinical Trial Registry: ACTRN12607000599471. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Immune responses after fractional doses of inactivated poliovirus vaccine using newly developed intradermal jet injectors: a randomized controlled trial in Cuba.

    Science.gov (United States)

    Resik, Sonia; Tejeda, Alina; Mach, Ondrej; Fonseca, Magile; Diaz, Manuel; Alemany, Nilda; Garcia, Gloria; Hung, Lai Heng; Martinez, Yenisleydis; Sutter, Roland

    2015-01-03

    The World Health Organization recommends that, as part of the new polio endgame, a dose of inactivated poliovirus vaccine (IPV) be introduced by the end of 2015 in all countries using only oral poliovirus vaccine (OPV). Administration of fractional dose (1/5th of full dose) IPV (fIPV) intradermally may reduce costs, but its administration is cumbersome with BCG needle and syringe. We evaluated performance of two newly developed intradermal-only jet injectors and compared the immune response induced by fIPV with that induced by full-dose IPV. Children between 12 and 20 months of age, who had previously received two doses of OPV, were enrolled in Camaguey, Cuba. Subjects received a single dose of IPV (either full-dose IPV intramuscularly with needle and syringe or fIPV intradermally administered with one of two new injectors or with BCG needle or a conventional needle-free injector). Serum was tested for presence of poliovirus neutralizing antibodies on day 0 (pre-IPV) and on days 3, 7 and 21 (post-vaccination). Complete data were available from 74.2% (728/981) subjects. Baseline median antibody titers were 713, 284, and 113 for poliovirus types 1, 2, and 3, respectively. Seroprevalence at study end were similar across the intervention groups (≥ 94.8%). The immune response induced with one new injector was similar to BCG needle and to the conventional injector; and superior to the other new injector. fIPV induced significantly lower boosting response compared to full-dose IPV. No safety concerns were identified. One of the two new injectors demonstrated its ability to streamline intradermal fIPV administration, however, further investigations are needed to assess the potential contribution of fIPV in the polio endgame plan. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Effectiveness of one dose of mumps vaccine against clinically diagnosed mumps in Guangzhou, China, 2006-2012.

    Science.gov (United States)

    Fu, Chuanxi; Xu, Jianxiong; Cai, Yuanjun; He, Qing; Zhang, Chunhuan; Chen, Jian; Dong, Zhiqiang; Hu, Wensui; Wang, Hui; Zhu, Wei; Wang, Ming

    2013-12-01

    Although mumps-containing vaccines were introduced in China in 1990s, mumps continues to be a public health concern due to the lack of decline in reported mumps cases. To assess the mumps vaccine effectiveness (VE) in Guangzhou, China, we performed a 1:1 matched case-control study. Among children in Guangzhou aged 8 mo to 12 y during 2006 to 2012, we matched one healthy child to each child with clinically diagnosed mumps. Cases with clinically diagnosed mumps were identified from surveillance sites system and healthy controls were randomly sampled from the Children's Expanded Programmed Immunization Administrative Computerized System in Guangzhou. Conditional logistic regression was used to calculate VE. We analyzed the vaccination information for 1983 mumps case subjects and 1983 matched controls and found that the overall VE for 1 dose of mumps vaccine, irrespective of the manufacture, was 53.6% (95% confidence interval [CI], 41.0-63.5%) to children aged 8 mo to 12 y. This post-marketing mumps VE study found that immunization with one dose of the mumps vaccine confers partial protection against mumps disease. Evaluation of the VE for the current mumps vaccines, introduction of a second dose of mumps vaccine, and assessment of modifications to childhood immunization schedules is essential.

  18. Effectiveness of one dose of mumps vaccine against clinically diagnosed mumps in Guangzhou, China, 2006–2012

    Science.gov (United States)

    Fu, Chuanxi; Xu, Jianxiong; Cai, Yuanjun; He, Qing; Zhang, Chunhuan; Chen, Jian; Dong, Zhiqiang; Hu, Wensui; Wang, Hui; Zhu, Wei; Wang, Ming

    2013-01-01

    Although mumps-containing vaccines were introduced in China in 1990s, mumps continues to be a public health concern due to the lack of decline in reported mumps cases. To assess the mumps vaccine effectiveness (VE) in Guangzhou, China, we performed a 1:1 matched case-control study. Among children in Guangzhou aged 8 mo to 12 y during 2006 to 2012, we matched one healthy child to each child with clinically diagnosed mumps. Cases with clinically diagnosed mumps were identified from surveillance sites system and healthy controls were randomly sampled from the Children’s Expanded Programmed Immunization Administrative Computerized System in Guangzhou. Conditional logistic regression was used to calculate VE. We analyzed the vaccination information for 1983 mumps case subjects and 1983 matched controls and found that the overall VE for 1 dose of mumps vaccine, irrespective of the manufacture, was 53.6% (95% confidence interval [CI], 41.0–63.5%) to children aged 8 mo to 12 y. This post-marketing mumps VE study found that immunization with one dose of the mumps vaccine confers partial protection against mumps disease. Evaluation of the VE for the current mumps vaccines, introduction of a second dose of mumps vaccine, and assessment of modifications to childhood immunization schedules is essential. PMID:23955378

  19. EVALUATION OF OIL BASED AVIAN INFLUENZA VACCINE (H5NI PREPARED WITH DIFFERENT CONCENTRATIONS OF ADJUVANT

    Directory of Open Access Journals (Sweden)

    M. IQBAL, M. NISAR, ANWARUL-HAQ, S. NOOR AND Z. J. GILL

    2008-12-01

    Full Text Available Bird flu vaccine from H5N1 strain of avian influenza virus was prepared with two concentrations of adjuvant (Montanide ISA 70MVG. Two vaccines (I and II were prepared containing 50 and 60% Montanide, respectively. Immune response of both the vaccines as single, as well as booster, dose was evaluated in layer birds through haemagglutination inhibition test. Single dose of both vaccines showed poor immune response, while booster dose gave better response with both the vaccines. However, the vaccine prepared with 60% Montanide provided better immune response compared with the vaccine containing 50% montanide.

  20. Single-Dose Lignocaine-Based Blood Cardioplegia in Single Valve Replacement Patients

    Directory of Open Access Journals (Sweden)

    Jaydip Ramani

    Full Text Available Abstract OBJECTIVE: Myocardial protection is the most important in cardiac surgery. We compared our modified single-dose long-acting lignocaine-based blood cardioplegia with short-acting St Thomas 1 blood cardioplegia in patients undergoing single valve replacement. METHODS: A total of 110 patients who underwent single (aortic or mitral valve replacement surgery were enrolled. Patients were divided in two groups based on the cardioplegia solution used. In group 1 (56 patients, long-acting lignocaine based-blood cardioplegia solution was administered as a single dose while in group 2 (54 patients, standard St Thomas IB (short-acting blood-based cardioplegia solution was administered and repeated every 20 minutes. All the patients were compared for preoperative baseline parameters, intraoperative and all the postoperative parameters. RESULTS: We did not find any statistically significant difference in preoperative baseline parameters. Cardiopulmonary bypass time were 73.8±16.5 and 76.4±16.9 minutes (P=0.43 and cross clamp time were 58.9±10.3 and 66.3±11.2 minutes (P=0.23 in group 1 and group 2, respectively. Mean of maximum inotrope score was 6.3±2.52 and 6.1±2.13 (P=0.65 in group 1 and group 2, respectively. We also did not find any statistically significant difference in creatine-phosphokinase-MB (CPK-MB, Troponin-I levels, lactate level and cardiac functions postoperatively. CONCLUSION: This study proves the safety and efficacy of long-acting lignocaine-based single-dose blood cardioplegia compared to the standard short-acting multi-dose blood cardioplegia in patients requiring the single valve replacement. Further studies need to be undertaken to establish this non-inferiority in situations of complex cardiac procedures especially in compromised patients.

  1. Dose-response effects in immunizations with keyhole limpet haemocyanin and rabies vaccine: shift in some immunodeficiency states

    NARCIS (Netherlands)

    Korver, K.; Boeschoten, E. W.; Krediet, R. T.; van Steenis, G.; Schellekens, P. T.

    1987-01-01

    We investigated the primary antibody response to the antigens keyhole limpet haemocyanin (KLH) and rabies vaccine (RV). Eighty-one healthy volunteers were injected with nine doses of KLH (ranging from 10 to 2500 micrograms) and 66 volunteers with six doses of RV (ranging from 17 to 680 micrograms

  2. Single dose oral flurbiprofen for acute postoperative pain in adults

    Science.gov (United States)

    Sultan, Asquad; McQuay, Henry J; Moore, R Andrew; Derry, Sheena

    2014-01-01

    Background Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions. The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25

  3. Efficacy, immunogenicity, and safety of two doses of a tetravalent rotavirus vaccine RRV-TV in Ghana with the first dose administered during the neonatal period.

    Science.gov (United States)

    Armah, George E; Kapikian, Albert Z; Vesikari, Timo; Cunliffe, Nigel; Jacobson, Robert M; Burlington, D Bruce; Ruiz, Leonard P

    2013-08-01

    Oral rhesus/rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) was licensed in 1998 but withdrawn in 1999 due to a rare association with intussusception, which occurred disproportionately in infants receiving their first dose at ≥90 days of age. This study examined RRV-TV for the prevention of rotavirus gastroenteritis (RV-GE) in Ghana, West Africa, with infants receiving the first dose during the neonatal period and the second before 60 days of age. In a double-blinded, randomized, placebo-controlled trial in Navrongo, Ghana, we recruited neonates to receive 2 doses of RRV-TV or placebo and followed them to age 12 months. In the intention-to-treat population of 998 infants, we measured a vaccine efficacy of 63.1% against RV-GE of any severity associated with any of the 4 serotypes represented in the vaccine and 60.7% against RV-GE associated with any rotavirus serotype. RRV-TV in a 2-dose schedule with the first dose during the neonatal period is efficacious in preventing RV-GE in rural Ghana. Neonatal dosing results in early protection and may be the optimum schedule to avoid or significantly reduce intussusception, now reported to be associated in international settings with the 2 most widely marketed, licensed, live virus, oral rotavirus vaccines.

  4. DNA vaccination of rainbow trout against viral hemorrhagic septicemia virus: A dose-response and time-course study

    DEFF Research Database (Denmark)

    Lorenzen, Ellen; Einer-Jensen, Katja; Martinussen, T.

    2000-01-01

    Viral hemorrhagic septicemia (VHS) in rainbow trout Oncorhynchus mykiss is caused by VHS virus (VHSV), which belongs to the rhabdovirus family. Among the different strategies for immunizing fish with a recombinant vaccine, genetic immunization has recently proven to be highly effective. To further...... investigate the potential for protecting fish against VHS by DNA vaccination, experiments were conducted to determine the amount of plasmid DNA needed for induction of protective immunity. The time to onset of immunity and the duration of protection following administration of a protective vaccine dose were...... serologically different from the isolate used for vaccine development. Following administration of 1 mug of a DNA vaccine, significant protection against VHS was observed in the fish as early as 8 d postvaccination. At 168 d postvaccination, the fish had increased in size by a factor of 10 and protection...

  5. Low dose vaccination with attenuated Francisella tularensis strain SchuS4 mutants protects against tularemia independent of the route of vaccination.

    Directory of Open Access Journals (Sweden)

    Dedeke Rockx-Brouwer

    Full Text Available Tularemia, caused by the gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease. Interest in tularemia has increased over the last decade due to its history as a biological weapon. In particular, development of novel vaccines directed at protecting against pneumonic tularemia has been an important goal. Previous work has demonstrated that, when delivered at very high inoculums, administration of live, highly attenuated strains of virulent F. tularensis can protect against tularemia. However, lower vaccinating inoculums did not offer similar immunity. One concern of using live vaccines is that the host may develop mild tularemia in response to infection and use of high inoculums may contribute to this issue. Thus, generation of a live vaccine that can efficiently protect against tularemia when delivered in low numbers, e.g. <100 organisms, may address this concern. Herein we describe the ability of three defined, attenuated mutants of F. tularensis SchuS4, deleted for FTT0369c, FTT1676, or FTT0369c and FTT1676, respectively, to engender protective immunity against tularemia when delivered at concentrations of approximately 50 or fewer bacteria. Attenuated strains for use as vaccines were selected by their inability to efficiently replicate in macrophages in vitro and impaired replication and dissemination in vivo. Although all strains were defective for replication in vitro within macrophages, protective efficacy of each attenuated mutant was correlated with their ability to modestly replicate and disseminate in the host. Finally, we demonstrate the parenteral vaccination with these strains offered superior protection against pneumonic tularemia than intranasal vaccination. Together our data provides proof of principle that low dose attenuated vaccines may be a viable goal in development of novel vaccines directed against tularemia.

  6. SINGLE-DOSE VERSUS 3-DAY PROPHYLAXIS WITH CIPROFLOXACIN IN TRANSURETHRAL SURGERY - A CLINICAL-TRIAL

    NARCIS (Netherlands)

    BIJL, W; JANKNEGT, RA

    1993-01-01

    in 235 patients who underwent transurethral surgery, perioperative oral ciprofloxacin prophylaxis was given as a single dose 500 mg versus a 3-day regimen. Out of 180 evaluable patients, 84 received a single dose and 96 received a 3-day course. In the single dose prophylaxis group there were 5

  7. Single dose oral piroxicam for acute postoperative pain

    Science.gov (United States)

    Moore, R Andrew; Edwards, Jayne; Loke, Yoon; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 2, 2000. Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. Objectives To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. Search methods Published studies were identified from systematic searching of MEDLINE, Biological Abstracts, EMBASE, CENTRAL and the Oxford Pain Relief Database in December 2007. Additional studies were identified from the reference lists of retrieved reports. Selection criteria The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult participants, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. Data collection and analysis Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-treat-to-harm (NNH) were calculated. Main results In this update no further studies were found. The original search identified three studies (141 participants) which compared oral piroxicam 20 mg with placebo and

  8. The costs of home delivery of a birth dose of hepatitis B vaccine in a prefilled syringe in Indonesia.

    OpenAIRE

    Levin, Carol E.; Nelson, Carib M.; Widjaya, Anton; Moniaga, Vanda; Anwar, Chairiyah

    2005-01-01

    OBJECTIVE: To provide global policy-makers with decision-making information for developing strategies for immunization of infants with a birth dose of hepatitis B vaccine, this paper presents a retrospective cost analysis, conducted in Indonesia, of delivering this vaccine at birth using the Uniject prefill injection device. METHODS: Incremental costs or cost savings associated with changes in the hepatitis B immunization programme were calculated using sensitivity analysis to vary the estima...

  9. Assessment of vaccination with schistosomules attenuated by using different doses of γ-radiation on experimental schistosomiasis mansoni

    International Nuclear Information System (INIS)

    Mohamed, E.N.H.

    2009-01-01

    Current strategies for the control of schistosomiasis are based primarily on chemotherapy but successful vaccination against infection has been also demonstrated in several host parasite models.The present study was designed to asses the immunogenic effects of the vaccination with autogenic targets in the form of schistosomula attenuated by different doses of γ-radiation (15, 20, 25 kilo rad) in mice challenged with S. mansoni cercariae as regard parasitological, histological, biochemical and immunological aspects.

  10. The Economics of Vaccinating or Dosing Cattle against Disease: A Simple Linear Cost-Benefit Model with Modifications

    OpenAIRE

    Tisdell, Clem; Ramsay, Gavin

    1995-01-01

    Outlines a simple linear cost-benefit model for determining whether it is economic at the farm-level to vaccinate or dose a batch of livestock against a disease. This model assumes that total benefits and costs are proportional to the number of animals vaccinated. This model is then modified to allow for the possibility of programmes of vaccination or disease prevention involving start-up costs which increase, but at a decreasing rate with batch size or with the size of the herd to be vaccina...

  11. [Safety data of the new, reduced-dose influenza vaccine FluArt after its first season on the market].

    Science.gov (United States)

    Vajó, Péter; Gyurján, Orsolya; Szabó, Ágnes Mira; Kalabay, László; Vajó, Zoltán; Torzsa, Péter

    2017-12-01

    The currently licensed seasonal influenza vaccines contain split, subunit or whole virions, typically in amounts of 15 µg hemagglutinin per virus strain for adult and up to 60 µg in elderly patients. The present study reports safety data of the newly licensed, reduced dose vaccine with 6 µg of hemagglutinin per strain produced by Fluart (Hungary) after its first season on the market. The main objective of enhanced safety surveillance was to detect a potential increase in reactogenicity and allergic events that is intrinsic to the product in near real-time in the earliest vaccinated cohorts. The study methods were based on the Interim guidance on enhanced safety surveillance for seasonal influenza vaccines in the EU by the European Medicines Agency. We used the Fisher exact test with 95% confidence intervals. We studied 587 patients and detected a total 24 adverse events, all of which have already been known during the licensing studies of the present vaccine. The frequencies of the adverse events were not different from what had been seen with the previously licensed 15 µg vaccine. Based on the results, the authors conclude that the new, reduced dose vaccine FluArt is safe and tolerable. Orv Hetil. 2017; 158(49): 1953-1959.

  12. No effect of an additional early dose of measles vaccine on hospitalization or mortality in children

    DEFF Research Database (Denmark)

    Schoeps, Anja; Nebié, Eric; Fisker, Ane Baerent

    2018-01-01

    Background: Non-specific effects (NSEs) of vaccines have increasingly gained attention in recent years. Recent studies suggest that live vaccines, such as measles vaccine (MV), have beneficial effects on health, while inactivated vaccines, such as the diphtheria-tetanus-pertussis (DTP) vaccine, m...

  13. Single-dose Rituximab Therapy for Refractory Idiopathic Membranous Nephropathy: A Single-center Experience

    OpenAIRE

    Katsuno, Takayuki; Ozaki, Takenori; Kim, Hangsoo; Kato, Noritoshi; Suzuki, Yasuhiro; Akiyama, Shinichi; Ishimoto, Takuji; Kosugi, Tomoki; Tsuboi, Naotake; Ito, Yasuhiko; Maruyama, Shoichi

    2017-01-01

    To date, a recognized treatment for refractory membranous nephropathy (MN) has not been established. Recently, several reports have indicated the efficacy of rituximab as a novel treatment option. However, only a few published accounts exist of rituximab therapy for idiopathic MN (IMN) in the Asian population. We present the cases of three IMN patients who were treated with single-dose rituximab after they showed no response to conventional therapies, including corticosteroids, cyclosporine, ...

  14. Single dose pharmacokinetics of fenspiride hydrochloride: phase I clinical trial.

    Science.gov (United States)

    Montes, B; Catalan, M; Roces, A; Jeanniot, J P; Honorato, J M

    1993-01-01

    The absolute bioavailability of fenspiride has been studied in twelve healthy volunteers. It was administered IV and orally in single doses of 80 mg fenspiride hydrochloride according to a randomised crossover pattern. Following IV administration, the plasma clearance of fenspiride was about 184 ml.min-1, and its apparent volume of distribution was moderately large (215 l). When given orally as a tablet, fenspiride exhibited fairly slow ab- sorption; the maximum plasma concentration (206 ng.ml-1) was achieved 6 h after administration. The absolute bioavailability was almost complete (90%). The tablet had slow release characteristics. The elimination half-life obtained from the plasma data was 14 to 16 h independent of the route of administration.

  15. Hematological changes after single large dose half-body irradiation

    International Nuclear Information System (INIS)

    Herrmann, T.; Friedrich, S.; Jochem, I.; Eberhardt, H.J.; Koch, R.; Knorr, A.

    1981-01-01

    The determination of different peripheral blood parameters aimed at the study of side effects on the hematological cellular system following a 5 - 8 Gy single large dose half-body irradiation in 20 patients. Compared to the initial values the leukocytes between the 6. and 14., the thrombocytes between the 14. and 21. postirradiation day as well as the lymphocytes between 3 hours and 4 weeks postirradiation were significantly decreased without exhibiting complications such as hemorrhages or infections. The hemoglobin, hematocrit and reticulocyte values revealed but a slight decrease normalized within a 28 days postirradiation period. Transfusions were necessary when a tumor-caused anemia was present prior to irradiation. Changes in serum activity of aminotransferases and lactate dehydrogenase occured during the first hours after irradiation and were due to enzyme release from destroyed tumor cells

  16. High-level immunogenicity is achieved vaccine with adjuvanted pandemic H1N1(2009) and improved with booster dosing in a randomized trial of HIV-infected adults.

    Science.gov (United States)

    Cooper, Curtis; Klein, Marina; Walmsley, Sharon; Haase, David; MacKinnon-Cameron, Donna; Marty, Kimberley; Li, Yan; Smith, Bruce; Halperin, Scott; Law, Barb; Scheifele, David

    2012-01-01

    More severe influenza disease and poor vaccine immunogenicity in HIV-infected patients necessitate improved immunization strategies to maximize vaccine efficacy. A phase III, randomized trial was conducted at 4 Canadian sites. Two dosing strategies (standard dose vs standard dose plus booster on day 21) were assessed in HIV patients aged 20 to 59 years during the H1N1(2009) pandemic. A single antigen, inactivated split adjuvanted (AS03(A)) influenza vaccine (Arepanrix) was utilized. Serum hemagglutination inhibition (HAI) titres were assessed at days 21 and 42 and at month 6. 150 participants received at least one injection. Baseline parameters were similar between groups: 83% male, 85% on HAART, median CD4 = 519 cells/mm(3), 84% with HIV RNA < 50 copies/mL. At day 21, seroprotection (HAI ≥1:40) was achieved in 80% (95% CI, 70-89) of participants. Seroconversion occurred in 74% (63-85). Seroprotection and seroconversion were further improved in those randomized to booster dosing: day 42, 94% (85-98) versus 73% (60-83) (P < .01) and 86% (75-93) versus 66% (5-77) (P = .01). Seroprotec-tion was retained in 40% (28-54) of recipients at month 6 with trends toward greater retention of immunity in booster recipients. High-level immunogenicity was achieved with a single dose of this adjuvanted vaccine. Immunogenicity was further improved with booster dosing. Use of this adjuvanted vaccine and booster represent an important approach to increasing immunogenicity in this vaccine hypo-responsive population.

  17. Neonatal Immunization with a Single IL-4/Antigen Dose Induces Increased Antibody Responses after Challenge Infection with Equine Herpesvirus Type 1 (EHV-1 at Weanling Age.

    Directory of Open Access Journals (Sweden)

    Bettina Wagner

    Full Text Available Neonatal foals respond poorly to conventional vaccines. These vaccines typically target T-helper (Th cell dependent B-cell activation. However, Th2-cell immunity is impaired in foals during the first three months of life. In contrast, neonatal basophils are potent interleukin-4 (IL-4 producers. The purpose of this study was to develop a novel vaccine triggering the natural capacity of neonatal basophils to secrete IL-4 and to evaluate if vaccination resulted in B-cell activation and antibody production against EHV-1 glycoprotein C (gC. Neonatal vaccination was performed by oral biotinylated IgE (IgE-bio treatment at birth followed by intramuscular injection of a single dose of streptavidin-conjugated gC/IL-4 fusion protein (Sav-gC/IL-4 for crosslinking of receptor-bound IgE-bio (group 1. Neonates in group 2 received the intramuscular Sav-gC/IL-4 vaccine only. Group 3 remained non-vaccinated at birth. After vaccination, gC antibody production was not detectable. The ability of the vaccine to induce protection was evaluated by an EHV-1 challenge infection after weaning at 7 months of age. Groups 1 and 2 responded to EHV-1 infection with an earlier onset and overall significantly increased anti-gC serum antibody responses compared to control group 3. In addition, group 1 weanlings had a decreased initial fever peak after infection indicating partial protection from EHV-1 infection. This suggested that the neonatal vaccination induced a memory B-cell response at birth that was recalled at weanling age after EHV-1 challenge. In conclusion, early stimulation of neonatal immunity via the innate arm of the immune system can induce partial protection and increased antibody responses against EHV-1.

  18. Observational study of vaccine efficacy 24 years after the start of hepatitis B vaccination in two Gambian villages: no need for a booster dose.

    Directory of Open Access Journals (Sweden)

    Maimuna Mendy

    Full Text Available To determine the duration of protection from hepatitis B vaccine given in infancy and early childhood and asses risk factors for HBV infection and chronic infection.In 1984 infant HBV vaccination was started in two Gambian villages. Cross sectional serological surveys have been undertaken every 4 years to determine vaccine efficacy. In the current survey 84.6% of 1508 eligible participants aged 1-28 years were tested. A spouse study was conducted in females (aged 14 years and above and their male partners.Vaccine efficacy against chronic infection with hepatitis B virus was 95.1% (95% confidence interval 91.5% to 97.1%, which did not vary significantly between age groups or village. Efficacy against infection was 85.4% (82.7% to 87.7%, falling significantly with age. Concentrations of hepatitis B antibody fell exponentially with age varying according to peak response: 20 years after vaccination only 17.8% (95% CI 10.1-25.6 of persons with a low peak response (10-99 mIU/ml had detectable HBs antibody compared to 27% (21.9% to 32.2% of those with a high peak response (>999 mIU/ml. Time since vaccination and a low peak response were the strongest risk factors for HBV infections; males were more susceptible, marriage was not a significant risk for females. Hepatitis B DNA was not detected after infection, which tested soley core antibody positive. An undetectable peak antibody response of <10 mIU/ml and a mother who was hepatitis B e antigen positive were powerful risk factors for chronic infection.Adolescents and young adults vaccinated in infancy are at increased risk of hepatitis B infection, but not chronic infection. Married women were not at increased risk. There is no compelling evidence for the use of a booster dose of HBV vaccine in The Gambia.

  19. Low doses of flagellin-L2 multimer vaccines protect against challenge with diverse papillomavirus genotypes.

    Science.gov (United States)

    Kalnin, Kirill; Tibbitts, Timothy; Yan, Yanhua; Stegalkina, Svetlana; Shen, Lihua; Costa, Victor; Sabharwal, Robert; Anderson, Stephen F; Day, Patricia M; Christensen, Neil; Schiller, John T; Jagu, Subhashini; Roden, Richard B S; Almond, Jeffrey; Kleanthous, Harold

    2014-06-12

    Genetically modified bacterial flagellin (Fla), a Toll-like receptor-5 (TLR5) ligand, was evaluated as a fusion partner for human papillomavirus (HPV) L2-based immunogens in two animal challenge models; either cutaneous inoculation of rabbits with HPV 'quasivirions' containing cottontail rabbit papillomavirus (CRPV) genomes that induce warts, or intra-vaginal inoculation of mice with HPV 'pseudovirions' encapsidating a luciferase reporter plasmid and measurement of bioluminescence to determine infectivity. An Escherichia coli production system was developed for flagellin-L2 (Fla-L2) fusions containing either monomeric HPV-16 L2 a.a. 11(×11-200) or oligomeric L2 comprising a fusion of the a.a. 11-88 peptides of five (Fla∼5×11-88) or eight (Fla∼8×11-88) genital HPV types. Immunogenicity and bioactivity of Fla-L2 constructs were assessed using an in vitro neutralization and cell-based TLR-5 binding assay, respectively. Efficacy was evaluated following active immunization of rabbits or mice administered 3 intramuscular doses of Fla-L2 recombinants without exogenous adjuvant, followed by challenge. In addition, passive immunization studies of naïve rabbits with serial dilutions of pooled immune sera were used to determine End-Point Protection Titers (EPPT) for each formulation against a broader spectrum of HPV quasivirions. Efficacy was assessed for up to 10 weeks on the basis of wart volume induced following challenge and results compared to licensed L1-VLP vaccines (Gardasil and Cervarix). Following active immunization at doses as low as 1 μg, Fla-L2 fusions afforded complete protection against infection (mice) and disease (rabbits) following either homologous or heterologous HPV challenge. Passive immunization with anti-L2 immune sera discriminated between the different vaccine candidates under evaluation, demonstrated the protective role of antibody and suggested the superiority of this oligomeric L2-TLR5 agonist fusion approach compared to L1-based

  20. Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants.

    Science.gov (United States)

    Araujo, Eliete C; Clemens, Sue Ann C; Oliveira, Consuelo S; Justino, Maria Cleonice A; Rubio, Pilar; Gabbay, Yvone B; da Silva, Veronilce B; Mascarenhas, Joana D P; Noronha, Vânia L; Clemens, Ralf; Gusmão, Rosa Helena P; Sanchez, Nervo; Monteiro, Talita Antônia F; Linhares, Alexandre C

    2007-01-01

    To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of >or= 11 defined as severe GE. The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain. RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

  1. Interim Canadian recommendations for the use of a fractional dose of yellow fever vaccine during a vaccine shortage

    Science.gov (United States)

    2016-01-01

    Summary This statement outlines interim recommendations intended for use during yellow fever vaccine shortages only. The recommendations differ from the standard recommendations for yellow fever vaccination in the Canadian Immunization Guide and in the Committee to Advise on Tropical Medicine and Travel (CATMAT) Statement for Travellers and Yellow Fever. PMID:29770023

  2. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa

    DEFF Research Database (Denmark)

    Theander, Thor Grundtvig; Lusingu, John Peter Andrea

    2015-01-01

    and a booster dose at month 20 (R3R group); three doses of RTS,S/AS01 and a dose of comparator vaccine at month 20 (R3C group); or a comparator vaccine at months 0, 1, 2, and 20 (C3C [control group]). Participants were followed up until Jan 31, 2014. Cases of clinical and severe malaria were captured through......, the vaccine has the potential to make a substantial contribution to malaria control when used in combination with other effective control measures, especially in areas of high transmission. FUNDING: GlaxoSmithKline Biologicals SA and the PATH Malaria Vaccine Initiative....

  3. Demonstration of 1-year duration of immunity for attenuated Bordetella bronchiseptica vaccines in dogs.

    Science.gov (United States)

    Lehar, Craig; Jayappa, Huchappa; Erskine, Jason; Brown, Alicia; Sweeney, Diane; Wassmoen, Terri

    2008-01-01

    Three groups of healthy dogs with low antibody titers to Bordetella bronchiseptica (Bb), canine parainfluenza virus (CPI), and canine adenovirus type 2 (CAV-2) were used in this study. One group was vaccinated with a single dose of monovalent attenuated Bb vaccine and one group with a trivalent vaccine containing attenuated Bb, CPI, and CAV-2; dogs were vaccinated intranasally with a single dose of the respective vaccines. The third group served as unvaccinated controls. All vaccinated dogs subsequently developed serum antibody titers to Bb that persisted for at least 1 year. Following Bb challenge 1 year after vaccination, all vaccinated dogs, regardless of group, showed significantly fewer clinical signs and shed significantly fewer challenge organisms than unvaccinated controls. These results demonstrate that intranasal administration of a single dose of monovalent attenuated Bb vaccine or trivalent vaccine containing attenuated Bb, CPI, and CAV-2 provides 1 year of protection against Bb.

  4. Quadrivalent meningococcal (MenACWY-TT) conjugate vaccine or a fourth dose of H. influenzae-N. meningitidis C/Y conjugate vaccine (HibMenCY-TT) is immunogenic in toddlers who previously received three doses of HibMenCY-TT in infancy.

    Science.gov (United States)

    Leonardi, Michael; Latiolais, Thomas; Sarpong, Kwabena; Simon, Michael; Twiggs, Jerry; Lei, Paul; Rinderknecht, Stephen; Blatter, Mark; Bianco, Veronique; Baine, Yaela; Friedland, Leonard R; Miller, Jacqueline M

    2015-02-11

    Immunogenicity and safety of a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT were evaluated in the second year of life in HibMenCY-TT-primed toddlers. Healthy infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine; or Hib-TT and DTaP-HBV-IPV (control). Recipients of HibMenCY-TT+DTaP-HBV-IPV were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months; MenACWY-TT co-administered with DTaP at 15-18 months; or HibMenCY-TT at 12-15 months and DTaP at 15-18 months. Controls received DTaP only at 15-18 months due to Hib conjugate vaccine shortage. Serum bactericidal activity using human complement (hSBA) and safety were assessed one month after meningococcal vaccination. After vaccination with MenACWY-TT at 12-15 months or MenACWY-TT+DTaP at 15-18 months, all subjects previously primed for serogroups C/Y had hSBA ≥1:8 for these serogroups. At least 96.1% also had hSBA ≥1:8 for serogroups A/W. All subjects in the HibMenCY-TT group had hSBA ≥1:8 for serogroups C/Y. All pre-defined statistical criteria for meningococcal immunogenicity were satisfied. All vaccination regimens had acceptable safety profiles. Children primed with three doses of HibMenCY-TT who then received a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT had robust increases in hSBA titers for serogroups C/Y. These data provide support that MenACWY-TT, given with or without the fourth scheduled dose of DTaP could be administered as an alternative to a fourth dose of HibMenCY-TT in the second year of life. This study (110870/110871) is registered at www.clinicaltrials.gov NCT00614614. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Immunogenicity of a 2-dose priming and booster vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine

    DEFF Research Database (Denmark)

    Silfverdal, Sven Arne; Høgh, Birthe; Bergsaker, Marianne Riise

    2009-01-01

    BACKGROUND: The immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was determined following a simplified 2-dose priming and the more commonly employed 3-dose priming both followed by a booster dose. METHODS: A total of 351 healthy....... RESULTS: Depending on the serotype, the percentages of subjects reaching the ELISA antibody threshold of 0.2 microg/mL were 92.8% to 98.0% following 2 primary doses and 96.1% to 100% following 3 primary doses except for serotype 6B (55.7% and 63.1%, respectively) and serotype 23F (69.3% and 77...

  6. Immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine in infants: a comparative, observer-blind, randomised, controlled trial.

    Science.gov (United States)

    Sáez-Llorens, Xavier; Clemens, Ralf; Leroux-Roels, Geert; Jimeno, José; Clemens, Sue Ann Costa; Weldon, William C; Oberste, M Steven; Molina, Natanael; Bandyopadhyay, Ananda S

    2016-03-01

    Following the proposed worldwide switch from trivalent oral poliovirus vaccine (tOPV) to bivalent types 1 and 3 OPV (bOPV) in 2016, inactivated poliovirus vaccine (IPV) will be the only source of protection against poliovirus type 2. With most countries opting for one dose of IPV in routine immunisation schedules during this transition because of cost and manufacturing constraints, optimisation of protection against all poliovirus types will be a priority of the global eradication programme. We assessed the immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine (mIPV2HD) in infants. This observer-blind, comparative, randomised controlled trial was done in a single centre in Panama. We enrolled healthy infants who had not received any previous vaccination against poliovirus. Infants were randomly assigned (1:1) by computer-generated randomisation sequence to receive a single dose of either mIPV2HD or standard trivalent IPV given concurrently with a third dose of bOPV at 14 weeks of age. At 18 weeks, all infants were challenged with one dose of monovalent type 2 OPV (mOPV2). Primary endpoints were seroconversion and median antibody titres to type 2 poliovirus 4 weeks after vaccination with mIPV2HD or IPV; and safety (as determined by the proportion and nature of serious adverse events and important medical events for 8 weeks after vaccination). The primary immunogenicity analyses included all participants for whom a post-vaccination blood sample was available. All randomised participants were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02111135. Between April 14 and May 9, 2014, 233 children were enrolled and randomly assigned to receive mIPV2HD (117 infants) or IPV (116 infants). 4 weeks after vaccination with mIPV2HD or IPV, seroconversion to poliovirus type 2 was recorded in 107 (93·0%, 95% CI 86·8-96·9) of 115 infants in the mIPV2HD group compared with 86 (74·8%, 65·8

  7. Estimating skin sensitization potency from a single dose LLNA.

    Science.gov (United States)

    Roberts, David W

    2015-04-01

    Skin sensitization is an important aspect of safety assessment. The mouse local lymph node assay (LLNA) developed in the 1990 s is an in vivo test used for skin sensitization hazard identification and characterization. More recently a reduced version of the LLNA (rLLNA) has been developed as a means of identifying, but not quantifying, sensitization hazard. The work presented here is aimed at enabling rLLNA data to be used to give quantitative potency information that can be used, inter alia, in modeling and read-across approaches to non-animal based potency estimation. A probit function has been derived enabling estimation of EC3 from a single dose. This has led to development of a modified version of the rLLNA, whereby as a general principle the SI value at 10%, or at a lower concentration if 10% is not testable, is used to calculate the EC3. This version of the rLLNA has been evaluated against a selection of chemicals for which full LLNA data are available, and has been shown to give EC3 values in good agreement with those derived from the full LLNA. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Serial Myocardial Imaging after a Single Dose of Thallium-201

    Directory of Open Access Journals (Sweden)

    Takahiko Kamata

    2014-10-01

    Full Text Available Although thallium-201 exercise scintigraphy has been established for the detection of myocardial ischemia and viability, little is known regarding the myocardial thallium-201 kinetics during angioplasty. Herein, we report a 77-year old man with angina pectoris, in whom serial myocardial imaging after a single dose of thallium-201 was helpful in identifying not only the culprit lesion and myocardial viability, but also the dynamic changes in myocardial perfusion during angioplasty. Thallium-201 images after exercise showed a perfusion defect in the inferior wall, with a trivial redistribution 3 hours after the exercise and a marked improvement 24 hours later. Coronary angiography, performed 27 hours after exercise scintigraphy, showed severe stenosis in the right coronary artery. Guidewire crossing of the lesion interrupted the antegrade flow, which was restored after balloon dilation and stent implantation. Thallium-201 images, 2 hours after angioplasty (i.e., 30 hours after exercise, showed a decreased tracer uptake in the inferior wall, which improved the next day (i.e., 48 hours after exercise. Cardiac biomarkers were negative in the clinical course.

  9. The D1 method: career dose estimation from a combination of historical monitoring data and a single year's dose data

    International Nuclear Information System (INIS)

    Sont, W.N.

    1995-01-01

    A method is introduced to estimate career doses from a combination of historical monitoring data and a single year's dose data. This method, called D1 eliminates the bias arising from incorporating historical dose data from times when occupational doses were generally much higher than they are today. Doses calculated by this method are still conditional on the preservation of the status quo in the effectiveness of radiation protection. The method takes into account the variation of the annual dose, and of the probability of being monitored, with the time elapsed since the start of a career. It also allows for the calculation of a standard error of the projected career dose. Results from recent Canadian dose data are presented. (author)

  10. [VACCINES].

    Science.gov (United States)

    Bellver Capella, Vincente

    2015-10-01

    Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.

  11. Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults >= 60 years of age

    NARCIS (Netherlands)

    Vermeulen, Joost N.; Lange, Joep M. A.; Tyring, Stephen K.; Peters, Patrick H.; Nunez, Margaret; Poland, Gregory; Levin, Myron J.; Freeman, Carrie; Chalikonda, Ira; Li, Jianjun; Smith, Jeffrey G.; Caulfield, Michael J.; Stek, Jon E.; Chan, Ivan S. F.; Vessey, Rupert; Schödel, Florian P.; Annunziato, Paula W.; Schlienger, Katia; Silber, Jeffrey L.

    2012-01-01

    Background: Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a

  12. Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

    Science.gov (United States)

    Andrade, Roberto; Rodriguez-Barradas, Maria C; Yasukawa, Kosuke; Villarreal, Erick; Ross, Michael; Serpa, Jose A

    2017-03-15

    Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients. We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period. Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results. When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis. NCT02611765. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  13. Thimerosal in Flu Vaccine

    Science.gov (United States)

    ... Seasonal Avian Swine Variant Pandemic Other Thimerosal in Flu Vaccine Questions & Answers Language: English (US) Español Recommend ... and/or fungi from contaminating the vaccine. Do flu vaccines contain thimerosal? Flu vaccines in multi-dose ...

  14. Anti-HBs in immunized children with cuban hepatitis B vaccine and impact of booster dose after five years

    International Nuclear Information System (INIS)

    Dahifar, H.; Mousavi, F.; Ghorbani, A.

    2008-01-01

    Hepatitis B virus infection and associated diseases are a major public health problem. This study was planned to find out the persistence of antibody against hepatitis B surface antigen in Iranian vaccinated children after five years. Anti-HBs titers in a group of healthy good - responder children who were vaccinated with Cuban hepatitis B vaccine in infancy were measured after five years. Children with antibody titers <100 mlU/ml were revaccinated and retested after four weeks. Mean anti-HBs titers in 68 children (29 females, 39 males) were 482.1 mlU/ml at six months after the third dose of primary vaccination and 153 mlU/ml at five years later. Total mean anti-HBs titers in 36 (52.9%) children out of 68 (17 females, 19 males) were 38.3 mlU/ml and 4(5.8%) of 68 children (two of each sexes) had no detectable antibody after five years. Total mean anti-HBs titers in these hypo- responder and non- responder were 774.3 mlU/ml and 625.5 mlU/ml respectively after booster dose. In a group of children, who were immunized with Cuban hepatitis B vaccine from birth, anti-HBS titers fell at 6.5 years of age and almost half of children became hypo responder or no responder and their anti-HBs titers developed secondary rise after booster vaccination. All children showed immunologic memory to a booster dose. (author)

  15. Analysis of the dose-sparing effect of adjuvanted Sabin-inactivated poliovirus vaccine (sIPV).

    Science.gov (United States)

    Li, Zhuofan; Ding, Wenting; Guo, Qi; Liu, Ze; Zhu, Zhe; Song, Shaohui; Li, Weidong; Liao, Guoyang

    2018-03-30

    Sabin-based inactivated poliovirus vaccine(sIPV) is gradually replacing live-attenuated oral polio vaccine(OPV). Sabin-inactivated poliovirus vaccine(sIPV) has played a vital role in reducing economic burden of poliomyelitis and maintaining appropriate antibody levels in the population. However, due to its high cost and limited manufacturing capacity, sIPV cannot reach its full potential for global poliovirus eradication in developing countries. Therefore, to address this situation, we designed this study to evaluate the dose-sparing effects of AS03, CpG oligodeoxynucleotides (CpG-ODN) and polyinosinic:polycytidylic acid (PolyI:C) admixed with sIPV in rats. Our results showed that a combination of 1/4-dose sIPV adjuvanted with AS03 or AS03 with BW006 provides a seroconversion rate similar to that of full-dose sIPV without adjuvant and that, this rate is 5-fold higher than that of 1/4-dose sIPV without adjuvant after the first immunization. The combination of AS03 or AS03 with BW006 as an adjuvant effectively reduced sIPV dose by at least 4-fold and induced both humoral and cellular immune responses. Therefore, our study revealed that the combination of AS03 or AS03 with BW006 is a promising adjuvant for sIPV development.

  16. Mumps outbreak in Israel's highly vaccinated society: are two doses enough?

    Science.gov (United States)

    Anis, E; Grotto, I; Moerman, L; Warshavsky, B; Slater, P E; Lev, B

    2012-03-01

    Mumps outbreaks in recent years have given rise to questions about the effectiveness of the mumps vaccine. This study examined the epidemiological data from a recent mumps outbreak in Israel and from outbreaks in other countries with high vaccination coverage, and considered whether long-established vaccination policies designed to protect against mumps are in need of revision. Of over 5000 case patients in the Israeli outbreak, half of whom were in the Jerusalem health district, nearly 40% were aged ≥15 years and, of those whose vaccination status was known, 78% had been fully vaccinated for their age - features similar to those in recent mumps outbreaks in Europe and North America. The epidemiological and laboratory evidence suggests that many previously vaccinated adolescents and young adults are now susceptible to mumps because their vaccine-based immunity has waned. Booster vaccination programmes for those at high risk of infection during mumps outbreaks - particularly those in congregate living environments - merit priority consideration.

  17. Protein carriers of conjugate vaccines

    Science.gov (United States)

    Pichichero, Michael E

    2013-01-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

  18. Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis

    Science.gov (United States)

    Suputtamongkol, Yupin; Premasathian, Nalinee; Bhumimuang, Kid; Waywa, Duangdao; Nilganuwong, Surasak; Karuphong, Ekkapun; Anekthananon, Thanomsak; Wanachiwanawin, Darawan; Silpasakorn, Saowaluk

    2011-01-01

    Background Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined. Methods A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up. Results Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2–76) weeks in albendazole group, 39 (2–74) weeks in single dose ivermectin group, and 26 (2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin

  19. Long-Term Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue Vaccine and Evaluation of a Booster Dose Administered to Healthy Thai Children.

    Science.gov (United States)

    Watanaveeradej, Veerachai; Simasathien, Sriluck; Mammen, Mammen P; Nisalak, Ananda; Tournay, Elodie; Kerdpanich, Phirangkul; Samakoses, Rudiwilai; Putnak, Robert J; Gibbons, Robert V; Yoon, In-Kyu; Jarman, Richard G; De La Barrera, Rafael; Moris, Philippe; Eckels, Kenneth H; Thomas, Stephen J; Innis, Bruce L

    2016-06-01

    We evaluated the safety and immunogenicity of two doses of a live-attenuated, tetravalent dengue virus vaccine (F17/Pre formulation) and a booster dose in a dengue endemic setting in two studies. Seven children (7- to 8-year-olds) were followed for 1 year after dose 2 and then given a booster dose (F17/Pre formulation), and followed for four more years (Child study). In the Infant study, 49 2-year-olds, vaccinated as infants, were followed for approximately 3.5 years after dose 2 and then given a booster dose (F17) and followed for one additional year. Two clinically notable events were observed, both in dengue vaccine recipients in the Infant study: 1 case of dengue approximately 2.7 years after dose 2 and 1 case of suspected dengue after booster vaccinations. The booster vaccinations had a favorable safety profile in terms of reactogenicity and adverse events reported during the 1-month follow-up periods. No vaccine-related serious adverse events were reported during the studies. Neutralizing antibodies against dengue viruses 1-4 waned during the 1-3 years before boosting, which elicited a short-lived booster response but did not provide a long-lived, multivalent antibody response in most subjects. Overall, this candidate vaccine did not elicit a durable humoral immune response. © The American Society of Tropical Medicine and Hygiene.

  20. Economic and clinical evaluation of a catch-up dose of 13-valent pneumococcal conjugate vaccine in children already immunized with three doses of the 7-valent vaccine in Italy.

    Science.gov (United States)

    Boccalini, Sara; Azzari, Chiara; Resti, Massimo; Valleriani, Claudia; Cortimiglia, Martina; Tiscione, Emilia; Bechini, Angela; Bonanni, Paolo

    2011-11-28

    A new 13-valent conjugated polysaccharide vaccine (PCV13) against Streptococcus pneumoniae infections, which replaced the 7-valent vaccine (PCV7) in the regional immunization programmes for newborns and children who started but not completed the 3 doses schedule of PCV7, is available in Italy since 2010. The opportunity of administering a further dose of PCV13 to children under 5 years of age who had already completed their vaccination with PCV7, with the aim of extending the serotype coverage, triggered an animated scientific debate. The purpose of this study was to perform a clinical/economic evaluation of the administration of a dose of PCV13, in a catch-up programme, for children under 5 years of age, who had already received 3 doses of PCV7. A mathematical model of the clinical/economic impact of the adoption of 4 catch-up strategies with PCV13 (children up to 24, 36, 48 and 60 months old) was set up, with a vaccination coverage of 80%, versus immunization with 3 doses of PCV7 without the catch-up programme. The time span covered by the simulation was 5.5 years. The following clinical outcomes of infection were evaluated: hospitalised meningitis/sepsis, hospitalised bacteraemic pneumonias (complicated and uncomplicated), hospitalised non-bacteraemic pneumonias, and non-hospitalised pneumonias. The administration of one dose of PCV13 to children up to 60 months of age significantly reduces the number of cases of pneumococcal diseases (especially, non-hospitalised pneumonias, 80% of all events prevented, and hospitalised cases of non-bacteraemic pneumococcal pneumonias, 15% of all events prevented) and, subsequently, the relative cost for medical treatment. This results in savings for medical costs amounting to more than 1,000,000 Euros when vaccinating children under 24 months of age (up to almost 3 million Euros for children up to 60 months). More than half of those savings are attributable to avoided hospitalised cases of non-bacteraemic pneumococcal

  1. Latent Membrane Protein 1 as a molecular adjuvant for single-cycle lentiviral vaccines

    Directory of Open Access Journals (Sweden)

    Rahmberg Andrew R

    2011-05-01

    Full Text Available Abstract Background Molecular adjuvants are a promising method to enhance virus-specific immune responses and protect against HIV-1 infection. Immune activation by ligands for receptors such as CD40 can induce dendritic cell activation and maturation. Here we explore the incorporation of two CD40 mimics, Epstein Barr Virus gene LMP1 or an LMP1-CD40 chimera, into a strain of SIV that was engineered to be limited to a single cycle of infection. Results Full length LMP1 or the chimeric protein LMP1-CD40 was cloned into the nef-locus of single-cycle SIV. Human and Macaque monocyte derived macrophages and DC were infected with these viruses. Infected cells were analyzed for activation surface markers by flow cytometry. Cells were also analyzed for secretion of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12p70 and TNF by cytometric bead array. Conclusions Overall, single-cycle SIV expressing LMP1 and LMP1-CD40 produced a broad and potent TH1-biased immune response in human as well as rhesus macaque macrophages and DC when compared with control virus. Single-cycle SIV-LMP1 also enhanced antigen presentation by lentiviral vector vaccines, suggesting that LMP1-mediated immune activation may enhance lentiviral vector vaccines against HIV-1.

  2. Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Bonde, J; Rasmussen, S N

    1992-01-01

    Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr r...

  3. An update of cost-effectiveness of rotavirus vaccination in indonesia: Takinga birth-dose vaccination strategy into account

    NARCIS (Netherlands)

    Suwantika, A.A.; Setiawan, D.; Atthobari, J.; Postma, M.J.

    2014-01-01

    Objectives: Rotavirus infection was reported as the major cause of severe diarrhea in children under 5-years-old in Indonesia. A low cost rotavirus vaccine to protect infants from birth has been developed for developing countries, such as Indonesia. This study aims to update our initial analysis on

  4. Delayed Dosing of Oral Rotavirus Vaccine Demonstrates Decreased Risk of Rotavirus Gastroenteritis Associated With Serum Zinc: A Randomized Controlled Trial.

    Science.gov (United States)

    Colgate, E Ross; Haque, Rashidul; Dickson, Dorothy M; Carmolli, Marya P; Mychaleckyj, Josyf C; Nayak, Uma; Qadri, Firdausi; Alam, Masud; Walsh, Mary Claire; Diehl, Sean A; Zaman, K; Petri, William A; Kirkpatrick, Beth D

    2016-09-01

    Rotavirus is the world's leading cause of childhood diarrheal death. Despite successes, oral rotavirus vaccines are less effective in developing countries. In an urban slum of Dhaka, we performed active diarrhea surveillance to evaluate monovalent G1P[8] rotavirus vaccine (RV1) efficacy and understand variables contributing to risk of rotavirus diarrhea (RVD). We performed a randomized controlled trial of monovalent oral rotavirus vaccine (RV1). Seven hundred healthy infants received RV1 or no RV1 (1:1) using delayed dosing (10 and 17 weeks) and were followed for 1 year. Intensive diarrhea surveillance was performed. The primary outcome was ≥1 episode of RVD. Nutritional, socioeconomic, and immunologic factors were assessed by logistic regression best-subsets analysis for association with risk of RVD and interactions with vaccine arm. Incidence of all RVD was 38.3 cases per 100 person-years. Per-protocol RV1 efficacy was 73.5% (95% confidence interval [CI], 45.8%-87.0%) against severe RVD and 51% (95% CI, 33.8%-63.7%) against all RVD. Serum zinc level (odds ratio [OR], 0.77; P = .002) and lack of rotavirus immunoglobulin A (IgA) seroconversion (OR, 1.95; P = .018) were associated with risk of RVD, independent of vaccination status. Water treatment and exclusive breastfeeding were of borderline significance. Factors not associated with RVD included height for age at 10 weeks, vitamin D, retinol binding protein, maternal education, household income, and sex. In an urban slum with high incidence of RVD, the efficacy of RV1 against severe RVD was higher than anticipated in the setting of delayed dosing. Lower serum zinc level and lack of IgA seroconversion were associated with increased risk of RVD independent of vaccination. NCT01375647. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  5. Risk of Injection-Site Abscess among Infants Receiving a Preservative-Free, Two-Dose Vial Formulation of Pneumococcal Conjugate Vaccine in Kenya

    Science.gov (United States)

    Burton, Deron C.; Bigogo, Godfrey M.; Audi, Allan O.; Williamson, John; Munge, Kenneth; Wafula, Jackline; Ouma, Dominic; Khagayi, Sammy; Mugoya, Isaac; Mburu, James; Muema, Shadrack; Bauni, Evasius; Bwanaali, Tahreni; Feikin, Daniel R.; Ochieng, Peter M.; Mogeni, Ondari D.; Otieno, George A.; Olack, Beatrice; Kamau, Tatu; Van Dyke, Melissa K.; Chen, Robert; Farrington, Paddy; Montgomery, Joel M.; Breiman, Robert F.; Scott, J. Anthony G.; Laserson, Kayla F.

    2015-01-01

    There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10). We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants) were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance) and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance). Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator). A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose). The risk ratio for abscess following injection with the second (41 per 100,000) vs first (33 per 100,000) vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37–4.06). The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12–8.56) and 0.27 (95% CI 0.14–0.54) when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study. PMID:26509274

  6. Control of hypertension with single daily doses of sotalol hydrochloride.

    Science.gov (United States)

    Gabriel, R

    A study was carried out in 12 previously untreated hypertensive patients to assess the efficacy of sotalol given in a once-daily dosage regimen. After an initial dosage titration period (mean 3 weeks) during which diastolic pressure was stabilized at less than 100 mmHg, all patients were satisfactorily maintained on a constant once-daily dose of sotalol for 3 months. Eight of the 12 patients required 320 mg or less daily (mean dose 190 mg). Whilst blood pressure remained controlled for at least 26 hours after daily doses the pulse rate, counted at the same time, showed escape from beta-blockade. Side-effects (vivid dreams) were reported in only 1 patient.

  7. Intranasal administration of a therapeutic HIV vaccine (Vacc-4x induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Kristin Brekke

    Full Text Available Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant.Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β.Vacc-4x proliferative T cell responses increased only among the vaccinated (p ≤ 0.031. The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037 and developed larger DTH (p = 0.005 than the adjuvant group. Rectal (distal Vacc-4x IgA and IgG antibodies also increased (p = 0.043 in this group. In contrast, the high dose generated higher nasal (local Vacc-4x IgA (p = 0.028 and serum IgG (p = 0.030 antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = -0.82, p < 0.001 and high regulation (r = 0.61, p = 0.010 at baseline.Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation.ClinicalTrials.gov NCT01473810.

  8. Analyzed immunogenicity of fractional doses of Sabin-inactivated poliovirus vaccine (sIPV) with intradermal delivery in rats.

    Science.gov (United States)

    Ma, Lei; Cai, Wei; Sun, Mingbo; Cun, Yina; Zhou, Jian; Liu, Jing; Hu, Wenzhu; Zhang, Xinwen; Song, Shaohui; Jiang, Shude; Liao, Guoyang

    2016-12-01

    The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one-third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90 th days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions

  9. Vaccines for preventing typhoid fever.

    Science.gov (United States)

    Milligan, Rachael; Paul, Mical; Richardson, Marty; Neuberger, Ami

    2018-05-31

    )A three-dose schedule of Ty21a vaccine probably prevents around half of typhoid cases during the first three years after vaccination (cumulative efficacy 2.5 to 3 years: 50%, 95% CI 35% to 61%, 4 trials, 235,239 participants, moderate-certainty evidence). These data include patients aged 3 to 44 years.Compared with placebo, this vaccine probably does not cause more vomiting, diarrhoea, nausea or abdominal pain (2 trials, 2066 participants; moderate-certainty evidence), headache, or rash (1 trial, 1190 participants; moderate-certainty evidence); however, fever (2 trials, 2066 participants; moderate-certainty evidence) is probably more common following vaccination.Vi polysaccharide vaccine (injection, one dose)A single dose of Vi polysaccharide vaccine prevents around two-thirds of typhoid cases in the first year after vaccination (year 1: 69%, 95% CI 63% to 74%; 3 trials, 99,979 participants; high-certainty evidence). In year 2, trial results were more variable, with the vaccine probably preventing between 45% and 69% of typhoid cases (year 2: 59%, 95% CI 45% to 69%; 4 trials, 194,969 participants; moderate-certainty evidence). These data included participants aged 2 to 55 years of age.The three-year cumulative efficacy of the vaccine may be around 55% (95% CI 30% to 70%; 11,384 participants, 1 trial; low-certainty evidence). These data came from a single trial conducted in South Africa in the 1980s in participants aged 5 to 15 years.Compared with placebo, this vaccine probably did not increase the incidence of fever (3 trials, 132,261 participants; moderate-certainty evidence) or erythema (3 trials, 132,261 participants; low-certainty evidence); however, swelling (3 trials, 1767 participants; moderate-certainty evidence) and pain at the injection site (1 trial, 667 participants; moderate-certainty evidence) were more common in the vaccine group.Vi-rEPA vaccine (two doses)Administration of two doses of the Vi-rEPA vaccine probably prevents between 50% and 96% of typhoid

  10. Effects of a Single Dose of Caffeine on Resting Cardiovascular ...

    African Journals Online (AJOL)

    The objective of this study was to determine the effect of 5mg/kg body weight dose of caffeine on cardiovascular system of normal young adult males of Black African Origin. Twenty normal young adult male volunteers participated. A repeated measures 2 randomized Crosse over (counter balanced) double blind design was ...

  11. The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial.

    Science.gov (United States)

    Huttner, Angela; Dayer, Julie-Anne; Yerly, Sabine; Combescure, Christophe; Auderset, Floriane; Desmeules, Jules; Eickmann, Markus; Finckh, Axel; Goncalves, Ana Rita; Hooper, Jay W; Kaya, Gürkan; Krähling, Verena; Kwilas, Steve; Lemaître, Barbara; Matthey, Alain; Silvera, Peter; Becker, Stephan; Fast, Patricia E; Moorthy, Vasee; Kieny, Marie Paule; Kaiser, Laurent; Siegrist, Claire-Anne

    2015-10-01

    Safe and effective vaccines against Ebola could prevent or control outbreaks. The safe use of replication-competent vaccines requires a careful dose-selection process. We report the first safety and immunogenicity results in volunteers receiving 3 × 10(5) plaque-forming units (pfu) of the recombinant vesicular stomatitis virus-based candidate vaccine expressing the Zaire Ebola virus glycoprotein (rVSV-ZEBOV; low-dose vaccinees) compared with 59 volunteers who had received 1 ×10(7) pfu (n=35) or 5 × 10(7) pfu (n=16) of rVSV-ZEBOV (high-dose vaccinees) or placebo (n=8) before a safety-driven study hold. The Geneva rVSV-ZEBOV study, an investigator-initiated phase 1/2, dose-finding, placebo-controlled, double-blind trial conducted at the University Hospitals of Geneva, Switzerland, enrolled non-pregnant, immunocompetent, and otherwise healthy adults aged 18-65 years. Participants from the low-dose group with no plans to deploy to Ebola-aff5cted regions (non-deployable) were randomised 9:1 in a double-blind fashion using randomly permuted blocks of varying sizes to a single injection of 3 × 10(5) pfu or placebo, whereas deployable participants received single-injection 3 × 10(5) pfu open-label. Primary safety and immunogenicity outcomes were the incidence of adverse events within 14 days of vaccination and day-28 antibody titres, respectively, analysed by intention to treat. After viral oligoarthritis was observed in 11 of the first 51 vaccinees (22%) receiving 10(7) or 5 × 10(7) pfu, 56 participants were given a lower dose (3 × 10(5) pfu, n=51) or placebo (n=5) to assess the effect of dose reduction on safety and immunogenicity. This trial is ongoing with a follow-up period of 12 months; all reported results are from interim databases. This study is registered with ClinicalTrials.gov, number NCT02287480. Between Jan 5 and Jan 26, 2015, 43 non-deployable participants received low-dose rVSV-ZEBOV (3 × 10(5) pfu) or placebo in a

  12. Cost-effectiveness of hepatitis A vaccination in Indonesia

    Science.gov (United States)

    Suwantika, Auliya A; Beutels, Philippe; Postma, Maarten J

    2014-01-01

    Objective This study aims to assess the cost-effectiveness of hepatitis A immunization in Indonesia, including an explicit comparison between one-dose and two-dose vaccines. Methods An age-structured cohort model based on a decision tree was developed for the 2012 Indonesia birth cohort. Using the model, we made a comparison on the use of two-dose and one-dose vaccines. The model involved a 70-year time horizon with 1-month cycles for children less than 2 years old and annually thereafter. Monte Carlo simulations were used to examine the economic acceptability and affordability of the hepatitis A vaccination. Results Vaccination would save US$ 3 795 148 and US$ 2 892 920 from the societal perspective, for the two-dose and one-dose vaccine schedules, respectively, in the context of hepatitis A treatment. It also would save 8917 and 6614 discounted quality-adjusted-life-years (QALYs), respectively. With the vaccine price of US$ 3.21 per dose, the implementation of single dose vaccine would yield an incremental cost-effectiveness ratio (ICER) of US$ 4933 per QALY gained versus no vaccination, whereas the two-dose versus one-dose schedule would cost US$ 14 568 per QALY gained. Considering the 2012 gross-domestic-product (GDP) per capita in Indonesia of US$ 3557, the results indicate that hepatitis A vaccination would be a cost-effective intervention, both for the two-dose and one-dose vaccine schedules in isolation, but two-dose vaccination would no longer be cost-effective if one-dose vaccination is a feasible option. Vaccination would be 100% affordable at budgets of US$ 71 408 000 and US$ 37 690 000 for the implementation of the two-dose and one-dose vaccine schedules, respectively. Conclusions The implementation of hepatitis A vaccination in Indonesia would be a cost-effective health intervention under the market vaccine price. Given the budget limitations, the use of a one-dose-vaccine schedule would be more realistic to be applied than a two-dose

  13. The Duration of Intestinal Immunity After an Inactivated Poliovirus Vaccine Booster Dose in Children Immunized With Oral Vaccine: A Randomized Controlled Trial.

    Science.gov (United States)

    John, Jacob; Giri, Sidhartha; Karthikeyan, Arun S; Lata, Dipti; Jeyapaul, Shalini; Rajan, Anand K; Kumar, Nirmal; Dhanapal, Pavithra; Venkatesan, Jayalakshmi; Mani, Mohanraj; Hanusha, Janardhanan; Raman, Uma; Moses, Prabhakar D; Abraham, Asha; Bahl, Sunil; Bandyopadhyay, Ananda S; Ahmad, Mohammad; Grassly, Nicholas C; Kang, Gagandeep

    2017-02-15

    In 2014, 2 studies showed that inactivated poliovirus vaccine (IPV) boosts intestinal immunity in children previously immunized with oral poliovirus vaccine (OPV). As a result, IPV was introduced in mass campaigns to help achieve polio eradication. We conducted an open-label, randomized, controlled trial to assess the duration of the boost in intestinal immunity following a dose of IPV given to OPV-immunized children. Nine hundred healthy children in Vellore, India, aged 1-4 years were randomized (1:1:1) to receive IPV at 5 months (arm A), at enrollment (arm B), or no vaccine (arm C). The primary outcome was poliovirus shedding in stool 7 days after bivalent OPV challenge at 11 months. For children in arms A, B, and C, 284 (94.7%), 297 (99.0%), and 296 (98.7%), respectively, were eligible for primary per-protocol analysis. Poliovirus shedding 7 days after challenge was less prevalent in arms A and B compared with C (24.6%, 25.6%, and 36.4%, respectively; risk ratio 0.68 [95% confidence interval: 0.53-0.87] for A versus C, and 0.70 [0.55-0.90] for B versus C). Protection against poliovirus remained elevated 6 and 11 months after an IPV boost, although at a lower level than reported at 1 month. CTRI/2014/09/004979. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. First-in-human safety and immunogenicity investigations of three adjuvanted reduced dose inactivated poliovirus vaccines (IPV-Al SSI) compared to full dose IPV Vaccine SSI when given as a booster vaccination to adolescents with a history of IPV vaccination at 3, 5, 12months and 5years of age.

    Science.gov (United States)

    Lindgren, Line M; Tingskov, Pernille N; Justesen, Annette H; Nedergaard, Bettina S; Olsen, Klaus J; Andreasen, Lars V; Kromann, Ingrid; Sørensen, Charlotte; Dietrich, Jes; Thierry-Carstensen, Birgit

    2017-01-23

    There is a demand of affordable IPV in the World. Statens Serum Institut (SSI) has developed three reduced dose IPV formulations adsorbed to aluminium hydroxide; 1/3 IPV-Al, 1/5 IPV-Al and 1/10 IPV-Al SSI, and now report the results of the first investigations in humans. 240 Danish adolescents, aged 10-15years, and childhood vaccinated with IPV were booster vaccinated with 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al or IPV Vaccine SSI. The booster effects (GMTRs) of the three IPV-Al SSI were compared to IPV Vaccine SSI, and evaluated for non-inferiority. The pre-vaccination GMTs were similar across the groups; 926 (type 1), 969 (type 2) and 846 (type 3) in the total trial population. The GMTRs by poliovirus type and IPV formulation were: Type 1: 17.0 (1/3 IPV-Al), 13.0 (1/5 IPV-Al), 7.1 (1/10 IPV-Al) and 42.2 (IPV Vaccine SSI). Type 2: 12.5 (1/3 IPV-Al), 13.1 (1/5 IPV-Al), 7.6 (1/10 IPV-Al) and 47.8 (IPV Vaccine SSI). Type 3: 14.5 (1/3 IPV-Al), 16.2 (1/5 IPV-Al), 8.9 (1/10 IPV-Al) and 62.4 (IPV Vaccine SSI) Thus, the three IPV-Al formulations were highly immunogenic, but inferior to IPV Vaccine SSI, in this booster vaccination trial. No SAE and no AE of severe intensity occurred. 59.2% of the subjects reported at least one AE. Injection site pain was the most frequent AE in all groups; from 24.6% to 43.3%. Injection site redness and swelling frequencies were<5% in most and<10% in all groups. The most frequent systemic AEs were fatigue (from 8.2% to 15.0%) and headache (from 15.0% to 28.3%). Most AEs were of mild intensity. In conclusion, the three IPV-Al SSI were safe in adolescents and the booster effects were satisfactory. ClinicalTrials.gov registration number: NCT02280447. Copyright © 2016. Published by Elsevier Ltd.

  15. Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults

    OpenAIRE

    Troy, Stephanie B.; Kouiavskaia, Diana; Siik, Julia; Kochba, Efrat; Beydoun, Hind; Mirochnitchenko, Olga; Levin, Yotam; Khardori, Nancy; Chumakov, Konstantin; Maldonado, Yvonne

    2015-01-01

    Background. Inactivated polio vaccine (IPV) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised populations. However, IPV is unaffordable for many developing countries. Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV, but prior studies, all using 20% of the standard dose used in intramuscular IPV, resulted in inferior antibody tit...

  16. Hypertrophic Cardiomyopathy After a Single Dose of Dexamethasone in a Preterm Infant

    Directory of Open Access Journals (Sweden)

    Yusuf Kale

    2015-08-01

    Full Text Available Dexamethasone is widely used in preterm infants with severe pulmonary disease. Hypertrophic cardiomyopathy (HCM is a transient side effect observed after multiple doses of dexamethasone. We report a preterm infant with myocardial hypertrophy after a single dose of dexamethasone (0.5 mg/kg used to treat laryngeal edema secondary to prolonged intubation. A benign course was observed without left ventricular outflow tract obstruction and with recovery within 4 weeks. Myocardial effects of dexamethasone may be independent of dose and duration of treatment. The risk/benefit ratio must be carefully considered before using even a single dose of dexamethasone in preterm infants.

  17. Determination of the minimum protective dose for bluetongue virus serotype 2 and 8 vaccines in sheep.

    Science.gov (United States)

    Modumo, Jacob; Venter, Estelle H

    2012-08-03

    Recent outbreaks of bluetongue virus (BTV) serotypes 2 and 8 in many European countries provided an opportunity to investigate the possibility of improving the safety of the modified live vaccines administered mainly in South Africa. Modified live vaccines (MLV) released at a titre of 5 x 104 PFU/mL, raised concerns and prompted the need to determine the minimum titre which will still be protective and also safe. The BTV serotypes 2 and 8 vaccines were produced at the following titres: 102 PFU/mL, 103 PFU/mL and 104 PFU/mL, and were injected into 24 sheep which were then monitored. Blood was collected on days 0, 3, 6, 9, 12, 15, 18, 21, 25, 28 and 4 months post vaccination, for seroconversion and viraemia studies. These sheep were later challenged at 4 months post vaccination using BTV infected cell culture material, they were then observed and bled and again tested for viraemia. There was no viraemia post vaccination, however, a febrile reaction did occur and seroconversion was demonstrated at low titres for both BTV 2 and 8. Although viraemia was demonstrated post challenge, sheep vaccinated with the low titre BTV 2 vaccine showed more than a 90% protection index at a lower titre of 103 PFU/mL, compared with BTV 8 that showed a protection index above 90% at all the titres used. It is recommended that for BTV 2 vaccine, sheep should be vaccinated at a titre of 103 PFU/mL and at a titre of 102 PFU/mL with BTV 8 vaccine.

  18. Determination of the minimum protective dose for bluetongue virus serotype 2 and 8 vaccines in sheep

    Directory of Open Access Journals (Sweden)

    Jacob Modumo

    2012-08-01

    Full Text Available Recent outbreaks of bluetongue virus (BTV serotypes 2 and 8 in many European countries provided an opportunity to investigate the possibility of improving the safety of the modified live vaccines administered mainly in South Africa. Modified live vaccines (MLV released at a titre of 5 x 104 PFU/mL, raised concerns and prompted the need to determine the minimum titre which will still be protective and also safe. The BTV serotypes 2 and 8 vaccines were produced at the following titres: 102 PFU/mL, 103 PFU/mL and 104 PFU/mL, and were injected into 24 sheep which were then monitored. Blood was collected on days 0, 3, 6, 9, 12, 15, 18, 21, 25, 28 and 4 months post vaccination, for seroconversion and viraemia studies. These sheep were later challenged at 4 months post vaccination using BTV infected cell culture material, they were then observed and bled and again tested for viraemia. There was no viraemia post vaccination, however, a febrile reaction did occur and seroconversion was demonstrated at low titres for both BTV 2 and 8. Although viraemia was demonstrated post challenge, sheep vaccinated with the low titre BTV 2 vaccine showed more than a 90% protection index at a lower titre of 103 PFU/mL, compared with BTV 8 that showed a protection index above 90% at all the titres used. It is recommended that for BTV 2 vaccine, sheep should be vaccinated at a titre of 103 PFU/mL and at a titre of 102 PFU/mL with BTV 8 vaccine.

  19. Immunogenicity and safety of low dose virosomal adjuvanted influenza vaccine administered intradermally compared to intramuscular full dose administration

    NARCIS (Netherlands)

    Künzi, Valérie; Klap, Jaco M.; Seiberling, Michael K.; Herzog, Christian; Hartmann, Katharina; Kürsteiner, Oliver; Kompier, Ronald; Grimaldi, Roberto; Goudsmit, Jaap

    2009-01-01

    BACKGROUND: Despite the established benefit of intramuscular (i.m.) influenza vaccination, new adjuvants and delivery methods for comparable or improved immunogenicity are being explored. Intradermal (i.d.) antigen administration is hypothesized to initiate an efficient immune response at reduced

  20. Effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: a randomized trial.

    Science.gov (United States)

    Wright, Jennifer G; Plikaytis, Brian D; Rose, Charles E; Parker, Scott D; Babcock, Janiine; Keitel, Wendy; El Sahly, Hana; Poland, Gregory A; Jacobson, Robert M; Keyserling, Harry L; Semenova, Vera A; Li, Han; Schiffer, Jarad; Dababneh, Hanan; Martin, Sandra K; Martin, Stacey W; Marano, Nina; Messonnier, Nancy E; Quinn, Conrad P

    2014-02-12

    We evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for anthrax vaccine adsorbed (AVA). AVA's originally licensed schedule was 6 subcutaneous (SQ) priming injections administered at months (m) 0, 0.5, 1, 6, 12 and 18 with annual boosters; a simpler schedule is desired. Through a multicenter randomized, double blind, non-inferiority Phase IV human clinical trial, the originally licensed schedule was compared to four alternative and two placebo schedules. 8-SQ group participants received 6 SQ injections with m30 and m42 "annual" boosters; participants in the 8-IM group received intramuscular (IM) injections according to the same schedule. Reduced schedule groups (7-IM, 5-IM, 4-IM) received IM injections at m0, m1, m6; at least one of the m0.5, m12, m18, m30 vaccine doses were replaced with saline. All reduced schedule groups received a m42 booster. Post-injection blood draws were taken two to four weeks following injection. Non-inferiority of the alternative schedules was compared to the 8-SQ group at m2, m7, and m43. Reactogenicity outcomes were proportions of injection site and systemic adverse events (AEs). The 8-IM group's m2 response was non-inferior to the 8-SQ group for the three primary endpoints of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer, and proportion of responders with a 4-fold rise in titer. At m7 anti-PA IgG GMCs for the three reduced dosage groups were non-inferior to the 8-SQ group GMCs. At m43, 8-IM, 5-IM, and 4-IM group GMCs were superior to the 8-SQ group. Solicited injection site AEs occurred at lower proportions in the IM group compared to SQ. Route of administration did not influence the occurrence of systemic AEs. A 3 dose IM priming schedule with doses administered at m0, m1, and m6 elicited long term immunological responses and robust immunological memory that was efficiently stimulated by a single booster vaccination at

  1. Safety and immunogenicity in man of a cell culture derived trivalent live attenuated seasonal influenza vaccine: a Phase I dose escalating study in healthy volunteers.

    Science.gov (United States)

    Heldens, Jacco; Hulskotte, Ellen; Voeten, Theo; Breedveld, Belinda; Verweij, Pierre; van Duijnhoven, Wilbert; Rudenko, Larissa; van Damme, Pierre; van den Bosch, Han

    2014-09-03

    Live attenuated influenza vaccine (LAIV) offers the promise of inducing a variety of immune responses thereby conferring protection to circulating field strains. LAIVs are based on cold adapted and temperature sensitive phenotypes of master donor viruses (MDVs) containing the surface glycoprotein genes of seasonal influenza strains. Two types of MDV lineages have been described, the Ann Arbor lineages and the A/Leningrad/17 and B/USSR/60 lineages. Here the safety and immunogenicity of a Madin Darby Canine Kidney - cell culture based, intranasal LAIV derived from A/Leningrad/17 and B/USSR, was evaluated in healthy influenza non-naive volunteers 18-50 years of age. In a double-blind, randomized, placebo-controlled design, single escalating doses of 1×10(5), 1×10(6), or 1×10(7) tissue culture infectious dose 50% (TCID50) of vaccine containing each of the three influenza virus re-assortants recommended by the World Health Organization for the 2008-2009 season were administered intranasally. A statistically significant geometric mean increase in hemagglutination inhibition titer was reached for influenza strain A/H3N2 after immunization with all doses of LAIV. For the A/H1N1 and B strains, the GMI in HI titer did not increase for any of the doses. Virus neutralization antibody titers showed a similar response pattern. A dose-response effect could not be demonstrated for any of the strains, neither for the HI antibody nor for the VN antibody responses. No influenza like symptoms, no nasal congestions, no rhinorrhea, or other influenza related upper respiratory tract symptoms were observed. In addition, no difference in the incidence or nature of adverse events was found between vaccine and placebo treated subjects. Overall, the results indicated that the LAIV for nasal administration is immunogenic (i.e. able to provoke an immune response) and safe both from the perspective of the attenuated virus and the MDCK cell line from which it was derived, and it warrants

  2. Management of urinary tract infections in pregnancy: a review with comments on single dose therapy.

    Science.gov (United States)

    Zinner, S H

    1992-01-01

    Most investigators agree that the adverse effects of urinary tract infections in pregnancy can be abrogated by effective early detection and treatment. However, the optimal methods for screening and treatment remain controversial. Although single-dose therapy has not been applied to pregnant women with acute pyelonephritis, most but not all studies which have compared single-dose with longer courses of beta-lactam or other antibiotics in pregnant asymptomatic bacteriuric women have shown no differences in outcome. This paper reviews recent trials of single-dose treatment of bacteriuria in pregnant women.

  3. Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity.

    Science.gov (United States)

    Mancebo, A; Casacó, A; González, B; Ledón, N; Sorlozabal, J; León, A; Gómez, D; González, Y; Bada, A M; González, C; Arteaga, M E; Ramírez, H; Fuentes, D

    2012-05-09

    CIMAvax-EGF consists of a human recombinant epidermal growth factor (EGF), coupled to P64k, a recombinant carrier protein from N. meningitis, and Montanide ISA 51 as adjuvant. The vaccine immunization induces a specific antibody production, inhibiting the EGF/EGF-R interaction through EGF deprivation. The objective of this study was to assess the CIMAvax-EGF toxicity in Sprague Dawley rats after intramuscular administration of repeated doses (6 months) and at the same time to determine if rat is a relevant species for studying CIMAvax-EGF vaccine. Rats were randomly distributed into four groups: control, Montanide ISA 51, treated with 1× and 15× of human total dose of the antigen. Animals were immunized weekly during 9 weeks, plus 9 immunizations every 14 days. Rats were inspected daily for clinical signs. Body weight, food consumption, and rectal temperature were measured during the administration of doses. Blood samples were collected for hematological, serum biochemical determinations and EGF titles at the beginning, three months and at the end of experimentation. Gross necropsy and histological examination of tissues were performed on animals at the end of the assay. Vaccine provoked the apparition of antibodies against EGF in the rats, demonstrating rat species relevance in these studies. Body weight gain, food and water consumption were not affected. CIMAvax-EGF and Montanide ISA 51 produced local damage at the administration site, showing multiple cysts and granulomas. Both vaccine-treated groups showed neutrophil elevation, besides an AST increase probably related to the damage at the administration site. Rectal temperature was found to be significantly higher in 15× treated group after immunizations, probably induced by the inflammatory process at the injection site. In summary, the clinical pathology findings together with the body temperature results, appear to be caused by the inflammatory reaction at the administration site of the vaccine, mainly

  4. Evaluation of a Booster Dose of Pentavalent Rotavirus Vaccine Co-Administered with Measles, Yellow Fever and Meningitis A Vaccines in 9-month-old Malian Infants.

    Science.gov (United States)

    Haidara, Fadima C; Tapia, Milagritos D; Sow, Samba O; Doumbia, Moussa; Coulibaly, Flanon; Diallo, Fatoumata; Traoré, Awa; Kodio, Mamoudou; Kelly, Corey L; Fitzpatrick, Meagan; Kotloff, Karen; Victor, John C; Neuzil, Kathleen

    2018-04-12

    Rotavirus vaccines given to infants are safe and efficacious. A booster dose of rotavirus vaccine could extend protection into the second year of life in low resource countries. We conducted an open-label, individual-randomized trial in Bamako, Mali. We assigned 600 9- to 11-month old infants to measles (MV), yellow fever (YFV), and meningococcal A conjugate vaccines with or without pentavalent rotavirus vaccine (PRV). We assessed non-inferiority of seroconversion and seroresponse rates (<10% difference) to MV, YFV and MenAV. We compared the seroresponse to PRV. Seroconversion to measles occurred in 255/261 (97.7%) and 246/252 (97.6%) of the PRV and control group; difference, 0.1% (95% CI, - 4.0 to 4.2). Seroresponse to YFV occurred in 48.1% (141/293) of the PRV group compared to 52.2% (153/293) of the control group; difference - 4.1% (95% CI, -12.2 to 4.0). A 4-fold rise in meningococcal A bactericidal titer was observed in 273/292 (93.5%) PRV recipients and 276/293 (94.2%) controls; difference, -0.7% (95% CI, - 5.2 to 3.8). Rises in anti-rotavirus IgA and IgG geometric mean concentrations were higher among PRV recipients (118 [95% CI, 91 to 154] and 364 [95% CI, 294 to 450]) compared to controls (68 [95% CI, 50 to 92] and 153 [95% CI, 114 to 207]. PRV did not interfere with MV and MenAV; this study could not rule out interference with YFV. PRV increased serum rotavirus antibody levels. NCT02286895.

  5. High-dose vitamin A supplementation administered with vaccinations after 6 months of age

    DEFF Research Database (Denmark)

    Fisker, Ane Bærent; Bale, Carlito; Jørgensen, Mathias Jul

    2013-01-01

    WHO recommends vitamin A supplementation (VAS) at vaccination contacts after six months of age. The effect of this recommendation on mortality has not been evaluated.......WHO recommends vitamin A supplementation (VAS) at vaccination contacts after six months of age. The effect of this recommendation on mortality has not been evaluated....

  6. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats

    NARCIS (Netherlands)

    Cornelissen, J.B.W.J.; Giessen, van der J.W.B.; Takumi, K.; Teunis, P.F.M.; Wisselink, H.J.

    2014-01-01

    High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment.

  7. Responses of Juvenile Black-tailed Prairie Dogs ( Cynomys ludovicianus ) to a Commercially Produced Oral Plague Vaccine Delivered at Two Doses.

    Science.gov (United States)

    Cárdenas-Canales, Elsa M; Wolfe, Lisa L; Tripp, Daniel W; Rocke, Tonie E; Abbott, Rachel C; Miller, Michael W

    2017-10-01

    We confirmed safety and immunogenicity of mass-produced vaccine baits carrying an experimental, commercial-source plague vaccine (RCN-F1/V307) expressing Yersinia pestis V and F1 antigens. Forty-five juvenile black-tailed prairie dogs ( Cynomys ludovicianus ) were randomly divided into three treatment groups (n=15 animals/group). Animals in the first group received one standard-dose vaccine bait (5×10 7 plaque-forming units [pfu]; STD). The second group received a lower-dose bait (1×10 7 pfu; LOW). In the third group, five animals received two standard-dose baits and 10 were left untreated but in contact. Two vaccine-treated and one untreated prairie dogs died during the study, but laboratory analyses ruled out vaccine involvement. Overall, 17 of 33 (52%; 95% confidence interval for binomial proportion [bCI] 34-69%) prairie dogs receiving vaccine-laden bait showed a positive anti-V antibody response on at least one sampling occasion after bait consumption, and eight (24%; bCI 11-42%) showed sustained antibody responses. The STD and LOW groups did not differ (P≥0.78) in their proportions of overall or sustained antibody responses after vaccine bait consumption. Serum from one of the nine (11%; bCI 0.3-48%) surviving untreated, in-contact prairie dogs also had detectable antibody on one sampling occasion. We did not observe any adverse effects related to oral vaccination.

  8. Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

    International Nuclear Information System (INIS)

    Storb, R.; Raff, R.F.; Graham, T.; Appelbaum, F.R.; Deeg, H.J.; Schuening, F.G.; Shulman, H.; Pepe, M.

    1993-01-01

    The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing 60 Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs

  9. Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults.

    OpenAIRE

    Anderson, E L; Bowers, T; Mink, C M; Kennedy, D J; Belshe, R B; Harakeh, H; Pais, L; Holder, P; Carlone, G M

    1994-01-01

    A meningococcal vaccine containing group A and C polysaccharides conjugated to CRM197 was evaluated in 50 adults. Vaccinees were entered into one of five groups: 30 adults received a single dose of either 22, 11, or 5.5 micrograms of the conjugated A-C vaccine; 10 received an approved meningococcal vaccine; and 10 received saline injections. Local and systemic reactions to vaccines were recorded, and immune responses were determined. The experimental meningococcal vaccine was well tolerated, ...

  10. 17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study.

    Science.gov (United States)

    Martins, Reinaldo M; Maia, Maria de Lourdes S; Farias, Roberto Henrique G; Camacho, Luiz Antonio B; Freire, Marcos S; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C; Lima, Sheila Maria B; Nogueira, Rita Maria R; Sá, Gloria Regina S; Hokama, Darcy A; de Carvalho, Ricardo; Freire, Ricardo Aguiar V; Pereira Filho, Edson; Leal, Maria da Luz Fernandes; Homma, Akira

    2013-04-01

    To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. INTERNATIONAL REGISTER: ISRCTN 38082350.

  11. A Dose-Response Relationship between Organic Mercury Exposure from Thimerosal-Containing Vaccines and Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    David A. Geier

    2014-09-01

    Full Text Available A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg exposure from thimerosal-containing (49.55% Hg by weight vaccines on the risk of neurodevelopmental disorders (NDs. Automated medical records were examined to identify cases and controls enrolled from their date-of-birth (1991–2000 in the Vaccine Safety Datalink (VSD project. ND cases were diagnosed with pervasive developmental disorder (PDD, specific developmental delay, tic disorder or hyperkinetic syndrome of childhood. In addition, putative non-thimerosal-related outcomes of febrile seizure, failure to thrive and cerebral degenerations were examined. The cumulative total dose of Hg exposure from thimerosal-containing hepatitis B vaccine (T-HBV administered within the first six months of life was calculated. On a per microgram of organic-Hg basis, PDD (odds ratio (OR = 1.054, specific developmental delay (OR = 1.035, tic disorder (OR = 1.034 and hyperkinetic syndrome of childhood (OR = 1.05 cases were significantly more likely than controls to receive increased organic-Hg exposure. By contrast, none of the non-thimerosal related outcomes were significantly more likely than the controls to have received increased organic-Hg exposure. Routine childhood vaccination may be an important public health tool to reduce infectious disease-associated morbidity/mortality, but the present study significantly associates organic-Hg exposure from T-HBV with an increased risk of an ND diagnosis.

  12. How much does it cost to get a dose of vaccine to the service delivery location? Empirical evidence from Vietnam's Expanded Program on Immunization.

    Science.gov (United States)

    Mvundura, Mercy; Kien, Vu Duy; Nga, Nguyen Tuyet; Robertson, Joanie; Cuong, Nguyen Van; Tung, Ho Thanh; Hong, Duong Thi; Levin, Carol

    2014-02-07

    Few studies document the costs of operating vaccine supply chains, but decision-makers need this information to inform cost projections for investments to accommodate new vaccine introduction. This paper presents empirical estimates of vaccine supply chain costs for Vietnam's Expanded Program on Immunization (EPI) for routine vaccines at each level of the supply chain, before and after the introduction of the pentavalent vaccine. We used micro-costing methods to collect resource-use data associated with storage and transportation of vaccines and immunization supplies at the national store, the four regional stores, and a sample of provinces, districts, and commune health centers. We collected stock ledger data on the total number of doses of vaccines handled by each facility during the assessment year. Total supply chain costs were estimated at approximately US$65,000 at the national store and an average of US$39,000 per region, US$5800 per province, US$2200 per district, and US$300 per commune health center. Across all levels, cold chain equipment capital costs and labor were the largest drivers of costs. The cost per dose delivered was estimated at US$0.19 before the introduction of pentavalent and US$0.24 cents after introduction. At commune health centers, supply chain costs were 104% of the value of vaccines before introduction of pentavalent vaccine and 24% after introduction, mainly due to the higher price per dose of the pentavalent vaccine. The aggregated costs at the last tier of the health system can be substantial because of the large number of facilities. Even in countries with high-functioning systems, empirical evidence on current costs from all levels of the system can help estimate resource requirements for expanding and strengthening resources to meet future immunization program needs. Other low- and middle-income countries can benefit from similar studies, in view of new vaccine introductions that will put strains on existing systems. Copyright

  13. A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly.

    Science.gov (United States)

    Levin, Yotam; Kochba, Efrat; Shukarev, Georgi; Rusch, Sarah; Herrera-Taracena, Guillermo; van Damme, Pierre

    2016-10-17

    Influenza remains a significant problem in elderly despite widespread vaccination coverage. This randomized, phase-I study in elderly compared different strategies of improving vaccine immunogenicity. A total of 370 healthy participants (⩾65years) were randomized equally 1:1:1:1:1:1 to six influenza vaccine treatments (approximately 60-63 participants per treatment arm) at day 1 that consisted of three investigational virosomal vaccine formulations at doses of 7.5, 15, and 45μg HA antigen/strain administered intradermally (ID) by MicronJet600™ microneedle device (NanoPass Technologies) or intramuscularly (IM), and three comparator registered seasonal vaccines; Inflexal V™ (Janssen) and MF59 adjuvanted Fluad™ (Novartis) administered IM and Intanza™ (Sanofi Pasteur) administered ID via Soluvia™ prefilled microinjection system (BD). Serological evaluations were performed at days 22 and 90 and safety followed-up for 6months. Intradermal delivery of virosomal vaccine using MicronJet600™ resulted in significantly higher immunogenicity than the equivalent dose of virosomal Inflexal V™ administered intramuscularly across most of the parameters and strains, as well as in some of the readouts and strains as compared with the 45μg dose of virosomal vaccine formulation. Of 370 participants, 300 (81.1%) reported ⩾1 adverse event (AE); more participants reported solicited local AEs (72.2%) than solicited systemic AEs (12.2%). Intradermal delivery significantly improved influenza vaccine immunogenicity compared with intramuscular delivery. Triple dose (45μg) virosomal vaccine did not demonstrate any benefit on vaccine's immunogenicity over 15μg commercial presentation. All treatments were generally safe and well-tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Evaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers.

    Science.gov (United States)

    Bai, Stephen A; Xiang, Qinfang; Finn, Andrew

    2016-02-01

    Buprenorphine, a partial μ-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. Both studies enrolled healthy volunteers, aged 18 to 55 years, who received concurrent oral naltrexone to reduce adverse events (AEs); subjects with a history or evidence of substance abuse or current use of any product affecting cytochrome P450 3A4 activity were excluded. The first study (n = 25) was a 5-period crossover trial with 4 single doses (75 and 300 and 300 and 1200 μg) of 2 formulations (F14 and F24) of buccal buprenorphine (BBUP) and a 300-μg intravenous dose of buprenorphine with a 7-day washout between periods. In the second study, each subject (n = 10) received 6 doses of 4 BBUP strengths (60, 120, 180, and 240 μg BID) in a dose-escalation design. Plasma concentrations of buprenorphine and norbuprenorphine were assayed, and pharmacokinetics were summarized with descriptive statistics and analyzed by using a linear mixed effects model (single-dose study). AEs were recorded. In the single-dose study, the 2 formulations exhibited comparable bioavailability of 46% to 51% that was independent of dose, with a single buprenorphine peak concentration from each BBUP dose occurring at 2.5 to 3 hours. The mean buprenorphine Cmax across the doses ranged from 0.17 ng/mL for the 75-µg dose to 1.43 ng/mL for the 1200-µg dose. AUC0-∞, AUC0-last, and Cmax were proportional to the dose of BBUP administered. Cmax of norbuprenorphine after BBUP administration was approximately one tenth that of buprenorphine Cmax. In the multiple-dose study, steady state was reached within 3 days of BID dosing. There was a linear increase in exposure across the dose range from 60 to 240 μg BID. Treatment-emergent AEs in both studies were consistent with those reported with opiate administration to

  15. Effect of single lithium doses on haemopoiesis regeneration after radiation exposure in mice

    International Nuclear Information System (INIS)

    Krajewski, K.

    1988-01-01

    The reported experiment failed to demonstrate any effect of single doses of lithium carbonate on haemopoiesis regeneration in experimental haematological syndrome of acute radiation sickness. The effects of gamma radiation on blood formation are shown. 3 figs., 6 refs. (author)

  16. Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage

    DEFF Research Database (Denmark)

    Holm, C; Thomsen, L L; Norgaard, A

    2017-01-01

    BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, ran......BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open...

  17. A Cohort Study of Preoperative Single Dose Versus Four Doses of Antibiotics for Patients With Non-Complicated Acute Appendicitis

    Directory of Open Access Journals (Sweden)

    Salah H. Al Janaby

    2017-02-01

    Full Text Available Objective: To Test the efficacy of single preoperative dose of Cefotaxime 1gm and Metronidazole 500mg in reducing the surgical site infections (SSIs after open appendectomy in patients with non-complicated appendicitis (NCA Place and Duration of Study: Al Hilla General Teaching Hospital, Babel Governorate-Iraq, from January 2013 to January 2014. Patients & Methods: 100 patients, who underwent appendectomy for NCA and fulfilled the selection criteria, were randomized into two groups. The patients in group A received a single dose of pre-operative antibiotics (Cefotaxime sodium and metronidazole, while the group B patients received three more dose of the same antibiotics postoperatively. Patients of both groups were followed-up for 30 days to assess the postoperative infective complications. Results: Group A had 48, while group B comprised of 52 patients. The groups were comparable in the baseline characteristics. Statistically, P value in rates of SSIs between both the groups was 0.9182. None of the patients developed intra-abdominal collection. Conclusion: Single dose of pre-operative antibiotics (Cefotaxime and metronidazole was sufficient in reducing the SSIs after appendectomy for NPA. Postoperative antibiotics did not add an appreciable clinical benefit in these patients. Key words: Preoperative antibiotics, Appendectomy, Surgical site infection, Non-complicated appendicitis Abbreviations: SSI: Surgical Site Infection, NCA: non-complicated appendicitis CDC Center of Disease Control.

  18. Protect Patients by Using Single- and Multi-Dose Vials Correctly

    Centers for Disease Control (CDC) Podcasts

    2014-07-10

    CDC’s One & Only Campaign urges healthcare providers to recognize the differences between single-dose and multi-dose vials, and to understand appropriate use of each container type.  Created: 7/10/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 7/10/2014.

  19. Immunogenicity of fractional doses of tetravalent a/c/y/w135 meningococcal polysaccharide vaccine: results from a randomized non-inferiority controlled trial in Uganda.

    Directory of Open Access Journals (Sweden)

    Philippe J Guerin

    Full Text Available Neisseria meningitidis serogroup A is the main causative pathogen of meningitis epidemics in sub-Saharan Africa. In recent years, serogroup W135 has also been the cause of epidemics. Mass vaccination campaigns with polysaccharide vaccines are key elements in controlling these epidemics. Facing global vaccine shortage, we explored the use of fractional doses of a licensed A/C/Y/W135 polysaccharide meningococcal vaccine.We conducted a randomized, non-inferiority trial in 750 healthy volunteers 2-19 years old in Mbarara, Uganda, to compare the immune response of the full dose of the vaccine versus fractional doses (1/5 or 1/10. Safety and tolerability data were collected for all subjects during the 4 weeks following the injection. Pre- and post-vaccination sera were analyzed by measuring serum bactericidal activity (SBA with baby rabbit complement. A responder was defined as a subject with a > or =4-fold increase in SBA against a target strain from each serogroup and SBA titer > or =128. For serogroup W135, 94% and 97% of the vaccinees in the 1/5- and 1/10-dose arms, respectively, were responders, versus 94% in the full-dose arm; for serogroup A, 92% and 88% were responders, respectively, versus 95%. Non-inferiority was demonstrated between the full dose and both fractional doses in SBA seroresponse against serogroups W135 and Y, in total population analysis. Non-inferiority was shown between the full and 1/5 doses for serogroup A in the population non-immune prior to vaccination. Non-inferiority was not shown for any of the fractionate doses for serogroup C. Safety and tolerability data were favourable, as observed in other studies.While the advent of conjugate A vaccine is anticipated to largely contribute to control serogroup A outbreaks in Africa, the scale-up of its production will not cover the entire "Meningitis Belt" target population for at least the next 3 to 5 years. In view of the current shortage of meningococcal vaccines for Africa

  20. Vaccine hesitancy among parents of adolescents and its association with vaccine uptake.

    Science.gov (United States)

    Roberts, James R; Thompson, David; Rogacki, Brianna; Hale, Jessica J; Jacobson, Robert M; Opel, Douglas J; Darden, Paul M

    2015-03-30

    Addressing parental vaccine hesitancy may increase adolescent vaccination acceptance. However, no validated measure exists to identify parents hesitant toward adolescent vaccines. To determine if a modified version of the Parent Attitudes about Childhood Vaccines (PACV) survey, a previously validated tool to identify parental hesitancy toward vaccines in infants, predicts adolescent vaccine uptake at office visits. We modified the PACV for use in the adolescent setting and distributed it to a convenience sample of parents of adolescents aged 11 to 17 presenting for care at a diverse group of six pediatric practices in Oklahoma and South Carolina. We determined the vaccination status of the parents' adolescents for 3 vaccines (Tetanus-diphtheria-acellular pertussis [Tdap], meningococcal conjugate [MCV4], and human papillomavirus [HPV] vaccines). We used Fisher's exact tests to compare vaccination status with each survey item and with an overall general hesitancy scale that we constructed. We analyzed 363 surveys. At the time of the visit, vaccination coverage was 84% for Tdap, 73% for MCV, and 45% for any dose of HPV. Thirty-nine percent of parents expressed concern about vaccine efficacy and 41% expressed concern about side effects. Forty-five percent of parents disagreed with the statement that "teens can get all of the vaccines that are due at a single visit." Two individual items were associated with not receiving a dose of HPV vaccine that was due. The overall modified PACV score failed to predict adolescent vaccine uptake at an office visit. Several individual items were associated with vaccine uptake. The cumulative modified PACV, a general measure of vaccine hesitancy, was not associated with vaccination status despite illuminating parental hesitancy. We need to better understand vaccine-specific concerns for the adolescent population. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Linda X.; Garg, Madhur; Lasala, Patrick; Kim, Mimi; Mah, Dennis; Chen, Chin-Cheng; Yaparpalvi, Ravindra; Mynampati, Dinesh; Kuo, Hsiang-Chi; Guha, Chandan; Kalnicki, Shalom [Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Neurosurgery, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Epidemiology and Population Health, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States)

    2011-03-15

    Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems, Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group

  2. Single subcutaneous dosing of cefovecin in rhesus monkeys (Macaca mulatta)

    DEFF Research Database (Denmark)

    Bakker, J.; Thuesen, Line Risager; Braskamp, G.

    2011-01-01

    was to determine whether cefovecin is a suitable antibiotic to prevent skin wound infection in rhesus monkeys. Therefore, the pharmacokinetics (PK) of cefovecin after a single subcutaneous injection at 8 mg/kg bodyweight in four rhesus monkeys (Macaca mulatta) and sensitivity of bacterial isolates from fresh skin...... wounds were determined. After administration, blood, urine, and feces were collected, and concentrations of cefovecin were determined. Further, the minimum inhibitory concentrations (MIC) for bacteria isolated from fresh skin wounds of monkeys during a health control program were determined. The mean...... maximum plasma concentration (C(max) ) of cefovecin was 78 µg/mL and was achieved after 57 min. The mean apparent long elimination half-life (t½) was 6.6 h and excretion occurred mainly via urine. The MIC for the majority of the bacteria examined was >100 µg/mL. The PK of cefovecin in rhesus monkeys...

  3. A simulation study on the dose distribution for a single beam of the gamma knife

    International Nuclear Information System (INIS)

    Chen, Chin-cheng; Jiang, Shiang-Huei; Lee, Chung-chi; Shiau, Cheng-Ying

    2000-01-01

    The purpose of this study is to evaluate the impact of the tissue heterogeneity on the dose distribution for a single beam of the gamma knife. The EGS4 Monte Carlo code was used to simulate both depth and radial profiles of the radiation dose in homogeneous and heterogeneous phantoms, respectively. The results are compared with the dose distribution calculated using the mathematical model of Gamma Plan, the treatment planning system of the gamma knife. The skull and sinus heterogeneity were simulated by a Teflon shell and an air shell, respectively. It was found that the tissue heterogeneity caused significant perturbation on the absolute depth dose at the focus as well as on the depth-dose distribution near the phantom surface and/or at the interface but little effect on the radial dose distribution. The effect of the beam aperture on the depth-dose distribution was also investigated in this study. (author)

  4. Coverage, efficacy or dosing interval: which factor predominantly influences the impact of routine childhood vaccination for the prevention of varicella? A model-based study for Italy

    Directory of Open Access Journals (Sweden)

    Katsiaryna Holl

    2016-10-01

    Full Text Available Abstract Background Varicella is a highly infectious disease with a significant public health and economic burden, which can be prevented with childhood routine varicella vaccination. Vaccination strategies differ by country. Some factors are known to play an important role (number of doses, coverage, dosing interval, efficacy and catch-up programmes, however, their relative impact on the reduction of varicella in the population remains unclear. This paper aims to help policy makers prioritise the critical factors to achieve the most successful vaccination programme with the available budget. Methods Scenarios assessed the impact of different vaccination strategies on reduction of varicella disease in the population. A dynamic transmission model was used and adapted to fit Italian demographics and population mixing patterns. Inputs included coverage, number of doses, dosing intervals, first-dose efficacy and availability of catch-up programmes, based on strategies currently used or likely to be used in different countries. The time horizon was 30 years. Results Both one- and two-dose routine varicella vaccination strategies prevented a comparable number of varicella cases with complications, but two-doses provided broader protection due to prevention of a higher number of milder varicella cases. A catch-up programme in susceptible adolescents aged 10–14 years old reduced varicella cases by 27–43 % in older children, which are often more severe than in younger children. Coverage, for all strategies, sustained at high levels achieved the largest reduction in varicella. In general, a 20 % increase in coverage resulted in a further 27–31 % reduction in varicella cases. When high coverage is reached, the impact of dosing interval and first-dose vaccine efficacy had a relatively lower impact on disease prevention in the population. Compared to the long (11 years dosing interval, the short (5 months and medium (5 years interval schedules

  5. Correlation between the single, high dose of ingested baclofen and clinical symptoms

    Directory of Open Access Journals (Sweden)

    Jacek Sein Anand

    2017-12-01

    There is a statistically significant correlation between the dose of ingested baclofen and the presence of acute respiratory failure, and duration of mechanical ventilation. Patients who have taken a single dose of baclofen of 200 mg, or higher, should be managed in centres able to provide continuous monitoring of life functions. Those with a higher level of a single dose of baclofen ingestion (>500 mg, should be hospitalized in a Toxicology Unit or Intensive Care Unit able to provide airway support and mechanical ventilation.

  6. Developing a single-aliquot protocol for measuring equivalent dose in biogenic carbonates

    International Nuclear Information System (INIS)

    Stirling, R.J.; Duller, G.A.T.; Roberts, H.M.

    2012-01-01

    Exploiting biogenic carbonates as thermoluminescence dosimeters requires an understanding of trap kinetics and an appropriate sequence with which to measure equivalent dose. The trap kinetics of two high temperature peaks (peaks II and III) from calcitic snail opercula have been investigated resulting in the calculation of lifetimes of 7.4 × 10 7 and 1.4 × 10 11 years for the two peaks respectively. Two measurement sequences, based upon changes in the application and measurement of a test dose, have been applied to peaks II and III, and though both methods were equally successful in dose recovery and production of a dose response curve some differences were observed. Primarily, the use of method 1 lead to dose dependant sensitivity change implying competition effects occurring during irradiation; method 2 did not experience this phenomenon. As a consequence method 2 was chosen as the most appropriate protocol for single-aliquot dating of this material. When assessing the TL behaviour of the two peaks, peak II performed poorly in dose recovery experiments recovering a dose 60–100% larger than that applied. Disproportionate growth of peak II in response to a beta dose applied prior to measurement, compared to growth following regeneration doses indicated that peak II was not suitable for use in single-aliquot protocols. However, dose recovery results for peak III were all within errors of unity of the given dose, and peak III was therefore chosen as the most appropriate peak for TL dosimetry in these single-aliquot procedures. The lifetime of charge in peak III is sufficient to date over many millions of years, and furthermore using the chosen method 2 the dose response curve has a D 0 of 3,250 ± 163 Gy allowing dating to over 3 million years.

  7. Addition of αGal HyperAcute™ technology to recombinant avian influenza vaccines induces strong low-dose antibody responses.

    Directory of Open Access Journals (Sweden)

    Wenlan Alex Chen

    Full Text Available Highly pathogenic avian influenza represents a severe public health threat. Over the last decade, the demand for highly efficacious vaccines against avian influenza viruses has grown, especially after the 2013 H7N9 outbreak in China that resulted in over 600 human cases with over 200 deaths. Currently, there are several H5N1 and H7N9 influenza vaccines in clinical trials, all of which employ traditional oil-in-water adjuvants due to the poor immunogenicity of avian influenza virus antigens. In this study, we developed potent recombinant avian influenza vaccine candidates using HyperAcute™ Technology, which takes advantage of naturally-acquired anti-αGal immunity in humans. We successfully generated αGal-positive recombinant protein and virus-like particle vaccine candidates of H5N1 and H7N9 influenza strains using either biological or our novel CarboLink chemical αGal modification techniques. Strikingly, two doses of 100 ng αGal-modified vaccine, with no traditional adjuvant, was able to induce a much stronger humoral response in αGT BALB/c knockout mice (the only experimental system readily available for testing αGal in vivo than unmodified vaccines even at 10-fold higher dose (1000 ng/dose. Our data strongly suggest that αGal modification significantly enhances the humoral immunogenicity of the recombinant influenza vaccine candidates. Use of αGal HyperAcute™ technology allows significant dose-sparing while retaining desired immunogenicity. Our success in the development of highly potent H5N1 and H7N9 vaccine candidates demonstrated the potential of αGal HyperAcute™ technology for the development of vaccines against other infectious diseases.

  8. Low-dose ketoconazole-fluconazole combination versus fluconazole in single doses for the treatment of vaginal candidiasis

    Directory of Open Access Journals (Sweden)

    Jan Susilo

    2011-08-01

    Full Text Available Background: Vaginal candidiasis (VC is one of the most common fungal diseases. Candida albicans is the most common causative fungus and has been isolated from more than 80% of specimens obtained from women with VC. Ketoconazole is the first orally active antifungal, the dosage for VC is 200 mg twice daily for 5 days. Fluconazole is the newer oral antifungal, its dosage for VC is a single oral dose of 150 mg. Since fluconazole 150 mg is considerably expensive, a single dose of 100 mg ketoconazole and 40 mg fluconazole in combination has been tested for the treatment of VC. The results showed that from 11 women with confirmed VC, 1-2 weeks after drug administration, the mycological culture was negative in 8 women, positive in 1 woman, and 2 woman lost to follow-up. This promising result led to the present study with the objective to confirm the efficacy and safety of the above combination in a formal clinical trial.Methods: A total of 165 female patients, aged 18 years or older, with the diagnosis of VC from clinical symptoms (pruritus or burning or excessive discharge and positive microscopic smear (pseudohyphae and/or yeast cells were randomized to receive a single dose of either keto-fluco combination (n = 85 or fluconazole (n = 80, and returnedfor follow-up visit on day 8.Results: Among these patients, 39 patients had negative baseline culture, leaving 126 patients eligible for efficacy evaluation. The mycological eradication in the keto-fluco group was 74.5% (41 patients from a total of 55 patients with available mycological culture, while that in the fluconazole group was 70.2% (40 patients from 57 patients with available culture and this difference was not significant. The clinical favorable response (clinical cure and clinical improvement in the keto-fluco arm (n = 60 was 98.3%, while that in the fluconazole group (n = 66 was 100%. Adverse events were found in 5 patients, 3 patients in the keto-fluco group (3/85 = 3.5% and 2

  9. Persistence of the immune response after MenACWY-CRM vaccination and response to a booster dose, in adolescents, children and infants.

    Science.gov (United States)

    Baxter, Roger; Keshavan, Pavitra; Welsch, Jo Anne; Han, Linda; Smolenov, Igor

    2016-05-03

    Persistence of bactericidal antibodies following vaccination is extremely important for protection against invasive meningococcal disease, given the epidemiology and rapid progression of meningococcal infection. We present an analysis of antibody persistence and booster response to MenACWY-CRM, in adolescents, children and infants, from 7 clinical studies. Immunogenicity was assessed using the serum bactericidal assay with both human and rabbit complement. Post-vaccination hSBA titers were high, with an age- and serogroup-specific decline in titers up to 1 y and stable levels up to 5 y The waning of hSBA titers over time was more pronounced among infants and toddlers and the greatest for serogroup A. However, rSBA titers against serogroup A were consistently higher and showed little decline over time, suggesting that protection against this serogroup may be sustained. A single booster dose of MenACWY-CRM administered at 3 to 5 y induced a robust immune response in all age groups.

  10. Protective immune response of oral rabies vaccine in stray dogs, corsacs and steppe wolves after a single immunization.

    Science.gov (United States)

    Zhugunissov, K; Bulatov, Ye; Taranov, D; Yershebulov, Z; Koshemetov, Zh; Abduraimov, Ye; Kondibayeva, Zh; Samoltyrova, A; Amanova, Zh; Khairullin, B; Sansyzbay, A

    2017-11-01

    In this study the safety and protective immunity of an oral rabies vaccine, based on the live, modified rabies virus strain VRC-RZ2, was examined in stray dogs (Canis Sp.), corsacs (Vulpes corsac) and steppe wolves (Canis lupus campestris). In the safety group (dogs, n=6; corsacs, n=3; wolves, n=3) which was vaccinated with a 10-times field dose/animal, no animals showed any signs of disease or changes in behavior or appetite during the period of clinical observation, similar to the animals in the negative control group. Saliva samples taken from animals prior and post (5 th and 10 th days) vaccination failed to demonstrate rabies virus antigen. Observations of immunogenicity in vaccinated carnivores (dogs, corsacs and wolves) during a 180 day period showed the titers of virus neutralizing antibodies (VNA) in the blood sera of vaccinated dogs to be within 0.59-1.37 IU/mL. On 14 days post vaccination (dpv), all the wild carnivores had detectable levels of neutralizing antibodies, with mean titers ranging from 0.50 ± 0.07 IU/mL (for wolves) to 0.59 ± 0.10 IU/mL (for corsacs). Weeks after vaccination, all the vaccinated wolves and corsacs had higher levels of neutralizing antibodies: 0.70 ± 0.10 - 0.71 ± 0.08 IU/mL at 30 dpv, 1.06 ± 0.08 - 1.28 ± 0.21 IU/mL at 60 dpv and 0.41 ± 0.09 - 047 ± 0.06 at 180 dpv. The highest level of VNA (˃1.0 IU/ml) was detected at 60 dpv, in all vaccinated animals. After challenge all vaccinated dogs remained healthy for 180 days. Control animals (unvaccinated dogs) developed symptoms of rabies on day 6 post administration of a virulent virus and died of rabies on days 11-13. Of note, the VNA titers in all the wild carnivores (corsacs and wolves) immunized with VRC-RZ2 were higher than 0.5 IU/ml (0.59 ± 0.11 IU/ml), even as early as 14 days post vaccination. These, presumably protective, titers of antibodies to rabies virus were present in the dogs and wild carnivores examined in this study for at

  11. Single event effects and total ionizing dose effects of typical VDMOSFET devices

    International Nuclear Information System (INIS)

    Lou Jianshe; Cai Nan; Liu Jiaxin; Wu Qinzhi; Wang Jia

    2012-01-01

    In this work, single event effects and total ionizing dose effects of typical VDMOSFET irradiated by 60 Co γ-rays and 252 Cf source were studied. The single event burnout and single event gate rupture (SEB/SEGR) effects were investigated, and the relationship between drain-source breakdown voltage and ionizing dose was obtained. The results showed that the VDMOSFET devices were sensitive to SEB and SEGR, and measures to improve their resistance to SEB and SEGR should be considered seriously for their space applications. The drain-source breakdown voltage was sensitive to total ionizing dose effects as the threshold voltage. In assessing the devices' resistance to the total ionizing dose effects, both the threshold voltage and the drain-source breakdown voltage should be taken into account. (authors)

  12. Determination of burial dose in incompletely bleached fluvial samples using single grains of quartz

    DEFF Research Database (Denmark)

    Thomsen, Kristina Jørkov; Murray, A.S.; Bøtter-Jensen, Lars

    2007-01-01

    We determine the burial dose in three known-age incompletely bleached fluvial samples using single grains of quartz. Estimation of burial dose in incompletely bleached samples requires that the characteristics of the well-bleached part of the distribution are known in order to distinguish between...... well-bleached and poorly bleached grains. It is especially important to investigate if the uncertainties assigned to individual estimates of dose adequately describe the observed variability in well-bleached dose distributions. We investigate this by quantifying the overdispersion in laboratory-bleached...

  13. Application of the luminescence single-aliquot technique for dose estimation in the Marmara Sea

    International Nuclear Information System (INIS)

    Tanir, Guenes; Sencan, Emine; Boeluekdemir, M. Hicabi; Tuerkoez, M. Burak; Tel, Eyuep

    2005-01-01

    The aim of this study is to obtain the equivalent dose, which is the important quantity for all the studies related to the use of luminescence in dating sediments. Recent advances in luminescence dating have led to increasing application of the technique to sediment from the depositional environmental samples. The sample used in this study is the active main fault sample that was collected from the Sea of Marmara in NW Turkey. Equivalent dose was measured using both the multiple-aliquots and the single-aliquot techniques. In this study single aliquot regeneration on additive dose (SARA) procedure was also used. The result obtained was not in agreement with the results evaluated from the multiple-aliquots procedure. So a simple modification was suggested for SARA procedure. In our modified procedure the calculated dose (D) values were obtained by using the additive dose protocol instead of regeneration protocol

  14. Single-dose-response curves of murine gastrointestinal crypt stem cells

    International Nuclear Information System (INIS)

    Masuda, K.; Withers, H.R.; Mason, K.A.; Chen, K.Y.

    1977-01-01

    Dose-response curves for the reproductive capacity of crypt stem cells of murine colonic, jejunal, and gastric mucosae exposed in situ to multifractionated gamma ray exposures were analyzed and single-dose-survival curves of these cells were constructed. The following conclusions were drawn: (1) The single-dose-response curves bend downward over a dose range of approximately 200 to 1500 rad; (2) cell death seems to be due to nonrepairable damage at doses less than 250 rad for colon, and 220 rad for jejunum; (3) there are 21, 110, and 140 stem cells per crypt of gastric, colonic, and jejunal mucosa, respectively; and (4) jejunal stem cells are the most radiosensitive and gastric mucosal stem cells are the most resistant

  15. Effect of Low-Dose (Single-Dose Magnesium Sulfate on Postoperative Analgesia in Hysterectomy Patients Receiving Balanced General Anesthesia

    Directory of Open Access Journals (Sweden)

    Arman Taheri

    2015-01-01

    Full Text Available Background and Aim. Aparallel, randomized, double blinded, placebo-controlled trial study was designed to assess the efficacy of single low dose of intravenous magnesium sulfate on post-total abdominal hysterectomy (TAH pain relief under balanced general anesthesia. Subject and Methods. Forty women undergoing TAH surgery were assigned to two magnesium sulfate (N=20 and normal saline (N=20 groups randomly. The magnesium group received magnesium sulfate 50 mg·kg−1 in 100 mL of normal saline solution i.v as single-dose, just 15 minutes before induction of anesthesia whereas patients in control group received 100 mL of 0.9% sodium chloride solution at the same time. The same balanced general anesthesia was induced for two groups. Pethidine consumption was recorded over 24 hours precisely as postoperative analgesic. Pain score was evaluated with Numeric Rating Scale (NRS at 0, 6, 12, and 24 hours after the surgeries. Results. Postoperative pain score was lower in magnesium group at 6, 12, and 24 hours after the operations significantly (P<0.05. Pethidine requirement was significantly lower in magnesium group throughout 24 hours after the surgeries (P=0.0001. Conclusion. Single dose of magnesium sulfate during balanced general anesthesia could be considered as effective and safe method to reduce postoperative pain and opioid consumption after TAH.

  16. Controllable dose: a discussion on the control of individual doses from single sources

    International Nuclear Information System (INIS)

    Clarke, R.H.

    1999-01-01

    Contaminated land is an issue of considerable interest in many countries. It arises as a result of accidental releases, as from Chernobyl, and from manmade activities including atmospheric testing of nuclear weapons. Contamination is also an historic liability from, for example, plants using radium, or from excessive effluent discharges. A particular issue at present is the decommissioning of nuclear facilities, old reactors and weapons fabrication facilities. These liabilities require the expenditure of considerable amounts of money and some people think that too much money is being, and will be, spent to achieve low levels of residual contamination. If contaminated land is not cleaned up there is public concern and in some countries there will be litigation, charging that the environmental risk is too great. These concerns have led to an increased pressure from some individuals to propose a threshold in the dose-response relationship in order to reduce the expenditure. It is true that, increasingly, our science is judged in the courts rather than by national academies os science. Judge and jury will decide on the issue of the threshold and it is they who must be convinced as to whether there are no risks at low doses of radiation. The issue is primarily in relation to public non occupational exposure, and because of the continuing lack of definitive scientific evidence, a new approach to protection could be considered (author)

  17. Controllable dose: a discussion on the control of individual doses from single sources

    International Nuclear Information System (INIS)

    Clarke, R.

    1999-01-01

    Contaminated land is an issue of considerable interest in many countries. It arises as a result of accidental releases, as from Chernobyl, and from manmade activities including atmospheric testing of nuclear weapons. Contamination is also an historic liability from, for example, plants using radium, or from excessive effluent discharges. A particular issue at present is the decommissioning of nuclear facilities, old reactors and weapons fabrication facilities. These liabilities require the expenditure of considerable amounts of money and some people think that too much money is being, and will be, spent to achieve low levels of residual contamination. If contaminated land is not cleaned up these is public concern and in some countries there will be litigation, charging that the environmental risk is too great. These concerns have led to an increased pressure from some individuals to propose a threshold in the dose-responses relationship in order to reduce the expenditure. It is true that, increasingly, our science is judged in the courts rather by national academies of sciences. Judge and jury decide on the issue to the threshold and it is they who must convinced as to whether there are no risks at low doses of radiation. The issue is primarily in relation to public not occupational exposure, and because of the continuing lack of definitive scientific evidence, a new approach to protection could be considered. (author)

  18. Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

    Science.gov (United States)

    Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

    2016-01-01

    The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in

  19. Evaluation and validation of a single-dilution potency assay based upon serology of vaccines containing diphtheria toxoid: statistical analysis

    NARCIS (Netherlands)

    Marsman FR; Akkermans AM; Hendriksen CFM; de Jong WH

    1993-01-01

    This document presents the results of a validation study to the use of a single dilution assay in potency testing of the diphtheria component of DPT-polio vaccines. Based on historical data of multi-dilution assays on 27 consecutive batches a simulation study was performed to test the actual

  20. Immunogenicity and safety of one dose of diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine (Repevax®) followed by two doses of diphtheria, tetanus and poliomyelitis vaccine (Revaxis®) in adults aged ≥ 40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years.

    Science.gov (United States)

    Dominicus, Rolf; Galtier, Florence; Richard, Patrick; Baudin, Martine

    2014-06-30

    The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years. This open-label, multicentre study was conducted in adults aged ≥ 40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥ 0.1IU/mL by seroneutralization assay [SNA]); tetanus (≥ 0.1IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥ 8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥ 5EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥ 0.01IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose. Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5-96.8); tetanus and poliomyelitis, 100% (CI: 98.8-100). Percentage of participants with an antibody titre ≥ 5EU/mL against pertussis antigens was ≥ 95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8-100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%). This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an

  1. Single and 30 fraction tumor control doses correlate in xenografted tumor models: implications for predictive assays

    International Nuclear Information System (INIS)

    Gerweck, Leo E.; Dubois, Willum; Baumann, Michael; Suit, Herman D.

    1995-01-01

    Purpose/Objective: In a previous publication we reported that laboratory assays of tumor clonogen number, in combination with intrinsic radiosensitivity measured in-vitro, accurately predicted the rank-order of single fraction 50% tumor control doses, in six rodent and xenografted human tumors. In these studies, tumor hypoxia influenced the absolute value of the tumor control doses across tumor types, but not their rank-order. In the present study we hypothesize that determinants of the single fraction tumor control dose, may also strongly influence the fractionaled tumor control doses, and that knowledge of tumor clonogen number and their sensitivity to fractionated irradiation, may be useful for predicting the relative sensitivity of tumors treated by conventional fractionated irradiation. Methods/Materials: Five tumors of human origin were used for these studies. Special care was taken to ensure that all tumor control dose assays were performed over the same time frame, i.e., in-vitro cells of a similar passage were used to initiate tumor sources which were expanded and used in the 3rd or 4th generation. Thirty fraction tumor control doses were performed in air breathing mice, under normal blood flow conditions (two fractions/day). The results of these studies have been previously published. For studies under uniformly (clamp) hypoxic conditions, tumors arising from the same transplantation were randomized into single or fractionated dose protocols. For estimation of the fractionated TCD50 under hypoxic conditions, tumors were exposed to six 5.4 Gy fractions (∼ 2 Gy equivalent under air), followed by graded 'top-up' dose irradiation for determination of the TCD50; the time interval between doses was 6-9 hours. The single dose equivalent of the six 5.4 Gy doses was used to calculate an extrapolated 30 fraction hypoxic TCD50. Results: Fractionation substantially increased the dose required for tumor control in 4 of the 5 tumors investigated. For these 4 tumors

  2. Schistosoma mansoni: radiation dose and morphologic integrity of schistosomules as factors for an effective cryopreserved live vaccine

    International Nuclear Information System (INIS)

    Lewis, F.A.; Stirewalt, M.; Leef, J.L.

    1984-01-01

    The effectiveness of a cryopreserved, irradiated schistosomule vaccine against an homologous Schistosoma mansoni cercarial challenge was tested in C57B1/6 mice. Highly significant levels of protection developed consistently when mice were immunized with the vaccine irradiated at 10-20 Krad, i.e., doses below that considered optimal for irradiated cercariae (50 Krad). Cryopreserved schistosomules irradiated at 10 or 20 Krad induced greater levels of protection than did schistosomules irradiated at 2, 5, 30, or 50 Krad. Protective immunity developed as early as 3 weeks post-immunization. When immunizing inocula were injected at various times post-thaw, or when schistosomule subpopulations of normal-appearing, damaged or dead organisms were injected, those populations which had appeared to sustain the least degree of damage were those most capable of stimulating protective immunity. These findings highlight the hazards of extrapolating conditions considered standard for an irradiated cercarial vaccine to one in which cryopreservation, for storage of the schistosomules, is an added stress

  3. Primary vaccination with low dose live dengue 1 virus generates a proinflammatory, multifunctional T cell response in humans.

    Directory of Open Access Journals (Sweden)

    Janet C Lindow

    Full Text Available The four dengue virus serotypes (DENV-1-DENV-4 have a large impact on global health, causing 50-100 million cases of dengue fever annually. Herein, we describe the first kinetic T cell response to a low-dose DENV-1 vaccination study (10 PFU in humans. Using flow cytometry, we found that proinflammatory cytokines, IFNγ, TNFα, and IL-2, were generated by DENV-1-specific CD4(+ cells 21 days post-DENV-1 exposure, and their production continued through the latest time-point, day 42 (p<0.0001 for all cytokines. No statistically significant changes were observed at any time-points for IL-10 (p = 0.19, a regulatory cytokine, indicating that the response to DENV-1 was primarily proinflammatory in nature. We also observed little T cell cross-reactivity to the other 3 DENV serotypes. The percentage of multifunctional T cells (T cells making ≥ 2 cytokines simultaneously increased with time post-DENV-1 exposure (p<0.0001. The presence of multifunctional T cells together with neutralizing antibody data suggest that the immune response generated to the vaccine may be protective. This work provides an initial framework for defining primary T cell responses to each DENV serotype and will enhance the evaluation of a tetravalent DENV vaccine.

  4. Effective dose comparison between stitched and single FOV in CBCT protocols for complete dental arcade

    International Nuclear Information System (INIS)

    Soares, Maria Rosangela; Batista, Wilson Otto; Antonio, Patricia Lara de; Caldas, Linda V.E.; Maia, Ana F.

    2015-01-01

    Objective: The objective of this study was to assess and compare protocols with a single field of view and multiple stitched field of view with a similar clinical purpose by means of effective dose value. Materials and methods: Measurements of absorbed dose were performed with thermoluminescent dosemeters inserted in the position of organs/tissues of a female anthropomorphic phantom and from these values the effective dose was calculated, utilizing weighting factor tissue-ICRP 103 (2007). Results: The results obtained in this study for effective dose are within the range of 43.1 µSv and 111.5 µSv for equipment using protocols with single FOV and in the range of 44.5 µSv and 236.2 µSv for equipments that using protocols with stitched field of view. Conclusions: In terms of the value of effective dose, stitched FOV protocols do not have any advantage over the single field of view protocols. This results suggest the necessity for knowledge of the exposure parameters and effective dose values associated with each image protocol. - Highlights: • The study relies on the comparison of two protocols with similar goals of CBCT: stitched protocols and single protocols. • The stitched FOV protocol is more specific and it is good option when want imaging only of some dental units. • In relation the effective dose, single FOV protocols presents advantage over the stitched FOV protocols. • Know the exposure parameters and effective dose values associated with each image protocol is necessity for request the best CBCT tomographic image

  5. Single-dose radiosurgical treatment for hepatic metastases - therapeutic outcome of 138 treated lesions from a single institution

    International Nuclear Information System (INIS)

    Habermehl, Daniel; Herfarth, Klaus K; Bermejo, Justo Lorenzo; Hof, Holger; Rieken, Stefan; Kuhn, Sabine; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

    2013-01-01

    Local ablative therapies such as stereotactically guided single-dose radiotherapy or helical intensity-modulated radiotherapy (tomotherapy) with high single-doses are successfully applied in many centers in patients with liver metastasis not suitable for surgical resection. This study presents results from more than 10 years of clinical experience and evaluates long-term outcome and efficacy of this therapeutic approach. From 1997 to 2009 a total of 138 intrahepatic tumors of 90 patients were irradiated with single doses of 17 to 30 Gy (median dose 24 Gy). Median age of the patients was 64 years (range 31–89 years). Most frequent underlying tumor histologies were colorectal adenocarcinoma (70 lesions) and breast cancer (27 lesions). In 35 treatment sessions multiple targets were simultaneously irradiated (up to four lesions at once). Local progression-free (PFS) and overall survival (OS) after treatment were investigated using uni- and multiple survival regression models. Median overall survival of all patients was 24.3 months. Local PFS was 87%, 70% and 59% after 6, 12 and 18 months, respectively. Median time to local progression was 25.5 months. Patients with a single lesion and no further metastases at time of RT had a favorable median PFS of 43.1 months according to the Kaplan-Meier estimator. The type of tumor showed a statistical significant influence on local PFS, with a better prognosis for breast cancer histology than for colorectal carcinoma in uni- and multiple regression analysis (p = 0.05). Multiple regression analysis revealed no influence of planning target volume (PTV), patient age and radiation dose on local PFS. Treatment was well tolerated with no severe adverse events. This study confirms safety of SBRT in liver lesions, with 6- and 12 months local control of 87% and 70%. The dataset represents the clinical situation in a large oncology setting, with many competing treatment options and heterogeneous patient characteristics

  6. A single intranasal immunization with a subunit vaccine formulation induces higher mucosal IgA production than live respiratory syncytial virus

    International Nuclear Information System (INIS)

    Garg, Ravendra; Theaker, Michael; Martinez, Elisa C.; Drunen Littel-van den Hurk, Sylvia van

    2016-01-01

    Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice. This indicates a potential reason as to why long-term immunity is not induced by RSV infection. The comparison also revealed that germinal center lymphocyte populations were higher in ∆F/TriAdj-vaccinated mice. Furthermore, ∆F/TriAdj induced higher gene expression of activation-induced cytidine deaminase (AID), as well as IL-6, IL-21, TGF-β cytokines, which are key players in IgA class switch recombination, ultimately leading to a sustained long-term memory response. - Highlights: •Immune responses to adjuvanted RSV F protein, ∆F/TriAdj, and RSV were compared. •∆F/TriAdj stimulates more local IgA production than RSV. •∆F/TriAdj induces more local IgA secreting memory B cells than RSV. •Germinal center lymphocyte populations are higher in ∆F/TriAdj-vaccinated mice. •∆F/TriAdj induces higher gene expression of AID, IL-6, IL-21, and TGF-β than RSV.

  7. A single intranasal immunization with a subunit vaccine formulation induces higher mucosal IgA production than live respiratory syncytial virus

    Energy Technology Data Exchange (ETDEWEB)

    Garg, Ravendra [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Theaker, Michael [Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Martinez, Elisa C. [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Microbiology & Immunology, University of Saskatchewan, Saskatoon, Canada SK S7N 5E3 (Canada); Drunen Littel-van den Hurk, Sylvia van, E-mail: sylvia.vandenhurk@usask.ca [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada)

    2016-12-15

    Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice. This indicates a potential reason as to why long-term immunity is not induced by RSV infection. The comparison also revealed that germinal center lymphocyte populations were higher in ∆F/TriAdj-vaccinated mice. Furthermore, ∆F/TriAdj induced higher gene expression of activation-induced cytidine deaminase (AID), as well as IL-6, IL-21, TGF-β cytokines, which are key players in IgA class switch recombination, ultimately leading to a sustained long-term memory response. - Highlights: •Immune responses to adjuvanted RSV F protein, ∆F/TriAdj, and RSV were compared. •∆F/TriAdj stimulates more local IgA production than RSV. •∆F/TriAdj induces more local IgA secreting memory B cells than RSV. •Germinal center lymphocyte populations are higher in ∆F/TriAdj-vaccinated mice. •∆F/TriAdj induces higher gene expression of AID, IL-6, IL-21, and TGF-β than RSV.

  8. Impact of Hepatitis A vaccination with a two-dose schedule in Panama: Results of epidemiological surveillance and time trend analysis.

    Science.gov (United States)

    Estripeaut, Dora; Contreras, Rodolfo; Tinajeros, Olga; Castrejón, Maria Mercedes; Shafi, Fakrudeen; Ortega-Barria, Eduardo; DeAntonio, Rodrigo

    2015-06-22

    In April 2007, Panama introduced Hepatitis A universal vaccination using a two-dose schedule (Havrix(®)junior; GSK Vaccines, Belgium). We assessed the impact of this hepatitis A vaccine three years after it was recommended for universal mass vaccination in Panama. Hepatitis A vaccination impact was assessed using two different approaches. The first approach used retrospective data (incidence and number of cases for all age groups), collected from the passive surveillance of the Epidemiologic Surveillance System of the Ministry of Health of hepatitis A and unspecified hepatitis before (2000-2006) and after (2008-2010) introduction of hepatitis A vaccine. The second approach was a prospective hospital-based active surveillance for hepatitis cases conducted in subjects (0-14 years) during 2009-2011 at three sentinel hospitals in Panama. Overall, the annual incidence of hepatitis A and unspecified hepatitis in 2008, 2009 and 2010 were 13.1, 7.9 and 3.7 per 100,000 subjects, lower than the baseline incidence of 51.1 per 100,000 subjects. In comparison to the mean baseline period (2000-2006), there was an 82% mean reduction in the overall hepatitis-related outcomes (hepatitis A and unspecified hepatitis) after vaccine introduction (2008-2010) in all age groups. In the hospital-based surveillance (2009-2011), of the 42 probable viral hepatitis A cases, nine cases were confirmed as acute hepatitis A (8 in 2009, 1 in 2010). Of these confirmed cases, two belonged to the targeted vaccine group (1-4 years) but were not vaccinated. Our study suggests that the introduction of two-dose hepatitis A vaccines in Panama has contributed to the reduction in the incidence of overall hepatitis-related outcomes for all age groups, suggesting herd protection. Additional monitoring is required to document a sustained long-term effect. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. An inactivated vaccine made from a U.S. field isolate of porcine epidemic disease virus is immunogenic in pigs as demonstrated by a dose-titration.

    Science.gov (United States)

    Collin, Emily A; Anbalagan, Srivishnupriya; Okda, Faten; Batman, Ron; Nelson, Eric; Hause, Ben M

    2015-03-15

    Porcine epidemic diarrhea virus (PEDV), a highly pathogenic and transmissible virus in swine, was first detected in the U.S. in May, 2013, and has caused tremendous losses to the swine industry. Due to the difficulty in isolating and growing this virus in cell culture, few vaccine studies using cell culture propagated PEDV have been performed on U.S. strains in pigs. Therefore, the objective of this study was to evaluate the humoral immune response to the selected inactivated PEDV vaccine candidate in a dose-titration manner. PEDV was isolated from a pig with diarrhea and complete genome sequencing found >99% nucleotide identity to other U.S. PEDV. Inactivated adjuvanted monovalent vaccines were administered intramuscularly to five week old pigs in a dose titration experimental design, ranging from 6.0-8.0 log10 tissue culture infective dose (TCID50/mL), to evaluate immunogenicity using a fluorescent foci neutralization assay (FFN), fluorescent microsphere immunoassay (FMIA), and enzyme-linked immunosorbent assay (ELISA) on sera. Pigs vaccinated with 8.0 log10 TCID50/mL inactivated virus showed significantly higher FFN titers as well as FMIA and ELISA values than 6.0 log10 TCID50/mL vaccinates and the negative controls. These results demonstrate the immunogenicity of a PEDV inactivated viral vaccine with a U.S. strain via dose-titration. A future vaccination-challenge study would illustrate the efficacy of an inactivated vaccine and help evaluate protective FFN titers and ELISA and FMIA responses.

  10. Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.

    Science.gov (United States)

    Flanagan, Shawn; Fang, Edward; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

    2014-09-01

    Tedizolid phosphate is a novel antibacterial under investigation for the treatment of gram-positive infections. This study was conducted to assess the pharmacokinetics, safety, and tolerability of intravenous tedizolid phosphate as well as the oral bioavailability of tedizolid phosphate. Double-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies. Single center in the United States (Covance Clinical Research Unit, Madison, WI) between September 2009 and January 2010. Ninety healthy volunteers. Single intravenous (IV) doses of tedizolid phosphate 50 mg (lead-in) and 100-400 mg. Single oral and IV dose of tedizolid phosphate 200 mg in crossover fashion. Multiple IV doses of tedizolid phosphate 200 and 300 mg for up to 7 days. A dose-dependent increase was observed in the maximum plasma concentration (1.2-5.1 μg/ml) and the area under the concentration-time curve (17.4-58.7 μg × hr/ml) of tedizolid (the microbiologically active moiety of tedizolid phosphate) after single IV doses of tedizolid phosphate 100-400 mg. Administration of IV tedizolid phosphate 200 mg once/day for 7 days resulted in minimal (28%) tedizolid accumulation. The absolute oral bioavailability of tedizolid after a single 200-mg dose of tedizolid phosphate was 91%; pharmacokinetic parameters of tedizolid were similar with oral and IV administration. Treatment-related adverse events occurred in 41% of subjects. Most adverse events were related to infusion site and became more frequent with multiple dosing. In an additional 3-day tolerability study, IV tedizolid phosphate 200 mg and placebo were similarly tolerated, based on visual infusion phlebitis scores. These results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes. © 2014 Cubist Pharmaceuticals. Pharmacotherapy

  11. Intradermally Administered Yellow Fever Vaccine at Reduced Dose Induces a Protective Immune Response: A Randomized Controlled Non-Inferiority Trial

    NARCIS (Netherlands)

    M.G. Roukens (Guy); A.C.Th.M. Vossen (Ann); P.J. Bredenbeek (Peter); J.T. van Dissel (Jaap); L.G. Visser (Leo)

    2008-01-01

    textabstractBackground:Implementation of yellow fever vaccination is currently hampered by limited supply of vaccine. An alternative route of administration with reduced amounts of vaccine but without loss of vaccine efficacy would boost vaccination programmes.Methods and Findings:A randomized,

  12. Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults.

    Science.gov (United States)

    Troy, Stephanie B; Kouiavskaia, Diana; Siik, Julia; Kochba, Efrat; Beydoun, Hind; Mirochnitchenko, Olga; Levin, Yotam; Khardori, Nancy; Chumakov, Konstantin; Maldonado, Yvonne

    2015-06-15

    Inactivated polio vaccine (IPV) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised populations. However, IPV is unaffordable for many developing countries. Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV, but prior studies, all using 20% of the standard dose used in intramuscular IPV, resulted in inferior antibody titers. We randomly assigned 231 adults with well-controlled human immunodeficiency virus infection at a ratio of 2:2:2:1 to receive 40% of the standard dose of IPV intradermally, 20% of the standard dose intradermally, the full standard dose intramuscularly, or 40% of the standard dose intramuscularly. Intradermal vaccination was done using the NanoPass MicronJet600 microneedle device. Baseline immunity was 87%, 90%, and 66% against poliovirus serotypes 1, 2, and 3, respectively. After vaccination, antibody titers increased a median of 64-fold. Vaccine response to 40% of the standard dose administered intradermally was comparable to that of the standard dose of IPV administered intramuscularly and resulted in higher (although not significantly) antibody titers. Intradermal administration had higher a incidence of local side effects (redness and itching) but a similar incidence of systemic side effects and was preferred by study participants over intramuscular administration. A 60% reduction in the standard IPV dose without reduction in antibody titers is possible through intradermal administration. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomised, and controlled dose investigation trial.

    Science.gov (United States)

    Rivera, Luis; Pedersen, Rasmus S; Peña, Lourdes; Olsen, Klaus J; Andreasen, Lars V; Kromann, Ingrid; Nielsen, Pernille I; Sørensen, Charlotte; Dietrich, Jes; Bandyopadhyay, Ananda S; Thierry-Carstensen, Birgit

    2017-07-01

    Cost and supply constraints are key challenges in the use of inactivated polio vaccine (IPV). Dose reduction through adsorption to aluminium hydroxide (Al) is a promising option, and establishing its effectiveness in the target population is a crucial milestone in developing IPV-Al. The aim of this clinical trial was to show the non-inferiority of three IPV-Al vaccines to standard IPV. In this phase 2, non-inferiority, observer-blinded, randomised, controlled, single-centre trial in the Dominican Republic, healthy infants aged 6 weeks, not previously polio vaccinated, were allocated after computer-generated randomisation by block-size of four, to receive one of four IPV formulations (three-times reduced dose [1/3 IPV-Al], five-times reduced dose [1/5 IPV-Al], ten-times reduced dose [1/10 IPV-Al], or IPV) intramuscularly in the thigh at 6, 10, and 14 weeks of age. The primary outcome was seroconversion for poliovirus types 1, 2, and 3 with titres more than or equal to four-fold higher than the estimated maternal antibody titre and more than or equal to 8 after three vaccinations. Non-inferiority was concluded if the lower two-sided 90% CI of the seroconversion rate difference between IPV-Al and IPV was greater than -10%. The safety analyses were based on the safety analysis set (randomly assigned participants who received at least one trial vaccination) and the immunogenicity analyses were based on the per-protocol population. This study is registered with ClinicalTrials.gov registration, number NCT02347423. Between Feb 2, 2015, and Sept 26, 2015, we recruited 824 infants. The per-protocol population included 820 infants; 205 were randomly assigned to receive 1/3 IPV-Al, 205 to receive 1/5 IPV-Al, 204 to receive 1/10 IPV-Al, and 206 to receive IPV. The proportion of individuals meeting the primary endpoint of seroconversion for poliovirus types 1, 2, and 3 was already high for the three IPV-Al vaccines after two vaccinations, but was higher after three vaccinations

  14. A comparative study of single-dose treatment of chancroid using thiamphenicol versus Azithromycin.

    Science.gov (United States)

    Belda, Walter; Di Chiacchio, Nilton G; Di Chiacchio, Nilton; Romiti, Ricardo; Criado, Paulo R; Velho, Paulo Eduardo N Ferreira

    2009-06-01

    A study was conducted in São Paulo, Brazil, to compare azithromycin with thiamphenicol for the single-dose treatment of chancroid. In all, 54 men with chancroid were tested. The etiology was determined by clinical characterization and direct bacterioscopy with Gram staining. None of the patients had positive serology or dark-field examination indicating active infection with Treponema pallidum. Genital infections due to Neisseria gonorrhoeae and herpes simplex virus were excluded by polymerase chain reaction testing. For 54 patients with chancroid, cure rates with single-dose treatment were 73% with azithromycin and 89% with thiamphenicol. HIV seropositivity was found to be associated with treatment failure (p=0.001). The treatment failed in all HIV positive patients treated with azithromycin (p=0.002) and this drug should be avoided in these co-infected patients. In the view of the authors, thiamphenicol is the most indicated single-dose regimen for chancroid treatment.

  15. Single-dose volume regulation algorithm for a gas-compensated intrathecal infusion pump.

    Science.gov (United States)

    Nam, Kyoung Won; Kim, Kwang Gi; Sung, Mun Hyun; Choi, Seong Wook; Kim, Dae Hyun; Jo, Yung Ho

    2011-01-01

    The internal pressures of medication reservoirs of gas-compensated intrathecal medication infusion pumps decrease when medication is discharged, and these discharge-induced pressure drops can decrease the volume of medication discharged. To prevent these reductions, the volumes discharged must be adjusted to maintain the required dosage levels. In this study, the authors developed an automatic control algorithm for an intrathecal infusion pump developed by the Korean National Cancer Center that regulates single-dose volumes. The proposed algorithm estimates the amount of medication remaining and adjusts control parameters automatically to maintain single-dose volumes at predetermined levels. Experimental results demonstrated that the proposed algorithm can regulate mean single-dose volumes with a variation of 98%. © 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  16. A comparative study of single-dose treatment of chancroid using thiamphenicol versus Azithromycin

    Directory of Open Access Journals (Sweden)

    Walter B. Junior

    Full Text Available A study was conducted in São Paulo, Brazil, to compare azithromycin with thiamphenicol for the single-dose treatment of chancroid. In all, 54 men with chancroid were tested. The etiology was determined by clinical characterization and direct bacterioscopy with Gram staining. None of the patients had positive serology or dark-field examination indicating active infection with Treponema pallidum. Genital infections due to Neisseria gonorrhoeae and herpes simplex virus were excluded by polymerase chain reaction testing. For 54 patients with chancroid, cure rates with single-dose treatment were 73% with azithromycin and 89% with thiamphenicol. HIV seropositivity was found to be associated with treatment failure (p=0.001. The treatment failed in all HIV positive patients treated with azithromycin (p=0.002 and this drug should be avoided in these co-infected patients. In the view of the authors, thiamphenicol is the most indicated single-dose regimen for chancroid treatment.

  17. Effect of propranolol in head tremor: quantitative study following single-dose and sustained drug administration.

    Science.gov (United States)

    Calzetti, S; Sasso, E; Negrotti, A; Baratti, M; Fava, R

    1992-12-01

    The effect of the beta-adrenoceptor antagonist propranolol has been investigated in nine patients suffering from isolated (six patients) or prominent (three patients) essential tremor of the head. In a double-blind, placebo-controlled study the tremorolytic efficacy of propranolol has been assessed by a quantitative accelerometric method after a single oral dose (120 mg) and following 2 weeks of sustained treatment with two different dosage regimens of the drug (120 and 240 mg daily). As compared with placebo, a significant reduction in tremor magnitude was found following a single oral dose but not on sustained administration of the beta-blocker at either dosage. The results suggest that the efficacy of sustained propranolol on isolated or prominent essential head tremor is less predictable and satisfactory than expected on the basis of the single-dose response, as compared with hand tremor.

  18. High-dose vitamin A with vaccination after 6 months of age

    DEFF Research Database (Denmark)

    Fisker, Ane B; Bale, Carlito; Rodrigues, Amabelia

    2014-01-01

    BACKGROUND: The World Health Organization recommends vitamin A supplementation (VAS) at routine vaccination contacts after 6 months of age based on the assumption that it reduces mortality by 24%. The policy has never been evaluated in randomized controlled trials for its effect on overall mortal...

  19. A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine

    DEFF Research Database (Denmark)

    Fisker, Ane B; Nebie, Eric; Schoeps, Anja

    2018-01-01

    Background: Besides protecting against measles, measles vaccine (MV) may have beneficial non-specific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods: Children aged 4-7 months in two rural health and demographic surveillance sites in Burki...

  20. Determinants of full valid vaccine dose administration among 12-32 ...

    African Journals Online (AJOL)

    unhcc

    Urban residence 2.6 (95% CI: 2.50, 2.68), mothers with age groups of 21-34 and >35 were 1.26 (95% CI: 1.22, ... adherence to vaccination schedule also has an effect on it. (2, 3). ..... well as knowledge, attitude and practice of service users in ...

  1. Vaccines and vaccination against yellow fever: WHO Position Paper, June 2013--recommendations.

    Science.gov (United States)

    2015-01-01

    This article presents the World Health Organizations (WHO) evidence and recommendations for the use of yellow fever (YF) vaccination from "Vaccines and vaccination against yellow fever: WHO Position Paper - June 2013" published in the Weekly Epidemiological Record. This position paper summarizes the WHO position on the use of YF vaccination, in particular that a single dose of YF vaccine is sufficient to confer sustained life-long protective immunity against YF disease. A booster dose is not necessary. The current document replaces the position paper on the use of yellow fever vaccines and vaccination published in 2003. Footnotes to this paper provide a number of core references. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its April 2013 meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html. Copyright © 2014. Published by Elsevier Ltd.

  2. A randomized trial of a standard dose of Edmonston-Zagreb measles vaccine given at 4.5 months of age: effect on total hospital admissions.

    Science.gov (United States)

    Martins, Cesario L; Benn, Christine S; Andersen, Andreas; Balé, Carlito; Schaltz-Buchholzer, Frederik; Do, Vu An; Rodrigues, Amabelia; Aaby, Peter; Ravn, Henrik; Whittle, Hilton; Garly, May-Lill

    2014-06-01

    Observational studies and trials from low-income countries indicate that measles vaccine has beneficial nonspecific effects, protecting against non-measles-related mortality. It is not known whether measles vaccine protects against hospital admissions. Between 2003 and 2007, 6417 children who had received the third dose of diphtheria, tetanus, and pertussis vaccine were randomly assigned to receive measles vaccine at 4.5 months or no measles vaccine; all children were offered measles vaccine at 9 months of age. Using hospital admission data from the national pediatric ward in Bissau, Guinea-Bissau, we compared admission rates between enrollment and the 9-month vaccination in Cox models, providing admission hazard rate ratios (HRRs) for measles vaccine versus no measles vaccine. All analyses were conducted stratified by sex and reception of neonatal vitamin A supplementation (NVAS). Before enrollment the 2 groups had similar admission rates. Following enrollment, the measles vaccine group had an admission HRR of 0.70 (95% confidence interval [CI], .52-.95), with a ratio of 0.53 (95% CI, .32-.86) for girls and 0.86 (95% CI, .58-1.26) for boys. For children who had not received NVAS, the admission HRR was 0.53 (95% CI, .34-.84), with an effect of 0.30 (95% CI, .13-.70) for girls and 0.73 (95% CI, .42-1.28) for boys (P = .08, interaction test). The reduction in admissions was separately significant for measles infection (admission HRR, 0 [95% CI, 0-.24]) and respiratory infections (admission HRR, 0.37 [95% CI, .16-.89]). Early measles vaccine may have major benefits for infant morbidity patterns and healthcare costs. Clinical trials registration NCT00168558.

  3. On the random distribution of scarce doses of vaccine in response to the threat of an influenza pandemic: a response to Wardrope.

    Science.gov (United States)

    McLachlan, Hugh V

    2015-02-01

    Wardrope argues against my proposed non-consequentialist policy for the distribution of scarce influenza vaccine in the face of a pandemic. According to him, even if one accepts what he calls my deontological ethical theory, it does not follow that we are required to agree with my proposed randomised allocation of doses of vaccine by means of a lottery. He argues in particular that I fail to consider fully the prophylactic role of vaccination whereby it serves to protect from infection more people than are vaccinated. He concludes that: 'The benefits and burdens of vaccination are provided impartially and far more effectively by targeted vaccination than impartial lotteries.' He has shown convincingly that this conclusion can be established in the case of his particular envisaged scenario. However, Wardrope gives no reason to suppose that, in the circumstances that we actually face, targeted vaccination would constitute impartial treatment of citizens in the UK. I readily agree with Wardrope that if it should treat its citizens justly and impartially, it does not necessarily follow that the state should distribute vaccinations of the basis of a lottery. That will be a reasonable thing to do only if certain assumptions are made. These assumptions will not always be reasonable. However, they are reasonable ones to make in the actual circumstances that currently apply. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Effective dose to staff from interventional procedures: Estimations from single and double dosimetry

    International Nuclear Information System (INIS)

    Kuipers, G.; Velders, X. L.

    2009-01-01

    The exposure of 11 physicians performing interventional procedures was measured by means of two personal dosemeters. One personal dosemeter was worn outside the lead apron and an additional under the lead apron. The study was set up in order to determine the added value of a dosemeter worn under the lead apron. With the doses measured, the effective doses of the physicians were estimated using an algorithm for single dosimetry and two algorithms for double dosimetry. The effective doses calculated with the single dosimetry algorithm ranged from 0.11 to 0.85 mSv in 4 weeks. With the double dosimetry algorithms, the effective doses ranged from 0.02 mSv to 0.47 mSv. The statistical analysis revealed no significant differences in the accuracy of the effective doses calculated with single or double dosimetry algorithms. It was concluded that the effective dose cannot be considered a more accurate estimate when two dosemeters are used instead of one. (authors)

  5. Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

    International Nuclear Information System (INIS)

    Leith, J.L.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Walton, R.E.; Woodruff, K.H.; Howard, J.

    1980-01-01

    The response of rat spinal cord to irradiation with accelerated heavy ions, in particular carbon and neon ions has been studied. Two different ionization regions in the modified Bragg curve for each ion have been studied for both single and fractionated exposures. We have defined the paralytic response as a function of dose and dose per fraction, and we have determined RBE and repair values. The response of rat spinal cord is both dose and LET dependent, which allows the derivation of RBE and repair values

  6. Variable dose rate single-arc IMAT delivered with a constant dose rate and variable angular spacing

    International Nuclear Information System (INIS)

    Tang, Grace; Earl, Matthew A; Yu, Cedric X

    2009-01-01

    Single-arc intensity-modulated arc therapy (IMAT) has gained worldwide interest in both research and clinical implementation due to its superior plan quality and delivery efficiency. Single-arc IMAT techniques such as the Varian RapidArc(TM) deliver conformal dose distributions to the target in one single gantry rotation, resulting in a delivery time in the order of 2 min. The segments in these techniques are evenly distributed within an arc and are allowed to have different monitor unit (MU) weightings. Therefore, a variable dose-rate (VDR) is required for delivery. Because the VDR requirement complicates the control hardware and software of the linear accelerators (linacs) and prevents most existing linacs from delivering IMAT, we propose an alternative planning approach for IMAT using constant dose-rate (CDR) delivery with variable angular spacing. We prove the equivalence by converting VDR-optimized RapidArc plans to CDR plans, where the evenly spaced beams in the VDR plan are redistributed to uneven spacing such that the segments with larger MU weighting occupy a greater angular interval. To minimize perturbation in the optimized dose distribution, the angular deviation of the segments was restricted to ≤± 5 deg. This restriction requires the treatment arc to be broken into multiple sectors such that the local MU fluctuation within each sector is reduced, thereby lowering the angular deviation of the segments during redistribution. The converted CDR plans were delivered with a single gantry sweep as in the VDR plans but each sector was delivered with a different value of CDR. For four patient cases, including two head-and-neck, one brain and one prostate, all CDR plans developed with the variable spacing scheme produced similar dose distributions to the original VDR plans. For plans with complex angular MU distributions, the number of sectors increased up to four in the CDR plans in order to maintain the original plan quality. Since each sector was

  7. Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

    Science.gov (United States)

    Arguedas, A; Soley, C; Loaiza, C; Rincon, G; Guevara, S; Perez, A; Porras, W; Alvarado, O; Aguilar, L; Abdelnour, A; Grunwald, U; Bedell, L; Anemona, A; Dull, P M

    2010-04-19

    This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity. Copyright 2010 Elsevier Ltd. All rights reserved.

  8. Response of mouse tongue epithelium to single doses of bleomycin and radiation

    International Nuclear Information System (INIS)

    Dorr, W.; Hirler, E.; Honig, M.

    1993-01-01

    Both bleomycin (BLM) and local X-irradiation (25 kV) induce denudation in the tongue epithelium of the C3H-Neuherberg mouse in a dose-dependent manner. In the present study the effect of BLM alone and of combined single doses of drug and radiation were studied using the incidence of epithelial denudation as the end-point. In 'time-line' experiments, 8 mg/kg BLM were given before or after graded doses of X-rays. BLM treatment required a reduction of the radiation dose (ED 50 ) from 15 Gy to 5-7 Gy, independent of sequence or time interval. In contrast, the time course of the response was clearly dependent on the treatment interval. Latency decreased when the drug was injected less than 2 h before irradiation with minimum latency observed at 30 min. Isobologram analysis of experiments with varying combinations of X-rays and BLM demonstrated that small drug doses were relatively more effective than larger doses, suggesting an upward concavity of the BLM dose-effective curve in vivo, i.e. a 'negative shoulder' of the curve in the low dose region. In contrast to the response to X-rays alone, which has a constant latent time to ulcer of 10 days, the latency in combined treatment was clearly shortened with increasing drug dose and at high doses eventually approximated the epithelial turnover time of 5 days. The data suggest that BLM both as a single agent and in combination with X-rays reduced the probability of abortive divisions and through this effect shortened the latent time to epithelial denudation. (author)

  9. The two-dose measles, mumps, and rubella (MMR) immunisation schedule: factors affecting maternal intention to vaccinate.

    OpenAIRE

    Pareek, M; Pattison, H M

    2000-01-01

    BACKGROUND: In the light of sub-optimal uptake of the measles, mumps, and rubella (MMR) vaccination, we investigated the factors that influence the intentions of mothers to vaccinate. METHOD: A cross-sectional survey of 300 mothers in Birmingham with children approaching a routine MMR vaccination was conducted using a postal questionnaire to measure: intention to vaccinate, psychological variables, knowledge of the vaccine, and socioeconomic status. The vaccination status of the children was ...

  10. Accelerated repopulation of mouse tongue epithelium during fractionated irradiations or following single doses

    International Nuclear Information System (INIS)

    Doerr, W.; Kummermehr, J.

    1990-01-01

    Mouse tongue mucosa was established as an animal model to study repopulation after large single doses or during continuous irradiation. A top-up irradiation technique was used employing priming doses or fractionated treatment to the whole snout (300 kV X-rays) followed by local test doses (25 kV X-rays) to elicit denudation in a confined field of the inferior tongue surface. Clearcut quantal dose-response curves of ulcer incidence were obtained to all protocols; animal morbidity, i.e. body weight loss was minimal. Repopulation following priming doses of 10 and 13 Gy started with a delay of at least 3 days and then progressed rapidly to nearly restore original tissue tolerance by day 11. During continuous fractionation over 1 to 3 weeks with 5 fractions/week and doses per fraction of 2.5, 3 and 3.5 Gy, repopulation was small in week one but subsequently increased to fully compensate the weekly dose at all dose levels. Additional measurements of cell density during a 4 weeks course of 5 x 3 Gy or 5 x 4 Gy per week showed only moderate depletion to 67% of the control figures. The fact that rapid repopulation is achieved at relatively moderate damage levels should be taken into account when the timing of a treatment split is considered. (author). 18 refs.; 7 figs.; 1 tab

  11. Comparison of scatter doses from a multislice and a single slice CT scanner

    International Nuclear Information System (INIS)

    Burrage, J. W.; Causer, D. A.

    2006-01-01

    During shielding calculations for a new multislice CT (MSCT) scanner it was found that the manufacturer's data indicated significantly higher external scatter doses than would be generated for a single slice CT (SSCT). Even allowing for increased beam width, the manufacturer's data indicated that the scatter dose per scan was higher by a factor of about 3 to 4. The magnitude of the discrepancy was contrary to expectations and also contrary to a statement by the UK ImPACT group, which indicated that when beam width is taken into account, the scatter doses should be similar. The matter was investigated by comparing scatter doses from an SSCT and an MSCT. Scatter measurements were performed at three points using a standard perspex CTDI phantom, and CT dose indices were also measured to compare scanner output. MSCT measurements were performed with a 40 mm wide beam, SSCT measurements with a 10 mm wide beam. A film badge survey was also performed after the installation of the MSCT scanner to assess the adequacy of lead shielding in the room. It was found that the scatter doses from the MSCT were lower than indicated by the manufacturer's data. MSCT scatter doses were approximately 4 times higher than those from the SSCT, consistent with expectations due to beam width differences. The CT dose indices were similar, and the film badge survey indicated that the existing shielding, which had been adequate for the SSCT, was also adequate for the MSCT

  12. Des vaccins à dose unique à la rescousse du bétail et des moyens ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    L'industrie de l'élevage est une industrie essentielle en Afrique, mais qui subit de grandes pertes en raison d'infections virales évitables. Ce projet vise à mettre un frein au problème. Les chercheurs mettront au point des vaccins prototypes, effectueront des tests sur le terrain et prendront les premières mesures pour ...

  13. Budget impact of polio immunization strategy for India: introduction of one dose of inactivated poliomyelitis vaccine and reductions in supplemental polio immunization.

    Science.gov (United States)

    Khan, M M; Sharma, S; Tripathi, B; Alvarez, F P

    2017-01-01

    To conduct a budget impact analysis (BIA) of introducing the immunization recommendations of India Expert Advisory Group (IEAG) for the years 2015-2017. The recommendations include introduction of one inactivated poliomyelitis vaccine (IPV) dose in the regular child immunization programme along with reductions in oral polio vaccine (OPV) doses in supplemental programmes. This is a national level analysis of budget impact of new polio immunization recommendations. Since the states of India vary widely in terms of size, vaccine coverage and supplemental vaccine needs, the study estimated the budget impact for each of the states of India separately to derive the national level budget impact. Based on the recommendations of IEAG, the BIA assumes that all children in India will get an IPV dose at 14 weeks of age in addition to the OPV and DPT (or Pentavalent-3) doses. Cost of introducing the IPV dose was estimated by considering vaccine price and vaccine delivery and administration costs. The cost savings associated with the reduction in number of doses of OPV in supplemental immunization were also estimated. The analysis used India-specific or international cost parameters to estimate the budget impact. Introduction of one IPV dose will increase the cost of vaccines in the regular immunization programme from $20 million to $47 million. Since IEAG recommends lower intensity of supplemental OPV vaccination, polio vaccine cost of supplemental programme is expected to decline from $72 million to $53 million. Cost of administering polio vaccines will also decline from $124 million to $105 million mainly due to the significantly lower intensity of supplemental polio vaccination. The net effect of adopting IEAG's recommendations on polio immunization turns out to be cost saving for India, reducing total polio immunization cost by $6 million. Additional savings could be achieved if India adopts the new policy regarding the handling of multi-dose vials after opening

  14. Safety and immune response to a challenge dose of hepatitis B vaccine in healthy children primed 10years earlier with hexavalent vaccines in a 3, 5, 11-month schedule: An open-label, controlled, multicentre trial in Italy.

    Science.gov (United States)

    Zanetti, Alessandro; Desole, Maria Giuseppina; Romanò, Luisa; d'Alessandro, Antonio; Conversano, Michele; Ferrera, Giuseppe; Panico, Maria Grazia; Tomasi, Alberto; Zoppi, Giorgio; Zuliani, Massimo; Thomas, Stéphane; Soubeyrand, Benoît; Eymin, Cécile; Lockhart, Stephen

    2017-07-13

    The strategy of vaccinating infants to prevent hepatitis B virus infection in adolescence or adulthood requires durable immunity. This study investigated responses to a challenge dose of monovalent hepatitis B vaccine in children primed with three doses of either Hexavac® or Infanrix hexa® 10years earlier during infancy. This open-label, controlled, multicentre study conducted in Italy, enrolled 751 healthy pre-adolescents (aged 11-13years) who were given either Hexavac (n=409) or Infanrix hexa (n=342) at 3, 5 and 11months of life. All participants received a challenge dose of a monovalent hepatitis B vaccine (HBVaxPro® 5µg). The concentrations of antibodies to hepatitis B surface antigen (anti-HBs) were measured before and 1month after the challenge dose. The analysis was descriptive and no formal hypothesis was tested. One month post-challenge, 331 participants in the Hexavac cohort [83.6%, 95% CI: 79.6; 87.1] and 324 in the Infanrix hexa cohort [96.4%, 95% CI: 93.8; 98.1] had anti-HBs concentrations ≥10mIU/mL. Before the challenge dose, an anti-HBs concentration of ≥10mIU/mL was found in 94 children in the Hexavac cohort [23.9%, 95% CI: 19.7; 28.4] and in 232 children in the Infanrix hexa cohort [69%, 95% CI: 63.8; 74.0]. Among children with a pre-challenge anti-HBs concentration of children (>80%) at least 10years after a two-dose primary and booster vaccination schedule with a hexavalent vaccine (Hexavac or Infanrix hexa). EudraCT Number: 2013-001602-28; clinicaltrials.gov: NCT02012998. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Bile duct evaluation of potential living liver donors with Gd-EOB-DTPA enhanced MR cholangiography: Single-dose, double dose or half-dose contrast enhanced imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kinner, Sonja, E-mail: Sonja.Kinner@uni-due.de [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Steinweg, Verena [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Maderwald, Stefan [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Radtke, Arnold; Sotiropoulos, Georgios [Department of General Surgery, University Hospital Essen (Germany); Forsting, Michael; Schroeder, Tobias [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany)

    2014-05-15

    Introduction: Detailed knowledge of the biliary anatomy is essential to avoid complications in living donor liver transplantation. The aim of this study was to determine the optimal dosage of Gd-EOB-DTPA for contrast-enhanced magnetic resonance cholangiography (ce-MRC) with reference to contrast-enhanced CT cholangiography (ce-CTC). Materials and methods: 30 potential living liver donors (PLLD) underwent both ce-CTC and ce-MRC. Ten candidates each received single, double or half-dose Gd-EOB-DTPA. Ce-MRC images with and without inversion recovery pulses (T1w ± IR) were acquired 20–30 min after intravenous contrast injection. Image data was quantitatively and qualitatively reviewed by two radiologists based on a on a 5-point scale. Data sets were compared using a Mann–Whitney-U-test or Wilcoxon-rank-sum-test. Kappa values were also calculated. Results: All image series provided sufficient diagnostic information both showing normal biliary anatomy and variant bile ducts. Ce-CTC showed statistically significant better results compared to all ce-MRC data sets. T1w MRC with single dose Gd-EOB-DTPA proved to be superior to half and double dose in subjective and objective evaluation without a statistically significant difference. Conclusions: Ce-MRC is at any dosage inferior to ce-CTC. As far as preoperative planning of bile duct surgery is focused on the central biliary anatomy, ce-MRC can replace harmful ce-CTC strategies, anyway. Best results were seen with single dose GD-EOB-DTPA on T1w MRC+IR.

  16. Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy

    Directory of Open Access Journals (Sweden)

    Feras Sendy

    2015-01-01

    Full Text Available Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67% received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225 of the patients. 28% (63/225 were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63 of failure received a second dose of methotrexate, and 37% (23/63 underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

  17. Failure rate of single dose methotrexate in managment of ectopic pregnancy.

    Science.gov (United States)

    Sendy, Feras; AlShehri, Eman; AlAjmi, Amani; Bamanie, Elham; Appani, Surekha; Shams, Taghreed

    2015-01-01

    Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67%)) received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225) of the patients. 28% (63/225) were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63) of failure received a second dose of methotrexate, and 37% (23/63) underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

  18. Study of Serologic Response Rate to Pertussis after Administration of the Third Dose of Pentavalent Vaccine in Children 12 Months Old in Karaj City, Iran

    Directory of Open Access Journals (Sweden)

    Reza Arjmand

    2018-02-01

    Full Text Available Background: After substitution of Pentavalent vaccine with diphtheria, tetanus, pertussis (DTP in the Iranian National Vaccination program with 3 Pentavalent (three times vaccination with Pentavalent vaccine at months 2, 4, and 6 in 2014 and the lack of published research in the field of immunogenicity of pertussis component of this vaccine, the efficacy of pertussis vaccine was studied 6 months after the last dose of Pentavalent vaccine in Iranian infants.  Materials and Methods: Five hundred blood samples were collected from healthy one-year-old children who attended 18 health care centers of Karaj, Iran for routine vaccination selected by cluster sampling (2016. Sampling checklists contained demographic information and risk factors. The blood samples were sent to the laboratory for determination of Immunoglobulin G (IgG and IgA anti-pertussis antibody titer by ELISA method. Data were analyzed by STATA software (version 14.0. Results: 82.7% (n=413 of children (95% confidence interval [CI]: 79.49-86.11 had IgG titer less than 16 IU/ml against pertussis (no immune response, and 17.3% (n=87 had equal or greater than 16 IU/ml IgG titer against pertussis (95% CI: 13.89-20.51. IgA titer against pertussis was less than 8U/ml in all cases. Anti-pertussis IgG geometric mean titer (GMT was 15.80 U/ml (95% CI: 15.26-16.36, and IgA GMT was 6.26 U/ml (95% CI: 6.22-6.30. There was not a significant correlation between titer of pertussis antibody and demographic factors. Conclusion: Based on low IgG titer in vaccinated children, immunogenicity of pentavalent vaccine in Iranian children needs more investigation. In this study, 100 % of children had negative serologic response (IgA

  19. Efficacy of Single-Dose and Triple-Dose Albendazole and Mebendazole against Soil-Transmitted Helminths and Taenia spp.: A Randomized Controlled Trial

    Science.gov (United States)

    Steinmann, Peter; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Jia-Xu; Hattendorf, Jan; Zhou, Hui; Zhou, Xiao-Nong

    2011-01-01

    Background The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. Methodology/Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. Conclusions/Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are

  20. Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

    Directory of Open Access Journals (Sweden)

    Cui Y

    2013-12-01

    Full Text Available Yimin Cui,1 Yan Song,2 Jessie Wang,2 Zhigang Yu,2 Alan Schuster,2 Yu Chen Barrett,2 Charles Frost2 1Peking University First Hospital, Beijing, People's Republic of China; 2Bristol-Myers Squibb, Princeton, NJ, USA Background: The pharmacokinetics (PK, pharmacodynamics (PD, and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods: Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9. The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results: PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion: Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. Keywords: apixaban, oral

  1. A luminescence imaging system for the routine measurement of single-grain OSL dose distributions

    DEFF Research Database (Denmark)

    Kook, Myung Ho; Lapp, Torben; Murray, Andrew

    2015-01-01

    the potential of an electron multiplying charge-coupled device (EMCCD), providing extremely low level light detection. We characterize the performance of the device by discussing reproducibility and evaluating uncertainties in OSL signals. Finally we derive a typical single grain natural dose distribution...

  2. Single dose of fluoxetine increases muscle activation in chronic stroke patients.

    NARCIS (Netherlands)

    van Genderen, Hanneke Irene; Nijlant, Juliette M.M.; van Putten, Michel Johannes Antonius Maria; Movig, Kris L.L.; IJzerman, Maarten Joost

    2009-01-01

    Objectives: This pilot study explores the influence of a single dose of fluoxetine (20 mg) on the muscle activation patterns and functional ability of the muscles in the lower part of the arm in chronic stroke patients. Methods: A crossover, placebo-controlled clinical trial was conducted in 10

  3. Vaginal bleeding following the use of a single dose of 1.5mg ...

    African Journals Online (AJOL)

    Introduction: Recent studies have shown that a single dose of 1.5 mg levonorgestrel is an effective and safe emergency contraceptive but detailed information on its menstrual side effects is lacking. This study assessed the vaginal bleeding patterns in healthy women who used the medication for emergency contraception.

  4. X-γ dose rate continuous monitor with wide range based on single-chip microcomputer

    International Nuclear Information System (INIS)

    Wu Debo; Ling Qiu; Guo Lanying; Yang Binhua

    2007-01-01

    This paper describes a concept about circuit designing of X-γ dose rate continuous monitor with wide range based on single-chip microcomputer, and also presents the design procedure of hardware and software, and gives several methods for solving the design procedure of hardware and software with emphasis. (authors)

  5. Sources of variability in OSL dose measurements using single grains of quartz

    DEFF Research Database (Denmark)

    Thomsen, Kristina Jørkov; Murray, A.S.; Bøtter-Jensen, L.

    2005-01-01

    spread. In this preliminary study, dose distributions have been studied using single grains of heated and laboratory irradiated quartz. By heating the sample, the contribution from incomplete zeroing was excluded and at the same time the sample was sensitised. The laboratory gamma irradiation...

  6. Single dose silodosin prior to voiding cystourethrogram: a pharmacological adjunct to enhance visualization of posterior urethra.

    Science.gov (United States)

    Nagathan, Deepak Sharanappa; Dalela, Divakar; Sankhwar, Satyanarayan; Goel, Apul; Dwivedi, Amod Kumar; Yadav, Rahul

    2014-03-04

    Voiding cystourethrogram (VCUG) is needed to ascertain the upper end of urethral stricture. Occasionally, a patient is unable to open the bladder neck with resultant failure of the test. Realizing the strong and prompt alpha antagonistic action of silodosin, we evaluated single 8 mg dose as a pharmacological adjunct prior to VCUG to overcome this problem.

  7. Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance

    NARCIS (Netherlands)

    Lamers, CTJ; Ramaekers, JG; Muntjewerff, ND; Sikkema, KL; Samyn, N; Read, NL; Brookhuis, KA; Riedel, WJ

    2003-01-01

    Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition,

  8. Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

    International Nuclear Information System (INIS)

    Healy, W.L.; Lo, T.C.; Covall, D.J.; Pfeifer, B.A.; Wasilewski, S.A.

    1990-01-01

    Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700 centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy

  9. Single-shot, high-dose rabbit ATG for rejection prophylaxis after kidney transplantation

    NARCIS (Netherlands)

    R. Zietse (Bob); E.P.M. van Steenberge (E. P M); C.J. Hesse (Cees); L.B. Vaessen (L.); J.N.M. IJzermans (Jan); W. Weimar (Willem)

    1993-01-01

    textabstractWe studied the effects of a single intravenous injection of rabbit ATG (RIVM, Bilthoven, The Netherlands) in a dose of 8 mg/kg body weight administered 6 h after kidney transplantation on graft survival, rejection incidence, T-cell subsets, and cost-effectiveness. A total of 58 (37

  10. Effects of a preovulatory single low dose of mifepristone on ovarian function

    NARCIS (Netherlands)

    van der Stege, Jolande G.; Pahl-van Beest, Elske H.; Beerthuizen, Rob J. C. M.; van Lunsen, Rik H. W.; Scholten, Piet C.; Bogchelman, Dick H.

    Objectives To investigate the effect of a single low dose of mifepristone on ovarian function, when administered in the preovulatory period. Methods Healthy women with regular menstrual cycles were studied during two consecutive menstrual cycles. Either mifepristone or placebo was given in a

  11. Evaluation of sphingolipids in Wistar rats treated to prolonged and single oral doses of fumonisin b₁.

    Science.gov (United States)

    Direito, Glória M; Almeida, Adriana P; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

    2009-01-01

    The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B(1) (FB(1)). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB(1). Prolonged exposure to FB(1) caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB(1). Animals receiving a single dose of FB(1) presented variations in Sa and So levels and in the Sa/So ratio.

  12. Vaccination coverage and mortality after splenectomy: results from an Italian single-centre study.

    Science.gov (United States)

    Di Sabatino, Antonio; Lenti, Marco Vincenzo; Tinozzi, Francesco Paolo; Lanave, Marina; Aquino, Ivana; Klersy, Catherine; Marone, Piero; Marena, Carlo; Pietrabissa, Andrea; Corazza, Gino Roberto

    2017-12-01

    Splenectomy is a well-recognised risk factor for life-threatening overwhelming post-splenectomy infection (OPSI). To prevent OPSI, immunisations against encapsulated bacteria (S. pneumoniae, N. meningitidis, H. influenzae) and influenza virus are recommended. However, there is still a lack of uniformity and poor compliance with these recommendations. Following a local physicians' awareness campaign regarding the importance of vaccine prophylaxis of splenectomised patients, we aimed to register vaccination coverage, mortality and infection rates in all patients who underwent splenectomy at our hospital, over a six-year time span. Reasons for splenectomy, patients' compliance with vaccinations, mortality and infectious events were recorded. The reasons for splenectomy in the 216 identified patients (mean age 58.2 ± 14; M:F ratio 1.4:1) were haematologic disorders (38.8%), solid tumours (28.7%), traumatic rupture (22.7%) and other causes (9.7%). A total of 146 patients (67.6%) received at least one of the four vaccines. Overall, the mortality rate was significantly greater in unvaccinated compared to vaccinated patients (p splenectomy the statistical significance was lost (p = 0.085) due to the burden of solid tumour-related mortality. Among the 21 reported cases of OPSI, eight were fatal and five were potentially vaccine-preventable. Our results show that two-thirds of splenectomised patients comply with vaccine prophylaxis. Future interventional studies or ad hoc registries might overcome barriers to vaccination or intentional non-compliance.

  13. Longitudinal multiparameter single-cell analysis of macaques immunized with pneumococcal protein-conjugated or unconjugated polysaccharide vaccines reveals distinct antigen specific memory B cell repertoires.

    Directory of Open Access Journals (Sweden)

    Bin Jia

    Full Text Available The efficacy of protein-conjugated pneumococcal polysaccharide vaccines has been well characterized for children. The level of protection conferred by unconjugated polysaccharide vaccines remains less clear, particularly for elderly individuals who have had prior antigenic experience through immunization with unconjugated polysaccharide vaccines or natural exposure to Streptococcus pneumoniae.We compared the magnitude, diversity and genetic biases of antigen-specific memory B cells in two groups of adult cynomolgus macaques that were immunized with a 7-valent conjugated vaccine and boosted after five years with either a 13-valent pneumococcal polysaccharide conjugate vaccine (13vPnC or a 23-valent unconjugated pneumococcal polysaccharide vaccine (23vPS using microengraving (a single-cell analysis method and single-cell RT-PCR.Seven days after boosting, the mean frequency of antigen-specific memory B cells was significantly increased in macaques vaccinated with 13vPnC compared to those receiving 23vPS. The 13vPnC-vaccinated macaques also exhibited a more even distribution of antibody specificities to four polysaccharides in the vaccine (PS4, 6B, 14, 23F that were examined. However, single-cell analysis of the antibody variable region sequences from antigen-specific B cells elicited by unconjugated and conjugated vaccines indicated that both the germline gene segments forming the heavy chains and the average lengths of the Complementary Determining Region 3 (CDR3 were similar.Our results confirm that distinctive differences can manifest between antigen-specific memory B cell repertoires in nonhuman primates immunized with conjugated and unconjugated pneumococcal polysaccharide vaccines. The study also supports the notion that the conjugated vaccines have a favorable profile in terms of both the frequency and breadth of the anamnestic response among antigen-specific memory B cells.

  14. A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis.

    Science.gov (United States)

    Yasuda, Mitsuru; Ito, Shin; Kido, Akira; Hamano, Kiminari; Uchijima, Yutaka; Uwatoko, Noriyasu; Kusuyama, Hiroyuki; Watanabe, Akiko; Miyamura, Ryuzou; Miyata, Kazutoyo; Deguchi, Takashi

    2014-11-01

    We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability. We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients. We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild. The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Single-dose and multiple-dose pharmacokinetics and dose proportionality of intravenous and intramuscular HPβCD-diclofenac (Dyloject) compared with other diclofenac formulations.

    Science.gov (United States)

    Mermelstein, Fred; Hamilton, Douglas A; Wright, Curtis; Lacouture, Peter G; Ramaiya, Atulkumar; Carr, Daniel B

    2013-10-01

    To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. Clinical research center. Healthy adult volunteers. Study 1: Subjects received HPβCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPβCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. Study 1: IV HPβCD-diclofenac had a higher peak plasma concentration (Cmax ) and earlier time to reach maximum plasma concentration (Tmax ), but equivalent plasma exposure (area under the curve from time zero to t [AUC0-t ]) to IV Voltarol. The geometric mean ratio of HPβCD-diclofenac (IV) to Voltarol (IV) for AUC0-t was 106.27%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IM) for AUC0-t was 110.91%. The geometric mean ratio of HPβCD-diclofenac (IV) to HPβCD-diclofenac (IM) for AUC0-t was 101.25%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IV) for AUC0-t was 104.96%. Study 2: Cmax for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPβCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ng·hour/ml) and 37.5 mg (1843 ng·hour/ml) IV HPβCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ng·hour/ml). Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HP

  16. Study on relations between heavy ions single event upset cross sections and γ accumulated doses

    International Nuclear Information System (INIS)

    He Chaohui; Geng Bin; Wang Yanping; Peng Honglun; Yang Hailiang; Chen Xiaohua; Li Guozheng

    2002-01-01

    Experiments were done under 252 Cf and 60 Co γ source to study the relation between heavy ion Single Event Upset (SEU) cross sections and γ accumulated doses. There was no obvious rule and little influence of γ accumulated doses on SEU cross sections when Static Random Access Memories were in power off mode and static power on mode. In active measuring mode, the SEU cross section increased as the accumulated doses increasing when same data were written in memory cells. If reverse data, such as '55' and 'AA', were written in memory cells during the experiment, the SEU cross sections decreased to the level when memories were not irradiated under 60 Co γ source, even more small. It implied that the influence of γ accumulated doses on SEU cross sections can be set off by this method

  17. Dose performance and image quality: Dual source CT versus single source CT in cardiac CT angiography

    International Nuclear Information System (INIS)

    Wang Min; Qi Hengtao; Wang Ximing; Wang Tao; Chen, Jiu-Hong; Liu Cheng

    2009-01-01

    Objective: To evaluate dose performance and image quality of 64-slice dual source CT (DSCT) in comparison to 64-slice single source CT (SSCT) in cardiac CT angiography (CTA). Methods: 100 patients examined by DSCT and 60 patients scanned by SSCT were included in this study. Objective indices such as image noise, contrast-to-noise ratio and signal-to-noise ratio were analyzed. Subjective image quality was assessed by two cardiovascular radiologists in consensus using a four-point scale (1 = excellent to 4 = not acceptable). Estimation of effective dose was performed on the basis of dose length product (DLP). Results: At low heart rates ( 0.05), but, at high heart rates (>70 bpm), DSCT provided robust image quality (P 70 bpm), DSCT is able to provide robust diagnostic image quality at doses far below that of SSCT.

  18. A Lactococcus lactis BFE920 feed vaccine expressing a fusion protein composed of the OmpA and FlgD antigens from Edwardsiella tarda was significantly better at protecting olive flounder (Paralichthys olivaceus) from edwardsiellosis than single antigen vaccines.

    Science.gov (United States)

    Beck, Bo Ram; Lee, Soon Ho; Kim, Daniel; Park, Ji Hye; Lee, Hyun Kyung; Kwon, San-Sung; Lee, Kwan Hee; Lee, Jae Il; Song, Seong Kyu

    2017-09-01

    Edwardsiellosis is a major fish disease that causes a significant economic damage in the aquaculture industry. Here, we assessed vaccine efficacy after feeding oral vaccines to olive flounder (Paralichthys olivaceus), either L. lactis BFE920 expressing Edwardsiella tarda outer membrane protein A (OmpA), flagellar hook protein D (FlgD), or a fusion antigen of the two. Feed vaccination was done twice with a one-week interval. Fish were fed regular feed adsorbed with the vaccines. Feed vaccination was given over the course of one week to maximize the interaction between the feed vaccines and the fish intestine. Flounder fed the vaccine containing the fusion antigen had significantly elevated levels T cell genes (CD4-1, CD4-2, and CD8α), type 1 helper T cell (Th1) subset indicator genes (T-bet and IFN-γ), and antigen-specific antibodies compared to the groups fed the single antigen-expressing vaccines. Furthermore, the superiority of the fusion vaccine was also observed in survival rates when fish were challenged with E. tarda: OmpA-FlgD-expressing vaccine (82.5% survival); FlgD-vaccine (55.0%); OmpA-vaccine (50%); WT L. lactis BFE920 (37.5%); Ctrl (10%). In addition, vaccine-fed fish exhibited increased weight gain (∼20%) and a decreased feed conversion ratio (∼20%) during the four week vaccination period. Flounder fed the FlgD-expressing vaccine, either the single or the fusion form, had significantly increased expression of TLR5M, IL-1β, and IL-12p40, suggesting that the FlgD may be a ligand of olive flounder TLR5M receptor or closely related to the TLR5M pathway. In conclusion, the present study demonstrated that olive flounder fed L. lactis BFE920 expressing a fusion antigen composed of E. tarda OmpA and FlgD showed a strong protective effect against edwardsiellosis indicating this may be developed as an E. tarda feed vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Single-Dose Universal Hepatitis A Immunization in Argentina: Low Viral Circulation and High Persistence of Protective Antibodies Up to 4 Years.

    Science.gov (United States)

    Vizzotti, C; González, J; Rearte, A; Urueña, A; Pérez Carrega, M; Calli, R; Gentile, A; Uboldi, A; Ramonet, M; Cañero-Velasco, M; Diosque, M

    2015-12-01

    Single-dose hepatitis A virus (HAV) vaccination was implemented in all Argentinean children aged 12 months in 2005. Between 2005 and 2011, a dramatic decline was observed in HAV infection rates, fulminant hepatitis, and liver transplantation. This study assessed current viral circulation and estimated protective antibody persistence 4 years after vaccination. Prevalence of prevaccination anti-HAV antibodies in 12-month-old children was evaluated as an indirect estimation of viral circulation (Group A). Seroprevalence was also measured in 5-year-old children who received 1 dose of HAV vaccine at 1 year of age (Group B). Blood samples were tested for immunoglobulin (Ig)G anti-HAV antibodies (seroprotection = ≥10 mIU/mL). All Group A-positive samples were tested for IgM anti-HAV antibodies to identify recent infections. Logistic regression analysis was done to evaluate associations between demographic and socioeconomic variables and seroprotection. Of 433 children from Group A, 29.5% (95% confidence interval [CI], 25.2-33.8) were positive for IgG anti-HAV antibodies with a geometric mean concentration (GMC) of 6.17 mIU/mL (95% CI, 5.33-7.15 mIU/mL); all IgM anti-HAV were negative. From 1139 in Group B, 93% (95% CI, 91.7-94.6) maintained seroprotection with a GMC of 97.96 mIU/mL (95% CI, 89.21-107.57 mIU/mL). Kindergarten attendance was associated with seroprotection in Group B (odds ratio [OR], 2.0; 95% CI, 1.26-3.3). In contrast, high maternal educational level was associated with a lack of seroprotection in this group (OR, .26; 95% CI, .09-.8). Single-dose, universal hepatitis A immunization in infants resulted in low HAV circulation and persistent immunologic protection up to 4 years in Argentina. Variables associated with presence or absence of seroprotection in vaccinated children could be related to differences in hygiene habits in settings with residual viral circulation. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric

  20. Travelers' Health: Vaccine Recommendations for Infants and Children

    Science.gov (United States)

    ... should be taken ≥1 week before potential exposure. YELLOW FEVER VACCINE Yellow fever, a disease transmitted by mosquitoes, is endemic ... a new recommendation that a single dose of yellow fever vaccine provides long-lasting protection and is adequate for ...

  1. A forecast of typhoid conjugate vaccine introduction and demand in typhoid endemic low- and middle-income countries to support vaccine introduction policy and decisions.

    Science.gov (United States)

    Mogasale, Vittal; Ramani, Enusa; Park, Il Yeon; Lee, Jung Seok

    2017-09-02

    A Typhoid Conjugate Vaccine (TCV) is expected to acquire WHO prequalification soon, which will pave the way for its use in many low- and middle-income countries where typhoid fever is endemic. Thus it is critical to forecast future vaccine demand to ensure supply meets demand, and to facilitate vaccine policy and introduction planning. We forecasted introduction dates for countries based on specific criteria and estimated vaccine demand by year for defined vaccination strategies in 2 scenarios: rapid vaccine introduction and slow vaccine introduction. In the rapid introduction scenario, we forecasted 17 countries and India introducing TCV in the first 5 y of the vaccine's availability while in the slow introduction scenario we forecasted 4 countries and India introducing TCV in the same time period. If the vaccine is targeting infants in high-risk populations as a routine single dose, the vaccine demand peaks around 40 million doses per year under the rapid introduction scenario. Similarly, if the vaccine is targeting infants in the general population as a routine single dose, the vaccine demand increases to 160 million doses per year under the rapid introduction scenario. The demand forecast projected here is an upper bound estimate of vaccine demand, where actual demand depends on various factors such as country priorities, actual vaccine introduction, vaccination strategies, Gavi financing, costs, and overall product profile. Considering the potential role of TCV in typhoid control globally; manufacturers, policymakers, donors and financing bodies should work together to ensure vaccine access through sufficient production capacity, early WHO prequalification of the vaccine, continued Gavi financing and supportive policy.

  2. Inactivation of 10(15) chimpanzee-infectious doses of hepatitis B virus during preparation of a heat-inactivated hepatitis B vaccine

    NARCIS (Netherlands)

    Lelie, P. N.; Reesink, H. W.; Niessen, J.; Brotman, B.; Prince, A. M.

    1987-01-01

    The safety of a plasma-derived hepatitis-B vaccine inactivated by two heating steps (90 sec at 103 degrees C followed by 10 hr pasteurization at 65 degrees C) was validated in chimpanzees; 10(3) chimpanzee-infectious doses (CID50) of hepatitis-B virus (HBV), subjected to the purification steps

  3. Universal Survival Curve and Single Fraction Equivalent Dose: Useful Tools in Understanding Potency of Ablative Radiotherapy

    International Nuclear Information System (INIS)

    Park, Clint; Papiez, Lech; Zhang Shichuan; Story, Michael; Timmerman, Robert D.

    2008-01-01

    Purpose: Overprediction of the potency and toxicity of high-dose ablative radiotherapy such as stereotactic body radiotherapy (SBRT) by the linear quadratic (LQ) model led to many clinicians' hesitating to adopt this efficacious and well-tolerated therapeutic option. The aim of this study was to offer an alternative method of analyzing the effect of SBRT by constructing a universal survival curve (USC) that provides superior approximation of the experimentally measured survival curves in the ablative, high-dose range without losing the strengths of the LQ model around the shoulder. Methods and Materials: The USC was constructed by hybridizing two classic radiobiologic models: the LQ model and the multitarget model. We have assumed that the LQ model gives a good description for conventionally fractionated radiotherapy (CFRT) for the dose to the shoulder. For ablative doses beyond the shoulder, the survival curve is better described as a straight line as predicted by the multitarget model. The USC smoothly interpolates from a parabola predicted by the LQ model to the terminal asymptote of the multitarget model in the high-dose region. From the USC, we derived two equivalence functions, the biologically effective dose and the single fraction equivalent dose for both CFRT and SBRT. Results: The validity of the USC was tested by using previously published parameters of the LQ and multitarget models for non-small-cell lung cancer cell lines. A comparison of the goodness-of-fit of the LQ and USC models was made to a high-dose survival curve of the H460 non-small-cell lung cancer cell line. Conclusion: The USC can be used to compare the dose fractionation schemes of both CFRT and SBRT. The USC provides an empirically and a clinically well-justified rationale for SBRT while preserving the strengths of the LQ model for CFRT

  4. Functional and morphological changes in pig skin after single or fractionated doses in x rays

    International Nuclear Information System (INIS)

    Young, C.M.A.; Hopewell, J.W.

    1982-01-01

    The flank skin of pigs has been treated with either single or fractionated doses of x-irradiation. A single dose (2070 cGy) was compared with treatment given as 6 fractions in 18 days (6f/18 days; 3780 cGy) or 30 fractions in 39 days (30f/39 days; 8000 cGy). The doses were selected on the basis that similar levels of late tissue damage would result. Radiation induced changes in the skin were assessed by observing the skin reactions and by the measurement of isotope clearance (functional study), relative field contraction, dermal and epidermal thickness and dermal vascular density (morphological studies). In the three treatment groups the early radiation reaction varied considerably. In the first wave reaction (3 to 6 weeks after treatment) bright red erythema was recorded in many fields but moist desquamation developed only in the 30f/39 days treatment group. The second wave (10-16 weeks) was characterized by an ischemic mauve/dusky reaction. Dermal necrosis developed in 50% of the single dose fields. In the 30f/39 days regimen persistent moist desquamation progressed to dermal necrosis. Neither desquamation nor necrosis developed after 6f/18 days. Different levels of vascular damage in the dermis were assessed using an isotope clearance technique; for example in the early reaction significant changes were recorded in the papillary dermis (faster clearance) prior to the development of moist desquamation (30f/39 days) and in the reticular dermis (slower clearance) before necrosis (single dose). Changes in clearance rates have been correlated with changes in the vascular density and thickness of the dermis. Between 26 and 52 weeks (the late reaction) relative field contraction was slightly greater in the 30f/39 days group than in the other treatment groups

  5. Humoral immune responses to a single allele PfAMA1 vaccine in healthy malaria-naïve adults.

    Directory of Open Access Journals (Sweden)

    Edmond J Remarque

    Full Text Available Plasmodium falciparum: apical membrane antigen 1 (AMA1 is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. The polymorphic nature of AMA1 may compromise vaccine induced protection. The humoral response induced by two dosages (10 and 50 µg of a single allele AMA1 antigen (FVO formulated with Alhydrogel, Montanide ISA 720 or AS02 was investigated in 47 malaria-naïve adult volunteers. Volunteers were vaccinated 3 times at 4 weekly intervals and serum samples obtained four weeks after the third immunization were analysed for (i Antibody responses to various allelic variants, (ii Domain specificity, (iii Avidity, (iv IgG subclass levels, by ELISA and (v functionality of antibody responses by Growth Inhibition Assay (GIA. About half of the antibodies induced by vaccination cross reacted with heterologous AMA1 alleles. The choice of adjuvant determined the magnitude of the antibody response, but had only a marginal influence on specificity, avidity, domain recognition or subclass responses. The highest antibody responses were observed for AMA1 formulated with AS02. The Growth Inhibition Assay activity of the antibodies was proportional to the amount of antigen specific IgG and the functional capacity of the antibodies was similar for heterologous AMA1-expressing laboratory strains.ClinicalTrials.gov NCT00730782.

  6. Development of a synthetic single crystal diamond dosimeter for dose measurement of clinical proton beams

    Science.gov (United States)

    Moignier, Cyril; Tromson, Dominique; de Marzi, Ludovic; Marsolat, Fanny; García Hernández, Juan Carlos; Agelou, Mathieu; Pomorski, Michal; Woo, Romuald; Bourbotte, Jean-Michel; Moignau, Fabien; Lazaro, Delphine; Mazal, Alejandro

    2017-07-01

    The scope of this work was to develop a synthetic single crystal diamond dosimeter (SCDD-Pro) for accurate relative dose measurements of clinical proton beams in water. Monte Carlo simulations were carried out based on the MCNPX code in order to investigate and reduce the dose curve perturbation caused by the SCDD-Pro. In particular, various diamond thicknesses were simulated to evaluate the influence of the active volume thickness (e AV) as well as the influence of the addition of a front silver resin (250 µm in thickness in front of the diamond crystal) on depth-dose curves. The simulations indicated that the diamond crystal alone, with a small e AV of just 5 µm, already affects the dose at Bragg peak position (Bragg peak dose) by more than 2% with respect to the Bragg peak dose deposited in water. The optimal design that resulted from the Monte Carlo simulations consists of a diamond crystal of 1 mm in width and 150 µm in thickness with the front silver resin, enclosed by a water-equivalent packaging. This design leads to a deviation between the Bragg peak dose from the full detector modeling and the Bragg peak dose deposited in water of less than 1.2%. Based on those optimizations, an SCDD-Pro prototype was built and evaluated in broad passive scattering proton beams. The experimental evaluation led to probed SCDD-Pro repeatability, dose rate dependence and linearity, that were better than 0.2%, 0.4% (in the 1.0-5.5 Gy min-1 range) and 0.4% (for dose higher than 0.05 Gy), respectively. The depth-dose curves in the 90-160 MeV energy range, measured with the SCDD-Pro without applying any correction, were in good agreement with those measured using a commercial IBA PPC05 plane-parallel ionization chamber, differing by less than 1.6%. The experimental results confirmed that this SCDD-Pro is suitable for measurements with standard electrometers and that the depth-dose curve perturbation is negligible, with no energy dependence and no significant dose rate

  7. Controlled single-blind clinical evaluation of low-dose mammographic screen: film systems

    International Nuclear Information System (INIS)

    Sickles, E.A.; Genant, H.K.

    1979-01-01

    The ability of five low-dose mammographic screen-film systems to portray normal and abnormal breast structures was evaluated in parallel with a study of physical image properties. Single-blind evaluations of the visibility of normal breast architecture, mass lesions, and calcifications were made on the mammograms of 100 patients radiographed with each of the systems. There was increased noise and slightly poorer resolution of the faster recording systems, but there was no difference in final diagnostic impressions among the five systems. These results suggest that the faster systems will result in substantial dose reduction without sacrificing diagnostic accuracy

  8. Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS)

    DEFF Research Database (Denmark)

    Pauls, Mathilde M H; Clarke, Natasha; Trippier, Sarah

    2017-01-01

    vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. METHODS/DESIGN: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double......-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. SAMPLE SIZE: 54 participants are required to detect a 15% increase in cerebral blood...

  9. Pharmacokinetics of colistin methanesulfonate (CMS) in healthy Chinese subjects after single and multiple intravenous doses.

    Science.gov (United States)

    Zhao, Miao; Wu, Xiao-Jie; Fan, Ya-Xin; Zhang, Ying-Yuan; Guo, Bei-Ning; Yu, Ji-Cheng; Cao, Guo-Ying; Chen, Yuan-Cheng; Wu, Ju-Fang; Shi, Yao-Guo; Li, Jian; Zhang, Jing

    2018-05-01

    The high prevalence of extensively drug-resistant Gram-negative pathogens has forced clinicians to use colistin as a last-line therapy. Knowledge on the pharmacokinetics of colistin methanesulfonate (CMS), an inactive prodrug, and colistin has increased substantially; however, the pharmacokinetics in the Chinese population is still unknown due to lack of a CMS product in China. This study aimed to evaluate the pharmacokinetics of a new CMS product developed in China in order to optimise dosing regimens. A total of 24 healthy subjects (12 female, 12 male) were enrolled in single- and multiple-dose pharmacokinetic (PK) studies. Concentrations of CMS and formed colistin in plasma and urine were measured, and PK analysis was conducted using a non-compartmental approach. Following a single CMS dose [2.36 mg colistin base activity (CBA) per kg, 1 h infusion], peak concentrations (C max ) of CMS and formed colistin were 18.0 mg/L and 0.661 mg/L, respectively. The estimated half-life (t 1/2 ) of CMS and colistin were 1.38 h and 4.49 h, respectively. Approximately 62.5% of the CMS dose was excreted via urine within 24 h after dosing, whilst only 1.28% was present in the form of colistin. Following multiple CMS doses, colistin reached steady-state within 24 h; there was no accumulation of CMS, but colistin accumulated slightly (R AUC  = 1.33). This study provides the first PK data in the Chinese population and is essential for designing CMS dosing regimens for use in Chinese hospitals. The urinary PK data strongly support the use of intravenous CMS for serious urinary tract infections. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  10. Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

    Science.gov (United States)

    Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

    2017-06-01

    The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. TUMOUR VACCINE

    NARCIS (Netherlands)

    Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert

    1999-01-01

    The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a

  12. Sources of variability in OSL dose measurements using single grains of quartz

    International Nuclear Information System (INIS)

    Thomsen, K.J.; Murray, A.S.; Boetter-Jensen, L.

    2005-01-01

    In luminescence-based measurements of dose distributions in unheated mineral samples, the observed spread in dose values is usually attributed to four main factors: fluctuations in the number of photons counted, incomplete zeroing of any prior trapped charge (including signals arising from thermal transfer), heterogeneity in dosimetry, and instrument reproducibility. For correct interpretation of measured dose distributions in retrospective dosimetry, it is important to understand the relative importance of these components, and to establish whether other factors also contribute to the observed spread. In this preliminary study, dose distributions have been studied using single grains of heated and laboratory irradiated quartz. By heating the sample, the contribution from incomplete zeroing was excluded and at the same time the sample was sensitised. The laboratory gamma irradiation was designed to deliver a uniform dose to the sample. Thus it was anticipated that statistical fluctuations in the number of photons counted and instrument reproducibility, both quantifiable entities, should be able to account for all the observed variance in the measured dose distributions. We examine this assumption in detail, and discuss the origins and importance of the residual variance in our data

  13. Mechanism of action for anti-radiation vaccine in reducing the biological impact of high-dose gamma irradiation

    Science.gov (United States)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after high-dose gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naïve animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which they mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  14. Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study.

    Science.gov (United States)

    Heppner, D Gray; Kemp, Tracy L; Martin, Brian K; Ramsey, William J; Nichols, Richard; Dasen, Emily J; Link, Charles J; Das, Rituparna; Xu, Zhi Jin; Sheldon, Eric A; Nowak, Teresa A; Monath, Thomas P

    2017-08-01

    The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log 10 dose range in two sequential cohorts. In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18-61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 10 3 , 3 × 10 4 , 3 × 10 5 , or 3 × 10 6 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 10 6 , 9 × 10 6 , 2 × 10 7 , or 1 × 10 8 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov, number NCT02314923. Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 10 3 [n=64], 3 × 10 4 [n=64], 3 × 10 5 [n=64], or 3 × 10 6 PFU [n=64]) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 10 6 [n=20], 9 × 10 6 [n=47], 2 × 10 7 [n=47], or 1 × 10 8 PFU [n=48]) and 20 received placebo. Most

  15. Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults.

    Science.gov (United States)

    Barden, Jodie; Derry, Sheena; McQuay, Henry J; Moore, R Andrew

    2009-10-07

    Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis.Ketoprofen at doses between 12.5 mg and 100 mg produced NNTs for at least 50% pain relief over 4 to 6

  16. Impact of multiple-dose versus single-dose inhaler devices on COPD patients’ persistence with long-acting β2-agonists: a dispensing database analysis

    Science.gov (United States)

    van Boven, Job FM; van Raaij, Joost J; van der Galiën, Ruben; Postma, Maarten J; van der Molen, Thys; Dekhuijzen, PN Richard; Vegter, Stefan

    2014-01-01

    Background: With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients’ persistence with long-acting β2-agonists (LABAs). Aims: To assess the impact of the type of inhaler device (multiple-dose versus single-dose inhalers) on 1-year persistence and switching patterns with LABAs. Methods: A retrospective observational cohort study was performed comparing a cohort of patients initiating multiple-dose inhalers and a cohort initiating single-dose inhalers. The study population consisted of long-acting bronchodilator naive COPD patients, initiating inhalation therapy with mono-LABAs (formoterol, indacaterol or salmeterol). Analyses were performed using pharmacy dispensing data from 1994 to 2012, obtained from the IADB.nl database. Study outcomes were 1-year persistence and switching patterns. Results were adjusted for initial prescriber, initial medication, dosing regimen and relevant comorbidities. Results: In all, 575 patients initiating LABAs were included in the final study cohort. Among them, 475 (83%) initiated a multiple-dose inhaler and 100 (17%) a single-dose inhaler. Further, 269 (47%) initiated formoterol, 9 (2%) indacaterol and 297 (52%) salmeterol. There was no significant difference in persistence between users of multiple-dose or single-dose inhalers (hazard ratio: 0.98, 95% confidence interval: 0.76–1.26, P=0.99). Over 80% re-started or switched medication. Conclusions: There seems no impact of inhaler device (multiple-dose versus single-dose inhalers) on COPD patients’ persistence with LABAs. Over 80% of patients who initially seemed to discontinue LABAs, re-started their initial medication or switched inhalers or medication within 1 year. PMID:25274453

  17. Single high dose intraoperative electrons for advanced stage pancreatic cancer: Phase I pilot study

    International Nuclear Information System (INIS)

    Goldson, A.L.; Ashaveri, E.; Espinoza, M.C.

    1981-01-01

    Phase I toxicity studies with intraoperative radiotherapy proved to be a feasible adjunct to surgery for unresectable malignancies of the pancreas at Howard University Hospital. There have been minimal side effects or complications related to the combination of limited surgical decompression and intraoperative radiotherapy alone. The toxic effects of intraoperative radiotherapy on normal tissues is being assessed on a dose volume basis. Doses of 2000 to 2500 rad in a single exposure to include the pancreas, regional nodes and duodenum are acceptable if the total treatment volume is less than or equal to 100 cm. The tumoricidal effects on the cancer are demonstratable when one reviews the pathological specimens that illustrate massive tumor necrosis and fibros replacement, but in all cases reviewed, viable cancer was noted. Intraoperative radiotherapy, therefore, represents a significant boost dose for resectable, partially resectable or non-resectable tumors when added to conventional external beam irradiation and/or chemotherapy. Preliminary clinical data and minimal toxicity justifies further investigation

  18. Serum tocopherol levels in very preterm infants after a single dose of vitamin E at birth.

    Science.gov (United States)

    Bell, Edward F; Hansen, Nellie I; Brion, Luc P; Ehrenkranz, Richard A; Kennedy, Kathleen A; Walsh, Michele C; Shankaran, Seetha; Acarregui, Michael J; Johnson, Karen J; Hale, Ellen C; Messina, Lynn A; Crawford, Margaret M; Laptook, Abbot R; Goldberg, Ronald N; Van Meurs, Krisa P; Carlo, Waldemar A; Poindexter, Brenda B; Faix, Roger G; Carlton, David P; Watterberg, Kristi L; Ellsbury, Dan L; Das, Abhik; Higgins, Rosemary D

    2013-12-01

    Our aim was to examine the impact of a single enteral dose of vitamin E on serum tocopherol levels. The study was undertaken to see whether a single dose of vitamin E soon after birth can rapidly increase the low α-tocopherol levels seen in very preterm infants. If so, this intervention could be tested as a means of reducing the risk of intracranial hemorrhage. Ninety-three infants vitamin E or placebo by gastric tube within 4 hours of birth. The vitamin E group received 50 IU/kg of vitamin E as dl-α-tocopheryl acetate (Aquasol E). The placebo group received sterile water. Blood samples were taken for measurement of serum tocopherol levels by high-performance liquid chromatography before dosing and 24 hours and 7 days after dosing. Eighty-eight infants received the study drug and were included in the analyses. The α-tocopherol levels were similar between the groups at baseline but higher in the vitamin E group at 24 hours (median 0.63 mg/dL vs. 0.42 mg/dL, P = .003) and 7 days (2.21 mg/dL vs 1.86 mg/dL, P = .04). There were no differences between groups in γ-tocopherol levels. At 24 hours, 30% of vitamin E infants and 62% of placebo infants had α-tocopherol levels vitamin E raised serum α-tocopherol levels, but to consistently achieve α-tocopherol levels >0.5 mg/dL, a higher dose or several doses of vitamin E may be needed.

  19. Pharmacokinetics of diclofenac in pigs after intramuscular administration of a single dose

    OpenAIRE

    Pejčić Zorica; Pokrajac Milena; Jezdimirović Milanka

    2006-01-01

    The pharmacokinetics of diclofenac was studied in 10 clinically normal male Yorkshire pigs, following intramuscular (i.m) administration of a single dose of diclofenac-sodium (2.5 mg/kg body weight). Diclofenac serum concentrations were determined by high pressure- liquid-chromatography (HPLC), with UV detection (226 nm). Following i.m. administration all individual diclofenac serum levels best fitted the one-compartment open model for extravascular administration. The maximal diclofenac seru...

  20. Effect of a Single Dose of Dextromethorphan on Psychomotor Performance and Working Memory Capacity

    OpenAIRE

    Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.; Ashor, Ammar Waham

    2012-01-01

    Background: Previous studies show that the prolonged use of dextromethorphan produces cognitive deterioration in humans. Aim: The aim of this study was to investigate the effect of a single dose of dextroemthrophan on psychomotor performance and working memory capacity. Materials and Methods: This is a randomized, double-blind, controlled, and prospective study. Thirty-six (17 women, 19 men) medical students enrolled in the study; half of them (7 women, 11 men) were given placebo, while the o...

  1. Lack of protective effect of thromboxane synthetase inhibitor (CGS-13080) on single dose radiated canine intestine

    International Nuclear Information System (INIS)

    Barter, J.F.; Marlow, D.; Kamath, R.K.; Harbert, J.; Torrisi, J.R.; Barnes, W.A.; Potkul, R.K.; Newsome, J.T.; Delgado, G.

    1991-01-01

    The effect of a thromboxane A2 synthetase inhibitor (CGS-13080) on canine intestine was studied using a single dose of radiation, and radioactive microspheres were used to determine resultant blood flow. Thromboxane A2 causes vasospasm and platelet aggregation and may play a dominant role in radiation injury. However, there was no effect on the intestinal blood flow diminution occurring after radiation in this laboratory model using this thromboxane A2 synthetase inhibitor

  2. Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

    2013-06-01

    To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

  3. Mouse single oral dose toxicity test of bupleuri radix aqueous extracts.

    Science.gov (United States)

    Kim, Kyung-Hu; Gam, Cheol-Ou; Choi, Seong-Hun; Ku, Sae-Kwang

    2012-03-01

    The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, LD50 (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

  4. Effect of an Early Dose of Measles Vaccine on Morbidity Between 18 Weeks and 9 Months of Age: A Randomized, Controlled Trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Do, Vu An; Biering-Sorensen, Sofie; Fisker, Ane Bærent

    2017-01-01

    with a higher risk of the well-known adverse events of fever, rash, and convulsions within the first 14 days. From 15 days after randomization to age 9 months, early measles vaccination was associated with reductions in maternally reported diarrhea (hazard ratio [HR], 0.89; 95% confidence interval [CI],.82-. 97......Background: Children in Guinea-Bissau receive measles vaccine (MV) at 9 months of age, but studies have shown that an additional dose before 9 months of age might have beneficial nonspecific effects. Within a randomized trial designed to examine nonspecific effects of early MV receipt on mortality......, we conducted a substudy to investigate the effect of early MV receipt on morbidity. Methods: Children were randomly assigned at a ratio of 2: 1 to receive 2 doses of MVat 18 weeks and age 9 months (intervention group) or 1 dose of MV at age 9 months, in accordance with current practice (control group...

  5. Concentrations of amoxicillin and clindamycin in teeth following a single dose of oral medication.

    Science.gov (United States)

    Schüssl, Yvonne; Pelz, Klaus; Kempf, Jürgen; Otten, Jörg-Elard

    2014-01-01

    The main purpose of this study is the detection of amoxicillin and clindamycin concentrations in teeth. Eleven patients received 2 g of amoxicillin, and 11 patients received 600 mg of clindamycin in a single dose of oral medication at least 60 min prior to tooth extraction due to systemic diseases. The concentrations were determined in crowns and roots separately using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Amoxicillin (13 samples) and clindamycin (12 samples) were detected in the samples of the root and crown preparations of the extracted teeth. The mean concentration of amoxicillin was 0.502 μg/g in the roots and 0.171 μg/g in the crowns. The mean concentration of clindamycin was 0.270 μg/g in the roots and 0.064 μg/g in the crowns. A single dose of oral amoxicillin and clindamycin leads to concentrations of both antibiotics in teeth which exceed the minimal inhibition concentration of some oral bacteria. The proof of antibacterial activity in dental hard tissue after oral single-dose application is new. The antimicrobial effect of amoxicillin and clindamycin concentrations in roots of teeth may be of clinical relevance to bacterial reinfection from dentinal tubules.

  6. Fluralaner as a single dose oral treatment for Caparinia tripilis in a pygmy African hedgehog.

    Science.gov (United States)

    Romero, Camilo; Sheinberg Waisburd, Galia; Pineda, Jocelyn; Heredia, Rafael; Yarto, Enrique; Cordero, Alberto M

    2017-12-01

    African pygmy hedgehogs (Atelerix albiventris) are popular pets belonging to the Erinaceidae family of spined mammals. Amongst the most common skin diseases occurring in this species is infestation caused by the mite Caparinia spp. Due to their skin anatomy and spiny coat, detection of skin lesions in these hedgehogs can be difficult. This may result in delays in seeking medical care, which may lead to secondary bacterial infection and self-inflicted trauma. Multiple therapies have been used in the treatment of this skin condition including ivermectin, amitraz, fipronil and selamectin. A drug which could be administered as a single oral dose would be advantageous to these pets and their owners. To evaluate the effect of a single oral dose (15 mg/kg) of fluralaner on Caparinia tripilis infestation in the African pygmy hedgehog. A 10-month-old African pygmy hedgehog weighing 184 g. Response to treatment was monitored by dermatological examination and superficial skin scrapings repeated at 7, 14, 21, 30, 60, 90 and 120 days following fluralaner administration. On Day 7 after treatment, adult mites were observed exhibiting normal movement. On Day 14, only dead mites were observed. No life stages of the mites were found after Day 21. A single oral dose at 15 mg/kg of fluralaner was effective within 21 days after treatment for capariniasis in this case. Further studies are required to evaluate the drug's safety and toxicology in hedgehogs, and to confirm efficacy. © 2017 ESVD and ACVD.

  7. Radiation hardening at 77 K in Zn and Cu single crystals at low doses

    International Nuclear Information System (INIS)

    Gonzalez, H.C.; Bisogni, E.A.

    1980-01-01

    There is controversy about radiation hardening phenomenon and its additivity with other hardening mechanisms. The purpose of this work is to contribute to the understanding of this subject, through measurements made in Zn and Cu single crystals. Post-irradiation measurements of yield stress of Zn, made on different single crystals, show a direct proportionality to the 0.5 power of the dose. It is determined that for a dose greater than 3.7 x 10 16 neutrons cm -2 s -1 there is always cleavage. The maximum critical resolved shear stress measured is about 8.82 MPa. In order to study additivity it is necessary to lower experimental errors. A micro tensile machine is designed to operate in the CNEA facility RA1 in a bath of liquid N 2 . Experimental measurements of yield stress with dose are carried out in-situ on the same single crystals. Experimental results on Cu and Zn show that radiation induced yield stress increases with a 0.5 power law. It must be taken into account that the definition of radiation induced yield stress stands for radiation created obstacles operating alone. The radiation induced yield stress adds algebraically to the athermal component of the initial yield stress but is not exactly additive to the other thermally activated mechanisms. A gradual transition from one to the other type of obstacles is observed. (author)

  8. A single dose of dark chocolate increases parasympathetic modulation and heart rate variability in healthy subjects

    Directory of Open Access Journals (Sweden)

    Ana Amélia Machado DUARTE

    Full Text Available ABSTRACT Objective: The aim of this study was to investigate the acute effect of a single dose of dark chocolate (70% cocoa on blood pressure and heart rate variability. Methods: Thirty-one healthy subjects (aged 18-25 years; both sexes were divided into two groups: 10 subjects in the white chocolate (7.4 g group and 21 in the dark chocolate (10 g group; measurements were performed at the university's physiology lab. An electrocardiogram measured the sympathovagal balance by spectral and symbolic analysis. Results: A single dose of dark chocolate significantly reduced systolic blood pressure and heart rate. After consuming 10 g of dark chocolate, significant increases were observed for heart rate variability, standard deviation of RR intervals standard deviation of all NN intervals, square root of the mean squared differences between adjacent normal RR intervals root mean square of successive differences, and an increase in the high frequency component in absolute values, representing the parasympathetic modulation. Conclusion: In conclusion the importance of our results lies in the magnitude of the response provoked by a single dose of cocoa. Just 10 g of cocoa triggered a significant increase in parasympathetic modulation and heart rate variability. These combined effects can potentially increase life expectancy because a reduction in heart rate variability is associated with several cardiovascular diseases and higher mortality.

  9. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

    Science.gov (United States)

    Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

    2015-06-25

    Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

  10. Frequency of wound infection in non-perforated appendicitis with use of single dose perforative antibiotics

    International Nuclear Information System (INIS)

    Ali, K.; Latif, H.; Ahmad, S.

    2015-01-01

    Antibiotics are used both pre and post-operatively in acute appendicitis for preventing wound infection. It has been observed that the routine use of post-operative antibiotics is not necessary in cases of non-perforated appendicitis as only prophylactic antibiotics are sufficient to prevent wound infection. The aim of this study was to see the frequency of wound infection in non-perforated appendicitis with single dose preoperative antibiotics only. Method: This observational study was conducted at the Department of Surgery, Ayub Medical College, Abbottabad from May to November 2014. A total of 121 patients with non-perforated appendicitis were included in the study. Only single dose preoperative antibiotics were used. The patients were followed for wound infection till 8th post-operative day. Results: 121 patients, 56(46.28%) male and 65(53.72%) female were included in the study. The mean age of patients was 27.41 ± 7.12 years with an age range of 18 to 45 years. In the entire series, 7(5.78%) patients developed wound infection. The infection was minor which settled with conservative therapy. Prophylactic antibiotics were found efficacious in 114(94.21%) patients. There was no significant association between wound infection and age and gender. Conclusion: Single dose preoperative antibiotics were found effective in controlling post-operative wound infection without the need of extending the antibiotics to post-operative period in cases of non-perforated appendicitis. (author)

  11. Optimizing a single fixed dose of Iodine-131 in Graves' Disease (An Experience)

    International Nuclear Information System (INIS)

    Khan, S.H.

    2007-01-01

    Full text: Kashmir is a Himalayan mountain state of India enclosed by high snow capped ridges of Pir Panjal Mountains at an average height of 4000-5000 meters above the sea level. For most of the 4 million inhabitants in this land locked valley, agriculture horticulture and handcrafts are the main source of income. Due to long and severe winters the terraced farming on the mountain slopes yield just a single crop of rice which is barely sufficient to meet the local needs of this staple diet. People are relatively poor with low annual per capita income. Goiter is endemic in the Valley of Kashmir. In a published report the overall prevalence of goiter among the school going children in Kashmir between the ages of 5 years is 45.2% (+ SEM) with urinary iodine excretion of 49 + 3.55 μg per gram of creatinine. The extremely shy people of Kashmir are casual towards the aesthetic aspects of their goiters but nevertheless seek medical advice when associated with physical symptoms. In a published study of 203 patients of thyrotoxicosis from Kashmir, Graves' disease was the commonest cause, accounting for 63% of patients. One hundred and twentyone patients of Graves' disease were prospectively studied for their response to a single fixed dose of I-131. Patients were randomly treated with two different fixed doses of I- 131. Sixty four patients belonging to Group-I received a fixed dose of 185 MBq (Low Dose) and 57 patients belonging to Group -2 received 370 MBq (High Dose) of I- 131. Following therapy all patients were evaluated at 3 months. Patients with normal or reduced thyroid hormone levels were termed as responders and those with persistently elevated levels of thyroid hormone were termed as non responders. The response rates among the two groups were analyzed for their statistical significance. Patients treated with the high fixed dose of 370 MBq revealed good response to therapy achieving a rate of 91.22%, while the response rate in the group of patients treated with

  12. Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2

    DEFF Research Database (Denmark)

    Bjoern, J; Brimnes, M K; Andersen, M H

    2011-01-01

    In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-α and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high......) , was prospectively analysed in fresh blood, and treatment-associated quantitative and qualitative changes were analysed. By the 4th vaccine, patients showed a marked increase in CD4+ CD25(high) T cell subset from 6% to 22% (P...

  13. Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2

    DEFF Research Database (Denmark)

    Bjoern, J; Brimnes, M K; Andersen, M H

    2011-01-01

    In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-a and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high......) , was prospectively analysed in fresh blood, and treatment-associated quantitative and qualitative changes were analysed. By the 4th vaccine, patients showed a marked increase in CD4+ CD25(high) T cell subset from 6% to 22% (P...

  14. Feasibility of optimizing the dose distribution in lung tumors using fluorine-18-fluorodeoxyglucose positron emission tomography and single photon emission computed tomography guided dose prescriptions

    International Nuclear Information System (INIS)

    Das, S.K.; Miften, M.M.; Zhou, S.; Bell, M.; Munley, M.T.; Whiddon, C.S.; Craciunescu, O.; Baydush, A.H.; Wong, T.; Rosenman, J.G.; Dewhirst, M.W.; Marks, L.B.

    2004-01-01

    The information provided by functional images may be used to guide radiotherapy planning by identifying regions that require higher radiation dose. In this work we investigate the dosimetric feasibility of delivering dose to lung tumors in proportion to the fluorine-18-fluorodeoxyglucose activity distribution from positron emission tomography (FDG-PET). The rationale for delivering dose in proportion to the tumor FDG-PET activity distribution is based on studies showing that FDG uptake is correlated to tumor cell proliferation rate, which is shown to imply that this dose delivery strategy is theoretically capable of providing the same duration of local control at all voxels in tumor. Target dose delivery was constrained by single photon emission computed tomography (SPECT) maps of normal lung perfusion, which restricted irradiation of highly perfused lung and imposed dose-function constraints. Dose-volume constraints were imposed on all other critical structures. All dose-volume/function constraints were considered to be soft, i.e., critical structure doses corresponding to volume/function constraint levels were minimized while satisfying the target prescription, thus permitting critical structure doses to minimally exceed dose constraint levels. An intensity modulation optimization methodology was developed to deliver this radiation, and applied to two lung cancer patients. Dosimetric feasibility was assessed by comparing spatially normalized dose-volume histograms from the nonuniform dose prescription (FDG-PET proportional) to those from a uniform dose prescription with equivalent tumor integral dose. In both patients, the optimization was capable of delivering the nonuniform target prescription with the same ease as the uniform target prescription, despite SPECT restrictions that effectively diverted dose from high to low perfused normal lung. In one patient, both prescriptions incurred similar critical structure dosages, below dose-volume/function limits

  15. Single-fraction stereotactic radiotherapy: a dose-response analysis of arteriovenous malformation obliteration

    International Nuclear Information System (INIS)

    Touboul, Emmanuel; Al Halabi, Assem; Buffat, Laurent; Merienne, Louis; Huart, Judith; Schlienger, Michel; Lefkopoulos, Dimitrios; Mammar, Hamid; Missir, Odile; Meder, Jean-Francois; Laurent, Alex; Housset, Martin

    1998-01-01

    Purpose: Stereotactic radiotherapy delivered in a high-dose single fraction is an effective technique to obliterate intracranial arteriovenous malformations (AVM). To attempt to analyze the relationships between dose, volume, and obliteration rates, we studied a group of patients treated using single-isocenter treatment plans. Methods and Materials: From May 1986 to December 1989, 100 consecutive patients with angiographically proven AVM had stereotactic radiotherapy delivered as a high-dose single fraction using a single-isocenter technique. Distribution according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0 grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in 11, and large and irregular in 15. The targeted volume of the nidus was estimated using two-dimensional stereotactic angiographic data and, calculated as an ovoid-shaped lesion, was 1900 ± 230 mm 3 (median 968 mm 3 ; range 62-11, 250 mm 3 ). The mean minimum target dose (D min ) was 19 ± 0.6 Gy (median 20 Gy; range: 3-31.5). The mean volume within the isodose which corresponded to the minimum target dose was 2500 ± 300 mm 3 (median 1200 mm 3 ; range 75-14 900 mm 3 ). The mean maximum dose (D max ) was 34.5 ± 0.5 Gy (median 35 Gy; range 15-45). The mean angiographic follow-up was 42 ± 2.3 months (median 37.5; range 7-117). Results: The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate was 62.5 ± 7%. After univariate analysis, AVM obliteration was influenced by previous surgery (p = 0.0007), D min by steps of 5 Gy (p = 0.005), targeted volume of the nidus (≤968 mm 3 vs. >968 mm 3 ; p = 0.015), and grade according to Spetzler-Martin (grade 1-3 vs. grade 4-6; p = 0.011). After multivariate analysis, the independent factors influencing AVM obliteration were the D min [relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p min but does not seem to be influenced by D max and the targeted volume of the nidus

  16. Mechanism of Action for Anti-radiation Vaccine in Reducing the Biological Impact of High-dose Gamma Irradiation

    Science.gov (United States)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    2007-01-01

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  17. Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

    Science.gov (United States)

    Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

    2011-05-01

    The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

  18. Dengue vaccines: Are they safe for travelers?

    Science.gov (United States)

    Halstead, Scott B; Aguiar, Maira

    2016-01-01

    The four dengue viruses (DENV) circulate among nearly one-half of the world's population in tropical and semitropical countries imposing a huge morbidity burden on travelers. Sanofipasteur has developed a tetravalent live-attenuated vaccine, Dengvaxia, recently approved by the World Health Organization and licensed in four dengue-endemic countries. An additional two dengue vaccines, developed by the National Institute of Allergy and Infectious Diseases (NIAID), USA and Takeda, are entering phase III testing. Dengvaxia is composed of four yellow fever 17D-DENV chimeras, the NIAID vaccine contains three mutagenized DENV and one DENV2/4 chimera while the Takeda vaccine contains an attenuated DENV 2 and three DENV 2-DENV chimeras. Which of these vaccines might be useful in protecting travelers against dengue infections and disease? Dengvaxia requires three doses administered over the course of one year but in addition has safety signals suggesting that susceptible individuals should not be vaccinated. The NIAID vaccine is promising as a travel vaccine as a single dose fully protected susceptible adults against live dengue 2 virus challenge. The protective efficacy and safety of the Takeda vaccine remain to be demonstrated. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

    International Nuclear Information System (INIS)

    Leith, J.T.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Howard, J.

    1982-01-01

    The thoraco-lumbar (T12-L1) region of the spinal cord of rats was exposed to either single or fractionated (four daily exposures) doses of X rays (230 kVp) or heavy ions. The heavy ions used were carbon and neon, and the relative biological effectiveness (RBE) of both the plateau ionization region and the midpeak region of 4-cm spread-out Bragg peaks of each heavy ion were investigated. For single doses of carbon and neon ions in the plateau ionization region, RBE values of 1.45 +/- 0.25 (propagated 95% confidence limits) and 1.46 +/- 0.33, respectively, were obtained. In the spread peak regions for carbon and neon ions, the RBE values were 1.48 +/- 0.18 and 1.86 +/- 0.42, respectively. These values were obtained using the dose needed to produce 50% paralysis in a group of irradiated rats as the isoeffect comparison dose (ED 50 dose). Similarly, in groups of rats receiving four daily exposures, the RBE values for carbon and neon ions in the plateau ionization region were 1.31 +/- 0.27 and 1.80 +/- 0.24, respectively. In the spread peak regions of ionization for carbon and neon ions, the RBE values were 1.95 +/- 0.19 and 2.18 +/- 0.23, respectively. Similar values for RBE were obtained using changes in the activity of enzymes in spinal cord tissue (cyclic nucleotide phosphohydrolase and γ-glutamyl transpeptidase). Also, it was estimated that, for X irradiation, the fractional amount of dose repaired (at the ED 50 dose) was 0.64 +/- 0.10 (95% confidence limits). For carbon and neon ions in the plateau ionization region, the values for the fractional amount of dose repaired were 0.70 +/- 0.27 and 0.48 +/- 0.20, and for carbon and neon ions in the spread peak region of ionization, the fractional repair values were 0.40 +/- 0.10 and 0.52 +/- 0.17. Spinal cord tissue therefore shows a high capacity for subeffective damage repair

  20. Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine.

    Science.gov (United States)

    Danchin, M; Kirkwood, C D; Lee, K J; Bishop, R F; Watts, E; Justice, F A; Clifford, V; Cowley, D; Buttery, J P; Bines, J E

    2013-05-28

    RV3 is a human neonatal rotavirus strain (G3P[6]) that has been associated with asymptomatic neonatal infection and replicates well in the infant gut. RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth. A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3×10(6)FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort). Vaccine take was defined as seroconversion (a 3-fold increase in serum anti-rotavirus IgA or serum neutralising antibody (SNA) from baseline at day 28 post-dose) or evidence of RV3-BB viral replication in the faeces by RT-PCR analysis 3-6 days post-vaccination. RV3-BB presence was confirmed by sequence analysis. The RV3-BB vaccine was well tolerated in all participants, with no pattern of adverse events shown to be associated with the study vaccine. In the infant cohort, vaccine take was demonstrated in 8/9 infants following a single dose of vaccine compared with 2/7 placebo recipients. In the infant vaccine group, 5/9 infants exhibited either IgA or SNA seroconversion and 7/9 infants had evidence of RV3-BB replication on days 3-6, compared with 2/7 infants who seroconverted and 0/10 infants with evidence of replication in the placebo group. Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant. A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Economic evaluation of vaccination programme of mumps vaccine to the birth cohort in Japan.

    Science.gov (United States)

    Hoshi, Shu-ling; Kondo, Masahide; Okubo, Ichiro

    2014-07-16

    The most common preventative measure against mumps is vaccination with mumps vaccine. In most parts of the world, mumps vaccine is routinely delivered through live attenuated Measles-Mumps-Rubella (MMR) vaccine. In Japan, receiving mumps vaccine is voluntary and vaccine uptake rate is less than 30%. The introduction of mumps vaccine into routine vaccination schedule has become one of the current topics in health policy and has raised the need to evaluate efficient ways in protecting children from mumps-related diseases in Japan. We conducted a cost-effectiveness analysis with Markov model and calculated incremental cost effectiveness ratios (ICERs) of 11 different programmes; a single-dose programme at 12-16 months and 10 two-dose programmes with second dose uptakes at ages 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11. Our base-case analyse set the cost per shot at ¥6951 (US$72; 1US$=96.8). Results show that single-dose programme dominates status quo. On the other hand, ICERs of all 10 two-dose programmes are under ¥6,300,000 (US$65,082) per QALY from payer's perspective while it ranged from cost-saving to <¥7,000,000 (US$72,314) per QALY from societal perspective. By adopting WHO's classification that an intervention is cost-effective if ICER (in QALY) is between one and three times of GDP as a criterion, either of the vaccination programme is concluded as cost-effective from payer's or societal perspectives. Likewise, to uptake second dose at 3-5 years old is more favourable than an uptake at any other age because of lower incremental cost-effectiveness ratios. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Treatment of chronic spontaneous urticaria with a single dose of omalizumab: A study of four cases

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Subramaniyan

    2016-01-01

    Full Text Available Background: Chronic spontaneous urticaria (CSU has a detrimental effect on patients′ emotional and physical quality of life. Omalizumab, an anti-immunoglobulin E humanized monoclonal antibody, has been shown to be very effective in the treatment of refractory chronic urticaria patients but may not be an economically viable option for all CSU patients. However, we present a case series where a single dose of omalizumab gave sustained relief of symptoms in patients with CSU, which may be an economical option. Aims: The aim of this study is to assess the efficacy of a single dose of omalizumab in the treatment of CSU. Materials and Methods: Four patients of CSU whose disease was not controlled with four times the licensed dose of tablet fexofenadine 180 mg were exhibited one subcutaneous injection of omalizumab and were followed up at 4 weekly intervals for 24 weeks for Weekly Urticaria Activity Score 7 (UAS7 and Dermatology Life Quality Index (DLQI. Results: A sharp decline in UAS7 and DLQI was documented in 7-10 days. The decline was maintained up to 16 weeks in one case and 20 weeks in the other three cases. Both the scores at the end of the follow-up period of 24 weeks were better than the pre-omalizumab scores. Conclusion: The results of this case series indicate the efficacy of a single-dose omalizumab in treating moderate to severe refractory CSU. Further studies are required to identify the minimum frequency of administering omalizumab to effectively control CSU. This would greatly reduce the cost of this novel therapy.

  3. Radiotherapy for calcaneodynia. Results of a single center prospective randomized dose optimization trial

    Energy Technology Data Exchange (ETDEWEB)

    Ott, O.J.; Jeremias, C.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R. [University Hospital Erlangen (Germany). Dept. of Radiation Oncology

    2013-04-15

    The aim of this work was to compare the efficacy of two different dose fractionation schedules for radiotherapy of patients with calcaneodynia. Between February 2006 and April 2010, 457 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy using the orthovoltage technique. One radiotherapy series consisted of 6 single fractions/3 weeks. In case of insufficient remission of pain after 6 weeks a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before, immediately after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). The overall response rate for all patients was 87 % directly after and 88 % 6 weeks after radiotherapy. The mean VAS values before, immediately after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 65.5 {+-} 22.1 and 64.0 {+-} 20.5 (p = 0.188), 34.8 {+-} 24.7 and 39.0 {+-} 26.3 (p = 0.122), and 25.1 {+-} 26.8 and 28.9 {+-} 26.8 (p = 0.156), respectively. The mean CPS before, immediately after, and 6 weeks after treatment was 10.1 {+-} 2.7 and 10.0 {+-} 3.0 (p = 0.783), 5.6 {+-} 3.7 and 6.0 {+-} 3.9 (p = 0.336), 4.0 {+-} 4.1 and 4.3 {+-} 3.6 (p = 0.257), respectively. No statistically significant differences between the two single dose trial arms for early (p = 0.216) and delayed response (p = 0.080) were found. Radiotherapy is an effective treatment option for the management of calcaneodynia. For radiation protection reasons, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy. (orig.)

  4. Orientation of streptococcus agalactiae irradiation dose for subclinical mastitis vaccine in dairy cows

    International Nuclear Information System (INIS)

    Tuasikal, B.J.; Estuningsih, S.; Pasaribu, F.H.; Wibawan, I.W.T.

    2012-01-01

    An experiment to determine the effect of gamma-ray irradiation in debilitating Streptococcus agalactiae as a cause of subclinical mastitis (inflammation of the udder) in cows has been conducted. S. agalactiae bacteria was isolated from subclinical mastitis found in dairy cows in the field was then observed for its cell growth. The bacteria which have reached mid-log phase of growth, were divided into 5 treatment groups, of which each was irradiated at dose level of 0; 25; 50; 75; and 100Gy. Irradiated bacteria subsequently were grown on Brain Heart Infusion agar (BHI), and each of its colonies was counted for LD50 determination. The obtained curves from irradiated treatment bacterial shown viability percentage by the linier equation of Y = 95.414 e -0,0371X ; R 2 = 0.9979, while Y = % viability and X = dose of irradiation. The calculation done in this experiment shows that irradiation dose of 17.4 Gy weaken the bacteria pathogenicity of S. agalactiae to the level of LD 50 . (author)

  5. Protein carriers of conjugate vaccines: characteristics, development, and clinical trials.

    Science.gov (United States)

    Pichichero, Michael E

    2013-12-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products.

  6. Effect of an Early Dose of Measles Vaccine on Morbidity Between 18 Weeks and 9 Months of Age: A Randomized, Controlled Trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Do, Vu An; Biering-Sorensen, Sofie; Fisker, Ane Bærent

    2017-01-01

    Background: Children in Guinea-Bissau receive measles vaccine (MV) at 9 months of age, but studies have shown that an additional dose before 9 months of age might have beneficial nonspecific effects. Within a randomized trial designed to examine nonspecific effects of early MV receipt on mortality......). Children were visited weekly from enrollment to age 9 months; the mother reported morbidity, and the field assistants examined the children. Using Cox and binomial regression models, we compared the 2 randomization groups. Results: Among the 1592 children, early measles vaccination was not associated...... with a higher risk of the well-known adverse events of fever, rash, and convulsions within the first 14 days. From 15 days after randomization to age 9 months, early measles vaccination was associated with reductions in maternally reported diarrhea (hazard ratio [HR], 0.89; 95% confidence interval [CI],.82-. 97...

  7. Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs

    Science.gov (United States)

    Geisbert, Joan B; Shedlock, Devon J; Xu, Ling; Lamoreaux, Laurie; Custers, Jerome H. H. V; Popernack, Paul M; Yang, Zhi-Yong; Pau, Maria G; Roederer, Mario; Koup, Richard A; Goudsmit, Jaap; Jahrling, Peter B; Nabel, Gary J

    2006-01-01

    Background Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. Methods and Findings To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 1010 particles, two logs lower than that used previously. Conclusions Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 1010 rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate. PMID:16683867

  8. Immune protection of nonhuman primates against Ebola virus with single low-dose adenovirus vectors encoding modified GPs.

    Directory of Open Access Journals (Sweden)

    Nancy J Sullivan

    2006-06-01

    Full Text Available Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd encoding the Ebola glycoprotein (GP and nucleoprotein (NP has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine.To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 10(10 particles, two logs lower than that used previously.Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 10(10 rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate.

  9. A review of immunogenicity and tolerability of live attenuated Hepatitis A vaccine in children

    Science.gov (United States)

    Rao, Sameer; Mao, J. S.; Motlekar, Salman; Fangcheng, Zhuang; Kadhe, Ganesh

    2016-01-01

    ABSTRACT Changing epidemiology of Hepatitis A virus (HAV) has led to an increased susceptibility of adolescents and adults to the infection. Vaccination can remarkably reduce the incidence and associated morbidity of HAV infection. This review is focused on the safety and efficacy of H2 strain derived live attenuated Hepatitis A vaccine. We found the vaccine to be highly immunogenic with minimal or negligible safety issues. Moreover, a single dose of live attenuated vaccine persists a long term immune response and can be a preferred option for developing countries. In 2014, Indian Academy of Paediatrics (IAP) also updated their recommendations for H2 vaccine as a single dose as against the previous 2 dose schedule. A focused approach to include the vaccine in national immunization program should be explored. PMID:27532370

  10. Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya

    2012-01-01

    Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher’s exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade ≥3 acute or late toxicity was 6.8% (14 patients). Fisher’s exact test resulted in significant median splits for grade ≥3 toxicity at V12 = 3.78 cm 3 (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm 3 (RR 13, P=.0013), V20 = 0.11 cm 3 (RR 6, P=0.01), and V22 = 0.0 cm 3 (RR 13, P=.0013). The median split for D2.5 cm 3 (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm 3 . One hundred percent (n = 7) of grade ≥4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade ≥3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation recall reactions are

  11. Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Moussazadeh, Nelson; Lis, Eric; Katsoulakis, Evangelia; Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily; Bilsky, Mark H.; Yamada, Yoshiya; Laufer, Ilya

    2015-01-01

    Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

  12. Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Moussazadeh, Nelson [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States); Lis, Eric [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Katsoulakis, Evangelia [Department of Radiation Oncology, New York Methodist Hospital, Brooklyn, New York (United States); Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bilsky, Mark H. [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States); Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Laufer, Ilya, E-mail: lauferi@mskcc.org [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States)

    2015-10-01

    Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

  13. Attention benefits after a single dose of metadoxine extended release in adults with predominantly inattentive ADHD.

    Science.gov (United States)

    Manor, Iris; Rubin, Jonathan; Daniely, Yaron; Adler, Lenard A

    2014-09-01

    To assess the first-dose effectiveness and tolerability of metadoxine extended release (MDX) in adults with predominantly inattentive attention-deficit/hyperactivity disorder (ADHD-PI). In this double-blind, placebo-controlled, crossover study, adults with ADHD-PI were randomized 1:1:1 to receive a single dose of MDX 1400 mg, MDX 700 mg, and placebo (ClinicalTrials.gov identifier: NCT01685281). The primary efficacy end point was the mean change in the Test of Variables of Attention (TOVA) ADHD score from baseline to 3 to 5 hours after drug administration. Secondary assessments included TOVA subscores, TOVA response rates (defined as an increase of 0.8 points in the TOVA ADHD score), and the Cambridge Neuropsychological Automated Test Battery. Safety assessments included adverse events and vital signs. The intention-to-treat population included 36 patients (52.8% men; mean age, 32 years). The efficacy of MDX 1400 mg was demonstrated by a statistically significant difference in the mean (± SD) change in the TOVA ADHD score at baseline to 3 to 5 hours after drug administration compared with placebo (2.0 [4.2]; P = 0.009). The TOVA response time variability subscore was significantly different between MDX 1400 mg and placebo (mean difference, 7.9 [19.2] points; P = 0.022). Significantly more adults responded to single-dose MDX 1400 mg versus placebo (97.1% vs 71.4%, P = 0.006). There were no statistically significant differences between MDX 700 mg and placebo on any measures. Exploratory analyses of the Cambridge Neuropsychological Automated Test Battery did not yield significant findings. Fatigue and headache were the 2 most frequently reported adverse events. There were no clinically significant abnormalities in laboratory values, vital signs measurements, Columbia-Suicide Severity Rating Scale scores, or electrocardiographic parameters. Single-dose MDX 1400 mg significantly improved sustained and selective attention in adults with ADHD-PI as measured by the TOVA

  14. Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

    Science.gov (United States)

    Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

    2016-01-01

    Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a

  15. Single dose toxicity and biodistribution studies of [{sup 18}F] fluorocholine

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Danielle C.; Santos, Priscilla F., E-mail: dcc@cdtn.br [Universidade Federal de Minas Gereais (INCT-MM/UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina. Instituto Nacional de Ciencia e Tecnologia de Medicina Molecular; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da, E-mail: radiofarmacoscdtn@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D., E-mail: cassalig@icb.ufmg.br [Universidade Federal de Minas Gerais (LPC/UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada

    2013-07-01

    [{sup 18}F]Fluorocholine ({sup 18}FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of {sup 18}FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of {sup 18}FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  16. Single oral dose toxicity test of platycodin d, a saponin from platycodin radix in mice.

    Science.gov (United States)

    Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang; Choi, Seong-Hun

    2011-12-01

    The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

  17. Comparison of single-dose and multiple-dose antibiotics for lower urinary tract infection in pregnancy.

    Science.gov (United States)

    Usta, Taner A; Dogan, Ozgur; Ates, Ugur; Yucel, Burak; Onar, Zehra; Kaya, Erdal

    2011-09-01

    To compare the efficacy of fosfomycin trometamol, cefuroxime axetil, and amoxicillin clavulanate antibiotics, and to assess the difference in patient compliance, in the treatment of urinary tract infections during pregnancy. Between September 2007 and May 2008, 90 out of 324 pregnant women with complaints of lower urinary tract infection, who were followed at the outpatient clinic or referred to the emergency department of Vakif Gureba Education and Research Hospital, were enrolled in a prospective study. Patients were randomized into 3 equal groups for treatment with single-dose fosfomycin trometamol, or 5-day courses of amoxicillin clavulanate or cefuroxime axetil. After follow-up, study data were obtained for 28, 27, and 29 patients, respectively. The treatment groups did not differ significantly in terms of demographics, clinical success rate, microbiological cure rate, or adverse effects. Significantly higher drug compliance was observed in the fosfomycin trometamol group than in the other 2 groups (PUTI as the standard course of treatment with amoxicillin clavulanate or cefuroxime axetil. Fosfomycin trometamol may be a preferable treatment for UTI because of its simpler use and better rates of compliance. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  18. A prospective study of hepatitis B vaccination - a comparison of responders versus nonresponders.

    LENUS (Irish Health Repository)

    Brown, Catherine M

    2012-02-01

    Herein we present one of the largest single-center reports of the response of hemodialysis patients to a two-vaccine hepatitis B virus vaccination protocol in a European dialysis population. A hepatitis B recombinant DNA vaccine, HBvaxPRO, was given at a dose of 40 microg intramuscularly using a four-dose schedule at 0, 1, 2, and 12 months. Responses were (1) a titer >100 mIU\\/mL = patient immune, (2) a titer level 10-99 mIU\\/mL = give a booster dose and recheck level 2 months later, and (3) 0 <\\/= 10 mIU\\/mL = repeat vaccination course using a different vaccine, Engerix-B. We compared responder groups in terms of titer levels for each vaccine and variables including age, gender, serum albumin, parathyroid hormone (PTH), calcium, phosphate, hemoglobin, years on dialysis, and type of dialysis access. Of the 176 patients who received the first vaccine course, 71 patients achieved immunity, that is, 40% uptake for the first vaccine. Of the 105 who failed, 72 received the second vaccine with 46 responders, that is, 64% uptake for the second vaccine. Overall, 143 of the 176 patients who entered the vaccination program completed the protocol with 117 achieving immunity, representing an 82% success rate. The only variable overall to show significance in achieving seroconversion was serum albumin (p = 0.03). Using a two-vaccine protocol, hepatitis B vaccination response was high in our population of end-stage renal disease patients.

  19. A prospective study of hepatitis B vaccination - a comparison of responders versus nonresponders.

    LENUS (Irish Health Repository)

    Brown, Catherine M

    2011-01-01

    Herein we present one of the largest single-center reports of the response of hemodialysis patients to a two-vaccine hepatitis B virus vaccination protocol in a European dialysis population. A hepatitis B recombinant DNA vaccine, HBvaxPRO, was given at a dose of 40 µg intramuscularly using a four-dose schedule at 0, 1, 2, and 12 months. Responses were (1) a titer >100 mIU\\/mL = patient immune, (2) a titer level 10-99 mIU\\/mL = give a booster dose and recheck level 2 months later, and (3) 0 ≤ 10 mIU\\/mL = repeat vaccination course using a different vaccine, Engerix-B. We compared responder groups in terms of titer levels for each vaccine and variables including age, gender, serum albumin, parathyroid hormone (PTH), calcium, phosphate, hemoglobin, years on dialysis, and type of dialysis access. Of the 176 patients who received the first vaccine course, 71 patients achieved immunity, that is, 40% uptake for the first vaccine. Of the 105 who failed, 72 received the second vaccine with 46 responders, that is, 64% uptake for the second vaccine. Overall, 143 of the 176 patients who entered the vaccination program completed the protocol with 117 achieving immunity, representing an 82% success rate. The only variable overall to show significance in achieving seroconversion was serum albumin (p = 0.03). Using a two-vaccine protocol, hepatitis B vaccination response was high in our population of end-stage renal disease patients.

  20. Immunogenicity and safety of a booster dose of the 13-valent pneumococcal conjugate vaccine in children primed with the 10-valent or 13-valent pneumococcal conjugate vaccine in the Czech Republic and Slovakia.

    Science.gov (United States)

    Urbancikova, Ingrid; Prymula, Roman; Goldblatt, David; Roalfe, Lucy; Prymulova, Karolina; Kosina, Pavel

    2017-09-12

    Although both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) are widely used, it is unclear how interchangeable they are in terms of immunogenicity. Two phase 3, open-label, multicenter studies were conducted to assess the immunogenicity and safety of a booster dose of PCV13 in children primed with PHiD-CV or PCV13. In the Czech Republic, 12-15-month-old children received a PCV13 booster after 3-dose priming with either PHiD-CV or PCV13. In Slovakia, 11-12-month-old children received PCV13 following 2-dose priming with either PHiD-CV or PCV13. Serum IgG concentrations were assessed by enzyme-linked immunosorbent assay and functional antibodies were assessed by opsonophagocytic assay (OPA) before the booster and at 1 and 12months afterward. The primary objective of these studies was to assess non-inferiority of OPA titers for serotype 19A in PHiD-CV-primed subjects compared to those in PCV13-primed children 1month post-booster. A total of 98 subjects in the Czech Republic and 89 subjects in Slovakia were included. One month after the PCV13 booster dose, the IgG and OPA immune responses to serotype 19A in subjects primed with 2 or 3 doses of PHiD-CV were non-inferior to those in subjects primed with PCV13. Non-inferior and persistent immune responses to most other vaccine serotypes were also observed after the PCV13 booster in PHiD-CV-primed subjects. No safety issues were raised in either study. Overall, robust IgG and OPA immunological responses were observed after booster vaccination with PCV13 in children primed with 2 or 3 doses of PHiD-CV or PCV13, including for serotypes not included in PHiD-CV. These results suggest that these vaccines are interchangeable in terms of safety and immunogenicity and that PCV13 can be used as a booster in the context of mixed schedules. (EudraCT numbers: 2012-005366-35 and 2012-005367-27). Copyright © 2017 Elsevier Ltd

  1. Pharmacokinetics of [14C]teicoplanin in male rats after single intravenous dose

    International Nuclear Information System (INIS)

    Bernareggi, A.; Cavenaghi, L.; Assandri, A.

    1986-01-01

    The pharmacokinetic profile of [ 14 C]teicoplanin was studied in male Sprague-Dawley rats given a single 10,000-U/kg intravenous dose. The disposition of the antimicrobial activity in the body was estimated by a three-compartment open model. Plasma concentration data were fitted to a three-exponent equation. The profile of total 14 C in plasma was similar to that of the microbiological activity. The cumulative recovery of total 14 C 5 days after drug administration averaged 76.3% of the administered dose in the urine and 8.7% in the feces. The residual dose remaining in the animal carcasses was 11.1%. Teicoplanin was widely distributed in the body. In almost all organs, the maximum concentration of [ 14 C]teicoplanin was already reached at the first time of killing, which was 0.25 h after the administration of drug. The liver, kidneys, skin, and fat contained most of the residual dose found in the animal carcasses 120 h after administration and behaved as a deep compartment with the adrenal glands and spleen

  2. Single fixed-dose oral dexketoprofen plus tramadol for acute postoperative pain in adults.

    Science.gov (United States)

    Derry, Sheena; Cooper, Tess E; Phillips, Tudor

    2016-09-22

    Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. A new combination of dexketoprofen (a nonsteroidal anti-inflammatory drug) plus tramadol (an opioid) has been tested in acute postoperative pain conditions. It is not yet licensed for use. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions. To assess the analgesic efficacy and adverse effects of a single fixed-dose of oral dexketoprofen plus tramadol, compared with placebo, for moderate to severe postoperative pain in adults, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. A secondary objective was to compare the combination with the individual analgesics alone. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via CRSO, MEDLINE via Ovid, and Embase via Ovid from inception to 31 May 2016. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. Randomised, double-blind trials of oral dexketoprofen plus tramadol administered as a single oral dose, for the relief of acute postoperative pain in adults, and compared to placebo. Two review authors independently considered trials for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) for dexketoprofen plus tramadol, compared with placebo with 95% confidence intervals (CI). We collected information on the number of participants with at least 50% of

  3. Successful administration of measles-rubella-mumps vaccine by graded challenge in a case with anaphylaxis after prior vaccination.

    Science.gov (United States)

    Tuncel, Tuba; Sancakli, Ozlem; Ozdogru, Ece

    2017-04-01

    Egg allergy is one of the most common food allergies during childhood along with cow's milk allergy. The measles-mumpsrubella (MMR) vaccine is included in the pediatric immunization schedule and contains egg protein. The currently accepted opinion is that the MMR vaccination should be done in a single dose under medical observation in patients with egg allergy. Although it is reported that the MMR vaccine is safe for that patients, there are some patients who developed anaphylaxis. Generally, the development of anaphylaxis after the previous vaccination is reported as a contraindication. We present a successful administration of MMR vaccine by gradually increased doses for a patient who developed anaphylaxis after the previous vaccination. Sociedad Argentina de Pediatría.

  4. Hardening of single crystals of magnesium by low neutron doses at 77 K

    International Nuclear Information System (INIS)

    Gonzalez, H.C.

    1984-01-01

    Radiation hardening in Mg single crystals at 77 K is studied with a microtensile machine operating in-situ in the CNEA reactor facility RA1. Experimental results show that the dose dependence of the yield stress is similar to that previously observed in irradiated Cu and Zn. The radiation-induced yield stress, due to the presence of radiation obstacles operating alone, increases according to a 0.5 power law. It adds algebraically to the athermal component of the initial yield stress, but is not exactly additive to the other thermally activated mechanisms. For doses higher than 4.5 x 10 16 neutrons/cm 2 , a strong instability in the deformation is observed. Post irradiation experiments in tensile tests performed with a hard machine show a continuous stress drop. This effect is attributed to the dislocation channeling phenomenon which takes place during the tensile test. (author)

  5. Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

    Directory of Open Access Journals (Sweden)

    Ičević Ivana Đ.

    2011-01-01

    Full Text Available Polyhydroxylated, water soluble, fullerenol C60(OH24 nano particles (FNP in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX (8 mg/kg (i.p. 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP, in H2O:DMSO (80:20, w/w solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

  6. Single-dose and fractionated irradiation of four human lung cancer cell lines in vitro

    International Nuclear Information System (INIS)

    Brodin, O.; Lennartsson, L.; Nilsson, S.

    1991-01-01

    Four established human lung cancer cell lines were exposed to single-dose irradiation. The survival curves of 2 small cell lung carcinomas (SCLC) were characterized by a limited capacity for repair with small and moderate shoulders with extrapolation numbers (n) of 1.05 and 1.60 respectively. Two non-small cell lung carcinoma (NSCLC) cell lines, one squamous cell (SQCLC) and one large cell (LCLC) had large shoulders with n-values of 73 and 15 respectively. The radiosensitivity when measured as D 0 did not, however, differ as much from cell line to cell line, with values from 1.22 to 1.65. The surviving fraction after 2 Gy (SF2) was 0.24 and 0.42 respectively in the SCLC cell lines and 0.90 and 0.88 respectively in the NSCLC cell lines. Fractionated irradiation delivered according to 3 different schedules was also investigated. All the schedules delivered a total dose of 10 Gy in 5 days and were applied in 1, 2 and 5 Gy dose fractions respectively. Survival followed the pattern found after single-dose irradiation; it was lowest in the SCLC cell line with the lowest SF and highest in the two NSCLC cell lines. In the SCLC cell lines all schedules were approximately equally efficient. In the LCLC and in the SQCLC cell lines, the 5 Gy schedule killed more cells than the 1 and 2 Gy schedules. The results indicate that the size of the shoulder of the survival curve is essential when choosing the most tumoricidal fractionation schedule. (orig.)

  7. PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    Science.gov (United States)

    Barbosa, Lorraine; Johnson, Shawn P; Papich, Mark G; Gulland, Frances

    2015-06-01

    Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions ( Zalophus californianus ) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions.

  8. Study of single dose toxic test of Sweet Bee Venom in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Hye-Chul, Yoon

    2010-12-01

    Full Text Available Objectives : This study was performed to analyse single dose toxicity of Sweet Bee Venom(Sweet BV extracted from the bee venom in Beagle dogs. Methods : All experiments were conducted under the regulations of Good Laboratory Practice (GLP at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of single dose toxicity of Sweet BV which was administered at the level of 9.0 ㎎/㎏ body weight which is 1300 times higher than the clinical application dosage as the high dosage, followed by 3.0 and 1.0 ㎎/㎏ as midium and low dosage, respectively. Equal amount of excipient(normal saline to the Sweet BV experiment groups was administered as the control group. Results : 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all the experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, brain, liver, lung, kidney, and spinal cords were removed and histologocal observation using H-E staining was conducted. In the histologocal observation of thigh muscle, cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes depend on the dose of Sweet BV. But the other organs did not showed in any abnormality. 5. The maximum dose of Sweet BV in Beagle dogs were over 9 ㎎/㎏ in this study. Conclusions : The above findings of this study suggest that Sweet BV is a relatively safe treatment medium. Further studies on the toxicity of Sweet BV should be conducted to yield more concrete evidences.

  9. Antibody persistence following meningococcal C conjugate vaccination in children and adolescents infected with human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Ana Cristina Cisne Frota

    2017-09-01

    Conclusion: Seroprotection at 12–18 months after single dose of MCC was low for both groups, and higher among individuals who presented baseline immunity. Among HIVI, vaccine should be administered after UVL is achieved.

  10. Novel vaccines to human rabies.

    Directory of Open Access Journals (Sweden)

    Hildegund C J Ertl

    Full Text Available Rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. Most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in Southeast Asia and Africa. Safe and efficacious vaccines are available to prevent rabies. However, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times for post-exposure prophylaxis (PEP. In cases of severe exposure, a regimen of vaccine combined with a rabies immunoglobulin (RIG preparation is required. The high incidence of fatal rabies is linked to a lack of knowledge on the appropriate treatment of bite wounds, lack of access to costly PEP, and failure to follow up with repeat immunizations. New, more immunogenic but less costly rabies virus vaccines are needed to reduce the toll of rabies on human lives. A preventative vaccine used for the immunization of children, especially those in high incidence countries, would be expected to lower fatality rates. Such a vaccine would have to be inexpensive, safe, and provide sustained protection, preferably after a single dose. Novel regimens are also needed for PEP to reduce the need for the already scarce and costly RIG and to reduce the number of vaccine doses to one or two. In this review, the pipeline of new rabies vaccines that are in pre-clinical testing is provided and an opinion on those that might be best suited as potential replacements for the currently used vaccines is offered.

  11. Development of γ dose rate monitor based on FPGA and single-chip microcomputer

    International Nuclear Information System (INIS)

    He Zhiguo; Ling Qiu; Guo Lanying; Yang Binhua

    2009-01-01

    A novelγdose rate monitor with multiple channels signal collection in which takes the FPGA as the core process chip and single-chip microcomputer as the data processor had been developed. This paper introduced the communication interface design between FPGA and MCU, and gave the data acquisition module and the function simulation chart designed by FPGA. In addition, the software and hardware design diagrams of MCU had been given in this paper. The maximum digitallization was carried on in the designing process. The experiments showed that the scheme for the system matched to the requests completely. (authors)

  12. Pharmacokinetic Effects of Antidrug Antibodies Occurring in Healthy Subjects After a Single Dose of Intravenous Infliximab.

    Science.gov (United States)

    Ehrenpreis, Eli D

    2017-12-01

    Infliximab pharmacokinetic studies have been performed in patients receiving chronic infliximab therapy. In these patients, infliximab antidrug antibodies (ADAs) increase infliximab clearance and decrease serum levels and drug efficacy. This study analyzed the pharmacokinetic effect of infliximab ADAs in healthy subjects receiving a single dose of intravenous infliximab. Data were obtained from a single-blind, parallel-group, single-dose study of healthy subjects receiving 5 mg/kg of intravenous SB2 (infliximab biosimilar), EU-sourced Remicade (EU-IFX) or US-sourced Remicade (US-IFX). Serum infliximab was measured at 1, 2, 3, 6, 12, 24, 48, and 72 h and at 5, 7, 14, 21, 28, 42, 56, and 70 days after administration. ADAs were measured pre-dose and at 29 and 71 days. Data from the first ten subjects randomized to each treatment arm were utilized for this study. A two-compartment model of the serum infliximab vs. time curve was developed using nonlinear regression. At 10 weeks, 11 subjects (37%) developed ADAs. ADAs were detected in four subjects after SB2, one subject after EU-IFX, and six subjects after US-IFX infusion. Of these, neutralizing antibodies occurred in one subject after SB2, in no subjects after EU-IFX, and in three subjects after US-IFX infusion. Infliximab clearance was increased in subjects with ADAs vs. those without ADAs (12.89 ± 2.69 vs. 9.90 ± 1.74 ml/h; p ADAs (282.4 ± 56.4 vs. 343.3 ± 61.9 h; p ADAs are common in healthy subjects after a single intravenous dose of infliximab and result in faster infliximab clearance, shorter elimination time, and lower serum infliximab levels. These data confirm that ADAs are common with biologic therapy and significantly impact the efficacy of these drugs.

  13. Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults.

    Science.gov (United States)

    Gaskell, Helen; Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

    2017-05-25

    This review is an update of "Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults" last updated in Issue 4, 2009. Ketoprofen is a non-selective nonsteroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions. To assess the efficacy and safety of single dose oral ketoprofen and oral dexketoprofen compared with placebo for acute postoperative pain, using methods that permit comparison with other analgesics evaluated in the same way, and criteria of efficacy recommended by an in-depth study at the individual patient level. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from 2009 to 28 March 2017. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. Randomised, double-blind, placebo-controlled trials of single dose orally administered ketoprofen or dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently considered studies for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH) with 95% confidence intervals (CI) for ketoprofen and dexketoprofen, compared with placebo, where there were sufficient data. We collected information on the number of participants with at least 50

  14. Immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal Nontypeable H. influenzae Protein D conjugate vaccine coadministered with DTPa-IPV-Hib in Dutch children

    NARCIS (Netherlands)

    Van Den Bergh, Menno R.; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H.; Sanders, Elisabeth A M

    2016-01-01

    Background: Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and

  15. Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

    Science.gov (United States)

    Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

    2015-01-01

    Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

  16. Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

    Directory of Open Access Journals (Sweden)

    Jing Hao

    Full Text Available Fixed-dose combinations (FDC contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed.Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients.New molecular entities (NMEs, new therapeutic biologics license applications (BLAs and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC and only already marketed drugs (Non-NMEs-FDC. Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed.During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31 after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39 before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24 years to the patent and exclusivity life of the single active ingredients in the combination.FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

  17. Pharmacokinetics of surotomycin from phase 1 single and multiple ascending dose studies in healthy volunteers.

    Science.gov (United States)

    Chandorkar, Gurudatt; Zhan, Qiao; Donovan, Julie; Rege, Shruta; Patino, Hernando

    2017-03-28

    Surotomycin, a novel, orally administered, cyclic, lipopeptide antibacterial in development for the treatment of Clostridium difficile-associated diarrhea, has demonstrated minimal intestinal absorption in animal models. Safety, tolerability, and plasma pharmacokinetics of single and multiple ascending oral doses (SAD/MAD) of surotomycin in healthy volunteers were characterized in two randomized, double-blind, placebo-controlled, phase 1 studies. Participants were sequentially enrolled into one of four SAD (500, 1000, 2000, 4000 mg surotomycin) or three MAD (250, 500, 1000 mg surotomycin twice/day for 14 days) cohorts. Ten subjects were randomized 4:1 into each cohort to receive surotomycin or placebo. Surotomycin plasma concentrations rose as dose increased (maximum plasma concentration [C max ]: 10.5, 21.5, 66.6, and 86.7 ng/mL). Systemic levels were generally low, with peak median surotomycin plasma concentrations observed 6-12 h after the first dose. In the MAD study, surotomycin plasma concentrations were higher on day 14 (C max : 25.5, 37.6, and 93.5 ng/mL) than on day 1 (C max : 6.8, 11.0, and 21.1 ng/mL for increasing doses), indicating accumulation. In the SAD study, <0.01% of the administered dose was recovered in urine. Mean surotomycin stool concentration from the 1000 mg MAD cohort was 6394 μg/g on day 5. Both cohorts were well tolerated with all adverse events reported as mild to moderate. Both SAD and MAD studies of surotomycin demonstrated minimal systemic exposure, with feces the primary route of elimination following oral administration; consistent with observations with similar compounds, such as fidaxomicin. Results of these phase 1 studies support the continued clinical development of surotomycin for the treatment of Clostridium difficile-associated diarrhea. NCT02835118 and NCT02835105 . Retrospectively registered, July 13 2016.

  18. Using the OSL single-aliquot regenerative-dose protocol with quartz extracted from building materials in retrospective dosimetry

    DEFF Research Database (Denmark)

    Bøtter-Jensen, L.; Solongo, S.; Murray, A.S.

    2000-01-01

    We report on the application of the single-aliquot regenerative-dose (SAR) protocol to the optically stimulated luminescence signal from quartz extracted from fired bricks acid unfired mortar in retrospective dosimetry. The samples came from a radioactive materials storage facility, with ambient...... dose rates of about 0.1 mGy/h. A detailed dose-depth profile was analysed from one brick, and compared with dose records from area TL dosemeters. Small-aliquot dose-distributions were analysed from the mortar samples; one associated with the exposed brick, and one from a remote site exposed only...

  19. Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance.

    Science.gov (United States)

    Lamers, C T J; Ramaekers, J G; Muntjewerff, N D; Sikkema, K L; Samyn, N; Read, N L; Brookhuis, K A; Riedel, W J

    2003-12-01

    Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition, psychomotor performance and driving-related task performance. Twelve healthy recreational ecstasy users participated in an experimental study conducted according to a double-blind, double-dummy, placebo-controlled three-way cross-over design. MDMA improved psychomotor performance, such as movement speed and tracking performance in a single task, as well as in a divided attention task. MDMA impaired the ability to predict object movement under divided attention. However, the inability to accurately predict object movement after MDMA may indicate impairment of particular performance skills relevant to driving. There was no effect of MDMA on visual search, planning or retrieval from semantic memory.

  20. Effect of experimental single Ancylostoma caninum and mixed infections of Trypanosoma brucei and Trypanosoma congolense on the humoural immune response to anti-rabies vaccination in dogs

    Directory of Open Access Journals (Sweden)

    Nwoha Rosemary Ijeoma Ogechi

    2015-06-01

    Full Text Available Objective: To determine the effect of Ancylostoma caninum (A. caninum and trypanosome parasites on the immune response to vaccination in dogs in endemic environments. Methods: Sixteen dogs for the experiment were grouped into 4 of 4 members each. Group I was the uninfected control one, and GPII was infected with A. caninum; GPIII was infected with A. caninum/Trypanosoma congolense (T. congolense, and GPIV was infected with Trypanosoma brucei (T. brucei/A. caninum. The dogs were first vaccinated with antirabies vaccine before infecting GPII, GPIII and GPIV with A. caninum which were done 4 weeks after vaccination. By 2-week post-vaccination, trypanosome parasites were superimposed on both GPIII and GPIV. A secondary vaccination was given to GPI, GPII, GPIII, and GPIV by Week 12 of the experiment (4 weeks post treatment. Results: The prepatent period was (3.00 ± 1.40 days, in the conjunct infection of T. brucei/ A. caninum. It was (9.00 ± 1.10 days, in conjunct T. congolense/A. caninum. The prepatent period of A. caninum was (14.0 ± 2.0 days in the single A. caninum group and (13.0 ± 1.0 days in the conjunct trypanosome/A. caninum. At the 1st week after vaccination, the antibody titer in all the vaccinated groups (GPI, GPII, GPIII, and GPIV significantly increased (P < 0.05 and peaked at the 3rd week after vaccination. Following infections, there were marked significant decreases (P < 0.05 in the antibody production against rabies in GPII, GPIII and GPIV. The significant decrease (P < 0.05 in antibody titer was highest in the conjunct groups (GPIII and GPIV compared to the single infection (GPII. Treatment with diminazene aceturate and mebendazole did not significantly improve antibody response in the dogs. A secondary vaccination administered at the 12th week after the primary vaccination significantly increased (P < 0.05 the antibody titer with a peak at the 3rd week after the secondary vaccination. Conclusions: It was therefore concluded

  1. Monitoring vaccine and non-vaccine HPV type prevalence in the post-vaccination era in women living in the Basilicata region, Italy.

    Science.gov (United States)

    Carozzi, Francesca; Puliti, Donella; Ocello, Cristina; Anastasio, Pasquale Silvio; Moliterni, Espedito Antonio; Perinetti, Emilia; Serradell, Laurence; Burroni, Elena; Confortini, Massimo; Mantellini, Paola; Zappa, Marco; Dominiak-Felden, Géraldine

    2018-01-15

    A large free-of-charge quadrivalent HPV (qHPV) vaccination program, covering four cohorts annually (women 11, 14, 17 and 24 years), has been implemented in Basilicata since 2007. This study evaluated vaccine and non-vaccine HPV prevalence 5-7 years post-vaccination program implementation in vaccinated and unvaccinated women. This population-based, cross-sectional study was conducted in the public screening centers of the Local Health Unit in Matera between 2012 and 2014. Cervical samples were obtained for Pap and HPV testing (HC2, LiPA Extra® assay) and participants completed a sociodemographic and behavioral questionnaire. Detailed HPV vaccination status was retrieved from the official HPV vaccine registry. HPV prevalence was described overall, by type and vaccination status. The association between HPV type-detection and risk/protective factors was studied. Direct vaccine protection (qHPV vaccine effectiveness [VE]), cross-protection, and type-replacement were evaluated in cohorts eligible for vaccination, by analyzing HPV prevalence of vaccine and non-vaccine types according to vaccination status. Overall, 2793 women (18-50 years) were included, 1314 of them having been in birth cohorts eligible for the HPV vaccination program (18- to 30-year-old women at enrolment). Among the latter, qHPV vaccine uptake was 59% (at least one dose), with 94% completing the schedule; standardized qHPV type prevalence was 0.6% in vaccinated versus 5.5% in unvaccinated women (P HPV, high-risk non-vaccine HPV, or any single non-vaccine type prevalence was observed between vaccinated and unvaccinated women. These results, conducted in a post-vaccine era, suggest a high qHPV VE and that a well-implemented catch-up vaccination program may be efficient in reducing vaccine-type infections in a real-world setting. No cross-protective effect or evidence of type-replacement was observed a few years after HPV vaccine introduction.

  2. Variation in provider vaccine purchase prices and payer reimbursement.

    Science.gov (United States)

    Freed, Gary L; Cowan, Anne E; Gregory, Sashi; Clark, Sarah J

    2009-12-01

    The purpose of this work was to collect data regarding vaccine prices and reimbursements in private practices. Amid reports of physicians losing money on vaccines, there are limited supporting data to show how much private practices are paying for vaccines and how much they are being reimbursed by third-party payers. We conducted a cross-sectional survey of a convenience sample of private practices in 5 states (California, Georgia, Michigan, New York, and Texas) that purchase vaccines for administration to privately insured children/adolescents. Main outcome measures included prices paid to purchase vaccines recommended for children and adolescents and reimbursement from the 3 most common, non-Medicaid payers for vaccine purchase and administration. Detailed price and reimbursement data were provided by 76 practices. There was a considerable difference between the maximum and minimum prices paid by practices, ranging from $4 to more than $30 for specific vaccines. There was also significant variation in insurance reimbursement for vaccine purchase, with maximum and minimum reimbursements for a single vaccine differing from $8 to more than $80. Mean net yield per dose (reimbursement for vaccine purchase minus price paid per dose) varied across vaccines from a low of approximately $3 to more than $24. Reimbursement for the first dose of vaccine administered ranged from $0 to more than $26, with a mean of $16.62. There is a wide range of prices paid by practices for the same vaccine product and in the reimbursement for vaccines and administration fees by payers. This variation highlights the need for individual practices to understand their own costs and reimbursements and to seek opportunities to reduce costs and increase reimbursements.

  3. Single Low-Dose Ionizing Radiation Induces Genotoxicity in Adult Zebrafish and its Non-Irradiated Progeny.

    Science.gov (United States)

    Lemos, J; Neuparth, T; Trigo, M; Costa, P; Vieira, D; Cunha, L; Ponte, F; Costa, P S; Metello, L F; Carvalho, A P

    2017-02-01

    This study investigated to what extent a single exposure to low doses of ionizing radiation can induce genotoxic damage in irradiated adult zebrafish (Danio rerio) and its non-irradiated F1 progeny. Four groups of adult zebrafish were irradiated with a single dose of X-rays at 0 (control), 100, 500 and 1000 mGy, respectively, and couples of each group were allowed to reproduce following irradiation. Blood of parental fish and whole-body offspring were analysed by the comet assay for detection of DNA damage. The level of DNA damage in irradiated parental fish increased in a radiation dose-dependent manner at day 1 post-irradiation, but returned to the control level thereafter. The level of DNA damage in the progeny was directly correlated with the parental irradiation dose. Results highlight the genotoxic risk of a single exposure to low-dose ionizing radiation in irradiated individuals and also in its non-irradiated progeny.

  4. Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.

    Science.gov (United States)

    Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

    2015-01-01

    In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.

  5. Randomized controlled trial comparing different single doses of intravenous paracetamol for placement of peripherally inserted central catheters in preterm infants

    NARCIS (Netherlands)

    D.W.E. Roofthooft (Daniella); S.H. Simons (Sinno); R.A. Lingen (Richard); D. Tibboel (Dick); J.N. van den Anker (John); I.K.M. Reiss (Irwin); M. van Dijk (Monique)

    2017-01-01

    markdownabstract__Background:__ The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different

  6. Single Dose Toxicity of Chukyu (spine-healing Pharmacopuncture Injection in the Muscle of Rats

    Directory of Open Access Journals (Sweden)

    Jeong Hohyun

    2014-03-01

    Full Text Available Objectives: This study was performed to analyze the single dose toxicity of Chukyu (spine-healing pharmacopuncture. Methods: All experiments were conducted at the Biotoxtech, an institution authorized to perform non-clinical studies under the regulations of Good Laboratory Practice (GLP regulations. Sprague-Dawley rats were chosen for the pilot study. Doses of Chukyu (spine-healing pharmacopuncture, 0.1, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was conducted under the approval of the Institutional Animal Ethic Committee. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues except in one case, where interstitial infiltrating macrophages were found in one female rat in the 0.5-mL/animal experimental group. Conclusion: The above findings suggest that treatment with Chukyu (spine-healing pharmacopuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

  7. Single Enteral Loading Dose of Phenobarbital for Achieving Its Therapeutic Serum Levels in Neonates

    Science.gov (United States)

    Turhan, Ali H.; Atici, Aytug; Okuyaz, Cetin; Uysal, Sercan

    2010-01-01

    Aim To investigate whether therapeutic serum drug levels may be achieved with a single enteral loading dose of phenobarbital. Methods The study was performed at the Mersin University Hospital in Turkey between April 2004 and August 2006, and included 29 newborn babies with seizure. After the acute treatment of the seizure with midazolam at a dose of 0.1 mg/kg, phenobarbital was administered by orogastric route at a loading dose of 20 mg/kg. Serum phenobarbital concentrations were measured at 0.5, 3, 6, and 12 hours after the loading. Serum phenobarbital levels between 10-30 μg/mL were considered as the therapeutic range. Results The serum phenobarbital levels reached therapeutic values in 9 (31%), 19 (66%), 21 (72%), and 23 (79%) patients at 0.5, 3, 6, and 12 hours after loading, respectively, while they did not reach therapeutic values in 6 patients (21%) after 12 hours. Four of the patients in whom there was no increase in serum phenobarbital levels had hypoxic-ischemic encephalopathy. Conclusion Enteral loading of phenobarbital can achieve therapeutic serum levels in the large majority of newborn babies with seizure and may be safely used in babies with the intact gastrointestinal tract. PMID:20564764

  8. Effects of single dose X-irradiation on the guinea-pig spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Knowles, J F [Medical Research Council, Harwell (UK). Radiobiological Research Unit

    1981-09-01

    Lumbar or cervical regions of the guinea-pig spinal cord were irradiated with a single dose of 250 kV X-rays. The latency for paralysis, whether of hind- or fore-limbs, and the histopathology of the radiation-induced cord lesions depended critically on the radiation dose. There were definite but only minor differences between the reactions of lumbar and cervical cord to the same radiation dose. After 30 or 40 Gy there was white matter necrosis but after 20 Gy widespread demyelination associated with vacuolar spaces occurred. After irradiation of the lumbar cord with 30-40 Gy, the lesions in the guinea-pig differed from those reported in the rat. White-matter necrosis in the guinea-pig cord was only occasionally associated with spinal nerve root necrosis, whereas in the rat, nerve-root necrosis with sparing of the white matter was the main lesion. After 20 Gy to the cervical or lumbar cord the guinea-pig showed widespread demyelination and vacuolation whereas in rats vascular lesions were the main result.

  9. Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

    Science.gov (United States)

    Wilhelmus, Micha Mm; Hay, Justin L; Zuiker, Rob Gja; Okkerse, Pieter; Perdrieu, Christelle; Sauser, Julien; Beaumont, Maurice; Schmitt, Jeroen; van Gerven, Joop Ma; Silber, Beata Y

    2017-02-01

    Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

  10. Palonosetron-A Single-Dose Antiemetic Adjunct for Hepatic Artery Radioembolization: A Feasibility Study

    International Nuclear Information System (INIS)

    Siddiqi, Nasir H.; Khan, Atif J.; Devlin, Phillip M.

    2009-01-01

    Nausea and vomiting may occur in a significant minority of patients following hepatic artery embolization with yttrium-90 spheres (K. T. Sato et al. Radiology 247:507-515, 2008). This encumbers human and economic resources and undercuts the assertion that it is as a well-tolerated outpatient treatment. A single intravenous dose of palonosetron HCl was administered before hepatic artery embolization with yttrium-90 spheres to ameliorate posttreatment nausea and vomiting, in 23 consecutive patients. The patients were discharged the day of procedure on oral antiemetics, steroids, and blockers of gastric acid release. All patients had clinical and laboratory evaluation at 2 weeks after the procedure. The data were gathered and reviewed retrospectively. At 2-week follow-up, none reported significant nausea, vomiting, additional antiemetic use, need for parenteral therapy, hospital readmission, or palonosetron-related side effects. All patients recovered from postembolization symptoms within a week after treatment. In conclusion, this retrospective study suggests that single-dose palonosetron is feasible, safe, and effective for acute and delayed nausea and vomiting in this group of patients. The added cost may be offset by benefits.

  11. Effect of a single dose of dextromethorphan on psychomotor performance and working memory capacity.

    Science.gov (United States)

    Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Ashor, Ammar Waham

    2012-04-01

    Previous studies show that the prolonged use