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1.
Vaccine ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31843270

RESUMO

BACKGROUND: Streptococcus pyogenes (group A Streptococcus, Strep A) is a widespread pathogen that continues to pose a significant threat to human health. The development of a Strep A vaccine remains an unmet global health need. One of the major vaccine strategies is the use of M protein, which is a primary virulence determinant and protective antigen. Multivalent recombinant M protein vaccines are being developed with N-terminal M peptides that contain opsonic epitopes but do not contain human tissue cross-reactive epitopes. METHODS: We completed a Phase I trial of a recombinant 30-valent M protein-based Strep A vaccine (Strep A vaccine, StreptAnova™) comprised of four recombinant proteins containing N-terminal peptides from 30 M proteins of common pharyngitis and invasive and/or rheumatogenic serotypes, adjuvanted with aluminum hydroxide. The trial was observer-blinded and randomized in a 2:1 ratio for intramuscular administration of Strep A vaccine or an alum-based comparator in healthy adult volunteers, at 0, 30 and 180 days. Primary outcome measures were assessments of safety, including assays for antibodies that cross-reacted with host tissues, and immunogenicity assessed by ELISA with the individual vaccine peptides and by opsonophagocytic killing (OPK) assays in human blood. RESULTS: Twenty-three Strep A-vaccinated participants and 13 controls completed the study. The Strep A vaccine was well-tolerated and there was no clinical evidence of autoimmunity and no laboratory evidence of tissue cross-reactive antibodies. The vaccine was immunogenic and elicited significant increases in geometric mean antibody levels to 24 of the 30 component M antigens by ELISA. Vaccine-induced OPK activity was observed against selected M types of Strep A in vaccinated participants that seroconverted to specific M peptides. CONCLUSION: The Strep A vaccine was well tolerated and immunogenic in healthy adults, providing strong support for further clinical development. [ClinicalTrials.gov NCT02564237].

2.
Lancet Infect Dis ; 19(9): 988-1000, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31399377

RESUMO

BACKGROUND: The adjuvanted recombinant zoster vaccine (Shingrix) can prevent herpes zoster in older adults and autologous haemopoietic stem cell transplant recipients. We evaluated the safety and immunogenicity of this vaccine in adults with haematological malignancies receiving immunosuppressive cancer treatments. METHODS: In this phase 3, randomised, observer-blind, placebo-controlled study, done at 77 centres worldwide, we randomly assigned (1:1) patients with haematological malignancies aged 18 years and older to receive two doses of the adjuvanted recombinant zoster vaccine or placebo 1-2 months apart during or after immunosuppressive cancer treatments, and stratified participants according to their underlying diseases. The co-primary objectives of the study were the evaluation of safety and reactogenicity of the adjuvanted recombinant zoster vaccine compared with placebo from the first vaccination up to 30 days after last vaccination in all participants; evaluation of the proportion of participants with a vaccine response in terms of anti-glycoprotein E humoral immune response to the adjuvanted recombinant zoster vaccine at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia; and evaluation of the anti-glycoprotein E humoral immune responses to the vaccine compared with placebo at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. We assessed immunogenicity in the per-protocol cohort for immunogenicity and safety in the total vaccinated cohort. The study is registered with ClinicalTrials.gov, number NCT01767467, and with the EU Clinical Trials Register, number 2012-003438-18. FINDINGS: Between March 1, 2013, and Sept 10, 2015, we randomly assigned 286 participants to adjuvanted recombinant zoster vaccine and 283 to placebo. 283 in the vaccine group and 279 in the placebo group were vaccinated. At month 2, 119 (80·4%, 95% CI 73·1-86·5) of 148 participants had a humoral vaccine response to adjuvanted recombinant zoster vaccine, compared with one (0·8%, 0·0-4·2) of 130 participants in the placebo group, and the adjusted geometric mean anti-glycoprotein E antibody concentration was 23 132·9 mIU/mL (95% CI 16 642·8-32 153·9) in the vaccine group and 777·6 mIU/mL (702·8-860·3) in the placebo group (adjusted geometric mean ratio 29·75, 21·09-41·96; p<0·0001) in all patients, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. Humoral and cell-mediated immune responses persisted above baseline until month 13 in all strata and, as expected, vaccine was more reactogenic than placebo (within 7 days after vaccination pain was reported by 221 [79·5%] of 278 vaccine group participants and 45 [16·4%] of 274 placebo group participants; fatigue was reported by 162 [58·3%] of 278 vaccine group participants and 102 [37·2%] of 274 placebo group participants). Incidences of unsolicited or serious adverse events, potential immune-mediated diseases, disease-related events, and fatal serious adverse events were similar between the groups. INTERPRETATION: The immunocompromised adult population with haematological malignancies is at high risk for herpes zoster. The adjuvanted recombinant zoster vaccine, which is currently licensed in certain countries for adults aged 50 years and older, is likely to benefit this population. FUNDING: GlaxoSmithKline Biologicals SA.

3.
Lancet Infect Dis ; 19(9): 1001-1012, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31399378

RESUMO

BACKGROUND: Patients who are immunocompromised because of malignancy have an increased risk of herpes zoster and herpes zoster-related complications. We aimed to investigate the efficacy and safety of an inactivated varicella zoster virus (VZV) vaccine for herpes zoster prevention in patients with solid tumour or haematological malignancies. METHODS: This phase 3, two-arm, randomised, double-blind, placebo-controlled, multicentre trial with an adaptive design was done in 329 centres across 40 countries. The trial included adult patients with solid tumour malignancies receiving chemotherapy and those with haematological malignancies, either receiving or not receiving chemotherapy. Patients were randomly assigned (1:1) to receive four doses of VZV vaccine inactivated by γ irradiation or placebo approximately 30 days apart. The patients, investigators, trial site staff, clinical adjudication committee, and sponsor's clinical and laboratory personnel were masked to the group assignment. The primary efficacy endpoint was herpes zoster incidence in patients with solid tumour malignancies receiving chemotherapy, which was assessed in the modified intention-to-treat population (defined as all randomly assigned patients who received at least one dose of inactivated VZV vaccine or placebo). The primary safety endpoint was serious adverse events up to 28 days after the fourth dose in patients with solid tumour malignancies receiving chemotherapy. Safety endpoints were assessed in all patients who received at least one dose of inactivated VZV vaccine or placebo and had follow-up data. This trial is registered (NCT01254630 and EudraCT 2010-023156-89). FINDINGS: Between June 27, 2011, and April 11, 2017, 5286 patients were randomly assigned to receive VZV vaccine inactivated by γ irradiation (n=2637) or placebo (n=2649). The haematological malignancy arm was terminated early because of evidence of futility at a planned interim analysis; therefore, all prespecified haematological malignancy endpoints were deemed exploratory. In patients with solid tumour malignancies in the modified intention-to-treat population, confirmed herpes zoster occurred in 22 of 1328 (6·7 per 1000 person-years) VZV vaccine recipients and in 61 of 1350 (18·5 per 1000 person-years) placebo recipients. Estimated vaccine efficacy against herpes zoster in patients with solid tumour malignancies was 63·6% (97·5% CI 36·4 to 79·1), meeting the prespecified success criterion. In patients with solid tumour malignancies, serious adverse events were similar in frequency across treatment groups, occurring in 298 (22·5%) of 1322 patients who received the vaccine and in 283 (21·0%) of 1346 patients who received placebo (risk difference 1·5%, 95% CI -1·7 to 4·6). Vaccine-related serious adverse events were less than 1% in each treatment group. Vaccine-related injection-site reactions were more common in the vaccine group than in the placebo group. In the haematological malignancy group, VZV vaccine was well tolerated and estimated vaccine efficacy against herpes zoster was 16·8% (95% CI -17·8 to 41·3). INTERPRETATION: The inactivated VZV vaccine was well tolerated and efficacious for herpes zoster prevention in patients with solid tumour malignancies receiving chemotherapy, but was not efficacious for herpes zoster prevention in patients with haematological malignancies. FUNDING: Merck & Co, Inc.

4.
Vaccine ; 37(36): 5466-5473, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31345638

RESUMO

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was recently shown to be effective against PCV13-type invasive pneumococcal disease (IPD) and pneumococcal community acquired pneumonia (CAPSpn) in healthy adults aged ≥65 years, prompting many countries to re-assess adult immunization. In Canada, the potential benefits of adult PCV13 immunization were unclear given anticipated herd immunity from PCV13 childhood immunization introduced since 2010. This study describes the serotype distribution and clinical outcomes of Canadian adults aged ≥16 years, who were hospitalized with CAPSpn and IPD from 2010 to 2015. METHODS: Active surveillance for CAP and IPD was performed in adult hospitals across five Canadian provinces. IPD was identified when Streptococcus pneumoniae was isolated from sterile sites. Bacteremic and non-bacteremic CAPSpn were identified using blood culture, and sputum culture or PCV13-specific urine antigen detection (UADPCV13), respectively. Serotype was assigned using Quellung reaction, PCR, or UADPCV13. RESULTS: Of 6687 CAP cases where a test was performed, S. pneumoniae positivity decreased from 15.9% in 2011 to 8.8% in 2014, but increased to 12.9% in 2015. CAPSpn attributed to PCV13 serotypes followed a similar trend, dropping from 8.3% in 2010 to 4.6% in 2014, but increasing to 6.3% in 2015. The decline was primarily attributed to serotypes 7F and 19A, and the proportional increase to serotype 3. Similar trends were noted for bacteremic and non-bacteremic CAPSpn. Serious outcomes such as 30-day mortality, intensive care unit admission, and requirement for mechanical ventilation were prominent in CAPSpn and IPD cases, but remained unchanged over the study years. CONCLUSION: Herd immunity afforded primarily by serotypes 7F and 19A appears to be partly masked by a concomitant proportional increase of serotype 3. Despite evidence of herd immunity, these PCV13 serotypes remain persistent in Canadian adults hospitalized with CAPSpn, and represent between 5 and 10% of all CAP in this patient population.

5.
Healthcare (Basel) ; 7(3)2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31311101

RESUMO

We sought to understand the association between social vulnerability and the odds of long-term care (LTC) placement within 30 days of discharge following admission to an acute care facility and whether this association varied based on age, sex, or pre-admission frailty. Patients admitted to hospital with acute respiratory illness were enrolled in the Canadian Immunization Research Network's Serious Outcomes Surveillance Network during the 2011/2012 influenza season. Participants (N = 475) were 65 years or older (mean = 78.6, SD = 7.9) and over half were women (58.9%). Incident LTC placement was rare (N = 15); therefore, we used penalized likelihood logistic regression analysis. Social vulnerability and frailty indices were built using a deficit accumulation approach. Social vulnerability interacted with frailty and age, but not sex. At age 70, higher social vulnerability was associated with lower odds of LTC placement at high levels of frailty (frailty index (FI) = 0.35; odds ratio (OR) = 0.32, 95% confidence interval (CI) = 0.09-0.94), but not at lower levels of frailty. At age 90, higher social vulnerability was associated with greater odds of LTC placement at lower levels of frailty (FI = 0.05; OR = 14.64, 95%CI = 1.55, 127.21 and FI = 0.15; OR = 7.26, 95%CI = 1.06, 41.84), but not at higher levels of frailty. Various sensitivity analyses yielded similar results. Although younger, frailer participants may need LTC, they may not have anyone advocating for them. In older, healthier patients, social vulnerability was associated with increased odds of LTC placement, but there was no difference among those who were frailer, suggesting that at a certain age and frailty level, LTC placement is difficult to avoid even within supportive social situations.

6.
Hum Vaccin Immunother ; 15(12): 2865-2872, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216205

RESUMO

In two pivotal efficacy studies (ZOE-50; ZOE-70), the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster (HZ).Adults aged ≥50 or ≥70 years (ZOE-50 [NCT01165177]; ZOE-70 [NCT01165229]) were randomized to receive 2 doses of RZV or placebo 2 months apart. Vaccine efficacy and safety were evaluated post-hoc in the pooled (ZOE-50/70) population according to the number and type of selected medical conditions present at enrollment.At enrollment, 82.3% of RZV and 82.7% of placebo recipients reported ≥1 of the 15 selected medical conditions. Efficacy against HZ ranged from 84.5% (95% Confidence Interval [CI]: 46.4-97.1) in participants with respiratory disorders to 97.0% (95%CI: 82.3-99.9) in those with coronary heart disease. Moreover, efficacy remained >90% irrespective of the number of selected medical conditions reported by a participant.As indicated by the similarity of the point estimates, this post-hoc analysis suggests that RZV efficacy remains high in all selected medical conditions, as well as with increasing number of medical conditions. No safety concern was identified by the type or number of medical conditions present at enrollment.

7.
Vaccine ; 37(18): 2482-2493, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30935742

RESUMO

BACKGROUND: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. METHODS: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. RESULTS: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. CONCLUSIONS: No safety concerns arose, supporting the favorable benefit-risk profile of RZV.

8.
Clin Infect Dis ; 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30843046

RESUMO

BACKGROUND: The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. METHODS: In this phase III, randomized (1:1), observer-blind, multicenter trial (NCT02058589), RT recipients were enrolled and received 2 doses of RZV or Placebo 1-2 months (M) apart 4-18M post-transplant. Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post-dose 1, and 1M and 12M post-dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post-each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post-dose 2. RESULTS: 264 participants (RZV: 132; Placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across post-vaccination time points and persisted above pre-vaccination baseline 12M post-dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, SAEs, and pIMDs were similar between groups. CONCLUSIONS: RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M post-vaccination. No safety concerns arose.

9.
J Infect Dis ; 219(11): 1799-1803, 2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-30715452

RESUMO

This analysis focused on long-term cross-reactive immunogenicity against nonvaccine human papillomavirus (HPV) types 31 and 45 following 2 doses of AS04-adjuvanted HPV-16/18 vaccine in girls aged 9-14 years or following 3 doses in women aged 15-25 years, for up to 3 years (HPV-070 study) and up to 5 years (HPV-048 study) after the first vaccination. Both schedules elicited antibodies against HPV-31 and HPV-45 up to 5 years after first dose. The antibody concentration was similar in young girls as compared to women. Specific CD4+ T-cell and B-cell responses to HPV-31 and HPV-45 at month 36 were similar across groups. Clinical trials registration: NCT01381575 and NCT00541970.

10.
Cancer ; 125(8): 1301-1312, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30707761

RESUMO

BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) has demonstrated >90% efficacy against herpes zoster in adults ≥50 years of age and 68% efficacy in autologous hematopoietic stem cell transplant recipients ≥18 years of age. We report the immunogenicity and safety of RZV administered to patients with solid tumors (STs) before or at the start of a chemotherapy cycle. METHOD: In this phase 2/3 observer-blind, multicenter study (NCT01798056), patients with STs who were ≥18 years of age were randomized (1:1) to receive 2 doses of RZV or placebo 1-2 months apart and stratified (4:1) according to the timing of the first dose with respect to the start of a chemotherapy cycle (first vaccination 8-30 days before the start or at the start [±1 day] of a chemotherapy cycle). Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4+ T cell frequencies, and vaccine response rates (VRRs) were assessed 1 month after dose 1 and 1 and 12 months after dose 2. Reactogenicity and safety were assessed in the total vaccinated cohort through 12 months after dose 2. RESULTS: There were 232 participants in the total vaccinated cohort, 185 participants in the according-to-protocol cohort for humoral immunogenicity, and 58 participants in the according-to-protocol cohort for cell-mediated immunogenicity. Postvaccination anti-gE antibody concentrations, gE-specific CD4+ T cell frequencies and VRRs were higher in RZV recipients than in placebo recipients. Solicited adverse events (AEs) were more frequent among RZV recipients than placebo recipients. Incidence of unsolicited AEs, serious AEs, fatalities, and potential immune-mediated diseases were similar between RZV and placebo recipients. CONCLUSION: RZV was immunogenic in patients with STs receiving immunosuppressive chemotherapies. Humoral and cell-mediated immune responses persisted 1 year after vaccination. No safety concerns were identified.

11.
Chest ; 155(1): 69-78, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30616737

RESUMO

BACKGROUND: The effectiveness of influenza vaccination in reducing influenza-related hospitalizations among patients with COPD is not well described, and influenza vaccination uptake remains suboptimal. METHODS: Data were analyzed from a national, prospective, multicenter cohort study including patients with COPD, hospitalized with any acute respiratory illness or exacerbation between 2011 and 2015. All patients underwent nasopharyngeal swab screening with polymerase chain reaction (PCR) testing for influenza. The primary outcome was an influenza-related hospitalization. We identified influenza-positive cases and negative control subjects and used multivariable logistic regression with a standard test-negative design to estimate the vaccine effectiveness for preventing influenza-related hospitalizations. RESULTS: Among 4,755 hospitalized patients with COPD, 4,198 (88.3%) patients with known vaccination status were analyzed. The adjusted analysis showed a 38% reduction in influenza-related hospitalizations in vaccinated vs unvaccinated individuals. Influenza-positive patients (n = 1,833 [38.5%]) experienced higher crude mortality (9.7% vs 7.9%; P = .047) and critical illness (17.2% vs 12.1%; P < .001) compared with influenza-negative patients. Risk factors for mortality in influenza-positive patients included age > 75 years (OR, 3.7 [95% CI, 0.4-30.3]), cardiac comorbidity (OR, 2.0 [95% CI, 1.3-3.2]), residence in long-term care (OR, 2.6 [95% CI, 1.5-4.5]), and home oxygen use (OR, 2.9 [95% CI, 1.6-5.1]). CONCLUSIONS: Influenza vaccination significantly reduced influenza-related hospitalization among patients with COPD. Initiatives to increase vaccination uptake and early use of antiviral agents among patients with COPD could reduce influenza-related hospitalization and critical illness and improve health-care costs in this vulnerable population. TRIAL REGISTRY: ClinicalTrials.govNo.:NCT01517191; URL www.clinicaltrials.gov.


Assuntos
Hospitalização/tendências , Vírus da Influenza A/imunologia , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Medição de Risco/métodos , Vacinação/métodos , Adolescente , Adulto , Idoso , Canadá/epidemiologia , Comorbidade , Feminino , Seguimentos , Humanos , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida/tendências , Adulto Jovem
12.
Drugs Aging ; 36(1): 29-37, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30411283

RESUMO

Influenza can lead to serious illness, particularly for older adults. In addition to short-term morbidity and mortality during the acute infection, recovery can be prolonged and often incomplete. This may lead to persistent declines in health and function, including catastrophic disability, which has dramatic implications for the well-being and support needs of older adults and their caregivers. All of this means that prevention of infection and effective treatment when illness has occurred are of paramount importance. In this narrative review, we discuss the effectiveness of influenza vaccines for the prevention of influenza illness and serious outcomes in older adults. We review evidence of vaccine effectiveness for older adults in comparison with younger age groups, and also highlight the importance of frailty as a determinant of vaccine effectiveness. We then turn our attention to the question of why older and frailer individuals have poorer vaccine responses, and consider changes in immune function and inflammatory responses. This sets the stage for a discussion of newer influenza vaccine products that have been developed with the aim of enhancing vaccine effectiveness in older adults. We review the available evidence on vaccine efficacy, effectiveness and cost benefits, consider the potential place of these innovations in clinical geriatric practice, and discuss international advisory committee recommendations on influenza vaccination in older adults. Finally, we highlight the importance of influenza prevention to support healthy aging, along with the need to improve vaccine coverage rates using available vaccine products, and to spur development of better influenza vaccines for older adults in the near future.


Assuntos
Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Vacinação , Idoso , Análise Custo-Benefício , Humanos , Resultado do Tratamento
13.
Pharm. pract. (Granada, Internet) ; 16(4): 0-0, oct.-dic. 2018. tab
Artigo em Inglês | IBECS | ID: ibc-180988

RESUMO

Background: The expansion of pharmacist scope of practice to include provision of immunizations has occurred or is being considered in various countries. There are limited data evaluating the experiences of Canadian pharmacists in their role as immunizers. Objective: To describe the experiences of pharmacists in the Canadian province of New Brunswick as immunizers, including vaccines administered and perceived barriers and facilitators to providing immunizations. Methods: An anonymous, self-administered, web-based questionnaire was offered via email by the New Brunswick Pharmacists' Association to all its members. The survey tool was adapted, with permission, from a tool previously used by the American Pharmacists Association and validated using content validity and test-retest reproducibility. Pharmacist reported immunization activities and perceived facilitators and barriers to providing immunization services were assessed. Results: Responses from 168 (response rate of 26%) were evaluable. Approximately 90% of respondents worked in community practice full time, 65% were female and 44% were practicing for 20 or more years. Greater than 75% reported administering: hepatitis A and B, influenza, and zoster vaccines. The majority of respondents felt fully accepted (agreed or strongly agreed) as immunization providers by patients, local physicians, and the provincial health department (97%, 70%, and 78%, respectively). Most commonly reported barriers were: lack of a universally funded influenza immunization program, insufficient staffing and space, and concerns around reimbursement for services. Conclusions: Pharmacists in New Brunswick, Canada are actively participating in the provision of a variety of immunizations and felt fully supported by patients and other healthcare providers. Barriers identified may provide insight to other jurisdictions considering expanding the role of pharmacists as immunizers


No disponible


Assuntos
Humanos , Assistência Farmacêutica/tendências , Vacinação/tendências , Imunização/tendências , Canadá/epidemiologia , Programas de Imunização/organização & administração , Prática Profissional/organização & administração , Inquéritos e Questionários/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde
14.
Plasmid ; 98: 45-51, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-30217467

RESUMO

BACKGROUND: Serotyping of Streptococcus pneumoniae is an integral part of disease surveillance, with over 92 serotypes characterized to date using traditional serotyping. To identify the most predominant disease causing serotypes, molecular serotyping methods are now increasingly being used, like conventional and real-time multiplex PCR (cmPCR and rmPCR, respectively). Given that cmPCR consists of eight reactions spanning 41 targets, and rmPCR consists of seven triplex reactions, standardizing positive controls for these assays is challenging. As such, a 43-target plasmid for cmPCR (pSpn-CM1) and a 23 target plasmid for rmPCR (pSpn-RM1) were designed and validated. METHODS: Plasmid pSpn-RM1 was designed and synthesized as chimeric DNA sequences to include all PCR target primer binding sites sequences for cmPCR. Plasmid pSpn-RM1 consisted of all primer and probe sequences required for rmPCR. Additional targets (lytA and cpsA) were included in both plasmids for quantification, following their propagation and purification from Escherichia coli. RESULTS: When tested using the cmPCR reactions, all targets could be reproducibly be detected using pSpn-CM1 as template, with good amplicon visibility at a concentration of 1.4 (± 0.3) × 105 copies/ml was used. For the rmPCR reactions, all targets were reproducibly amplified with a concentration of 1.1 (± 0.2) × 104 copies/ml of pSpn-RM1, and the PCR efficiency for each target was equivalent to DNA extracted from representative S. pneumoniae serotypes. CONCLUSIONS: These quantifiable multi-target plasmids simplify the preparation of controls for PCR-based serotyping of S. pneumoniae, and methods herein could be extended to other highly multiplexed PCR assays.


Assuntos
Técnicas de Tipagem Bacteriana/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Plasmídeos/genética , Infecções Pneumocócicas/diagnóstico , Controle de Qualidade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Streptococcus pneumoniae/classificação , DNA Bacteriano , Ensaios de Triagem em Larga Escala , Humanos , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação
15.
Clin Infect Dis ; 67(7): 1063-1071, 2018 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-30010773

RESUMO

Background: Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant. Methods: In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant's immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses. Results: Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM. Conclusions: This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series. Clinical Trials Registration: NCT00553228.


Assuntos
Anticorpos Antibacterianos/sangue , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Adulto , Difteria/prevenção & controle , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/efeitos adversos , Feminino , Humanos , Recém-Nascido , Gravidez , Tétano/prevenção & controle , Coqueluche/prevenção & controle , Adulto Jovem
16.
BMC Med Res Methodol ; 18(1): 59, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29925324

RESUMO

BACKGROUND: Web-based surveys have become increasingly popular but response rates are low and may be prone to selection bias. How people are invited to participate may impact response rates and needs further study as previous evidence is contradictory. The purpose of this study was to determine whether response to a web-based survey of healthcare workers would be higher with a posted or an emailed invitation. We also report results of the pilot study, which aims to estimate the percentage of adults vaccinated against influenza who report recurrent systemic adverse events (the same systemic adverse event occurring successively following receipt of influenza vaccines). METHODS: The pilot study was conducted in November 2016 in Toronto, Canada. Members of a registry of adults (18 years and older and predominantly healthcare workers) who volunteered to receive information regarding future studies about influenza were randomly assigned to receive either an email or postal invitation to complete a web-based survey regarding influenza vaccinations. Non-respondents received one reminder using the same mode of contact as their original invitation. RESULTS: The overall response rate was higher for those sent the invitation by email (34.8%) than by post (25.8%; p < 0.001) and for older versus younger participants (ptrend < 0.001). Of those who responded, 387/401 had been vaccinated against influenza at least once since adulthood. Of those responding to the question, 70/386 (18.1%) reported a systemic adverse event after their most recent influenza vaccine including 22 (5.7%) who reported a recurring systemic event. Systemic adverse events were reported more often by males 18-49 years old than by other groups (p = 0.01). Recurrent systemic adverse events were similar by age and sex with muscle ache being the most commonly reported recurrent reaction. More respondents who reported only a local adverse event (93.1%) planned to be vaccinated again next year than those with a systemic adverse event (69.7%; p = 0.04). CONCLUSIONS: In this convenience sample of registry volunteers, response rates were generally low, but were higher for the emailed than posted invitations and for older than younger adults.


Assuntos
Pessoal de Saúde/estatística & dados numéricos , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Internet , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Vacinas contra Influenza/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Vacinação/estatística & dados numéricos , Adulto Jovem
17.
Vaccine ; 36(16): 2166-2175, 2018 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-29548608

RESUMO

BACKGROUND: Ongoing assessment of influenza vaccine effectiveness (VE) is critical to inform public health policy. This study aimed to determine the VE of trivalent influenza vaccine (TIV) for preventing influenza-related hospitalizations and other serious outcomes over three consecutive influenza seasons. METHODS: The Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) conducted active surveillance for influenza in adults ≥16 years (y) of age during the 2011/2012, 2012/2013 and 2013/2014 seasons in hospitals across Canada. A test-negative design was employed: cases were polymerase chain reaction (PCR)-positive for influenza; controls were PCR-negative for influenza and were matched to cases by date, admission site, and age (≥65 y or <65 y). All cases and controls had demographic and clinical characteristics (including influenza immunization status) obtained from the medical record. VE was estimated as 1-OR (odds ratio) in vaccinated vs. unvaccinated patients × 100%. The primary outcome was VE of TIV for preventing laboratory-confirmed influenza-related hospitalization; secondary outcomes included VE of TIV for preventing influenza-related intensive care unit (ICU) admission/mechanical ventilation, and influenza-related death. RESULTS: Overall, 3394 cases and 4560 controls were enrolled; 2078 (61.2%) cases and 2939 (64.5%) controls were ≥65 y. Overall matched, adjusted VE was 41.7% (95% Confidence Interval (CI): 34.4-48.3%); corresponding VE in adults ≥65 y was 39.3% (95% CI: 29.4-47.8%) and 48.0% (95% CI: 37.5-56.7%) in adults <65 y, respectively. VE for preventing influenza-related ICU admission/mechanical ventilation in all ages was 54.1% (95% CI: 39.8-65.0%); in adults ≥65 y, VE for preventing influenza-related death was 74.5% (95% CI: 44.0-88.4%). CONCLUSIONS: While effectiveness of TIV to prevent serious outcomes varies year to year, we demonstrate a statistically significant and clinically important TIV VE for preventing hospitalization and other serious outcomes over three seasons. Public health messaging should highlight the overall benefit of influenza vaccines over time while acknowledging year to year variability. ClinicalTrials.gov Identifier: NCT01517191.


Assuntos
Hospitalização , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Estações do Ano , Idoso , Idoso de 80 Anos ou mais , Canadá/epidemiologia , Estudos de Casos e Controles , Comorbidade , Feminino , História do Século XXI , Humanos , Programas de Imunização , Vírus da Influenza A/classificação , Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/história , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Fatores de Risco , Vacinação
18.
Am J Dermatopathol ; 40(5): 383-385, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29140806

RESUMO

A healthy 50-year-old woman had a tattoo performed on the posterior aspect of her neck and another on the dorsum of her left foot. Several weeks later, she noted redness, tenderness, and intense pruritis at both tattoo sites. Treatment with cephalexin and hydrocortisone cream was instituted, without success. Within a few months, the red, but not black, pigment had disappeared from both tattoos and was replaced by pale areas of scarring. Persistently enlarged left supraclavicular and suboccipital lymph nodes were excised 7 and 10 months after receipt of the tattoos, respectively. The nodes were pigmented on gross examination, and on microscopy, a granuloma annulare-like reaction was observed. Normal lymphoid tissue was seen to be replaced by large palisading granulomas with central degenerative change, abundant stromal mucin, and scattered deposits of tattoo pigment. Histochemical stains, tissue culture, and serological studies revealed no evidence of infection. There are rare reports of granuloma annulare-like reactions in tattoos, and these are believed to represent delayed-type hypersensitivity reactions. Our case is unique in the observation of this reaction pattern in regional lymph nodes, and it expands the spectrum of complications known to be associated with tattoos.


Assuntos
Corantes/efeitos adversos , Granuloma Anular/etiologia , Granuloma Anular/patologia , Linfonodos/patologia , Tatuagem/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade
19.
Influenza Other Respir Viruses ; 12(2): 232-240, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29125689

RESUMO

BACKGROUND: Consideration of cost determinants is crucial to inform delivery of public vaccination programs. OBJECTIVES: To estimate the average total cost of laboratory-confirmed influenza requiring hospitalization in Canadians prior to, during, and 30 days following discharge. To analyze effects of patient/disease characteristics, treatment, and regional differences in costs. METHODS: Study utilized previously recorded clinical characteristics, resource use, and outcomes of laboratory-confirmed influenza patients admitted to hospitals in the Serious Outcomes Surveillance (SOS), Canadian Immunization Research Network (CIRN), from 2010/11 to 2012/13. Unit costs including hospital overheads were linked to inpatient/outpatient resource utilization before and after admissions. RESULTS: Dataset included 2943 adult admissions to 17 SOS Network hospitals and 24 Toronto Invasive Bacterial Disease Network hospitals. Mean age was 69.5 years. Average hospital stay was 10.8 days (95% CI: 10.3, 11.3), general ward stays were 9.4 days (95% CI: 9.0, 9.8), and ICU stays were 9.8 days (95% CI: 8.6, 11.1) for the 14% of patients admitted to the ICU. Average cost per case was $14 612 CAD (95% CI: $13 852, $15 372) including $133 (95% CI: $116, $150) for medical care prior to admission, $14 031 (95% CI: $13 295, $14 768) during initial hospital stay, $447 (95% CI: $271, $624) post-discharge, including readmission within 30 days. CONCLUSION: The cost of laboratory-confirmed influenza was higher than previous estimates, driven mostly by length of stay and analyzing only laboratory-confirmed influenza cases. The true per-patient cost of influenza-related hospitalization has been underestimated, and prevention programs should be evaluated in this context.


Assuntos
Custos de Cuidados de Saúde , Recursos em Saúde , Hospitalização , Influenza Humana/economia , Influenza Humana/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá/epidemiologia , Feminino , Humanos , Influenza Humana/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
J Microbiol Methods ; 144: 99-106, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29162393

RESUMO

Serotyping of Streptococcus pneumoniae is important to monitor disease epidemiology and assess the impact of pneumococcal vaccines. Traditionally, the Quellung reaction used serotype-specific antibodies to classify S. pneumoniae based on differences in capsular antigens. More recently, PCR-based serotype deduction relying on serotype-specific capsule biosynthesis genes has been broadly applied for pneumococcal surveillance. However, PCR-based serotyping lacks discrimination for certain S. pneumoniae serotypes, including the differentiation of serotype 22F from 22A, and serotype 33F from 33A and 37. Serotypes 22F and 33F are emerging serotypes that are absent in the currently licensed 13-valent pneumococcal conjugate vaccine, but present in the new candidate 15-valent formulation. This study validated novel PCR reactions to detect and discriminate S. pneumoniae serotypes 22F and 33F. In order to differentiate S. pneumoniae serotypes 22F or 33F from genetically similar serotypes, two novel PCR reactions were designed and validated. The specificity of all PCR targets was evaluated using all 92 different S. pneumoniae serotypes, as well as 32 other streptococci. Reproducibility was evaluated using geographically and genetically diverse strains of S. pneumoniae serotypes 22F and 22A, or serotypes 33F, 33A, and 37 that were previously characterized by reputable reference laboratories. Overall, S. pneumoniae serotypes 22F and 33F could be accurately and reproducibly be detected and discriminated using PCR alone. Such a molecular serotyping approach provides a valuable diagnostic tool that is feasible in any molecular laboratory, to enable pneumococcal serotype surveillance and subsequent assessment of the impact of the new 15-valent candidate pneumococcal vaccine.


Assuntos
Reação em Cadeia da Polimerase/métodos , Sorogrupo , Sorotipagem/métodos , Streptococcus pneumoniae/classificação , Cápsulas Bacterianas/genética , Cápsulas Bacterianas/imunologia , Técnicas de Tipagem Bacteriana/métodos , Humanos , Tipagem Molecular/métodos , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Vacinas Pneumocócicas/uso terapêutico , Reprodutibilidade dos Testes , Análise de Sequência de DNA , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/isolamento & purificação , Vacinas Conjugadas/imunologia , Vacinas Conjugadas/uso terapêutico , Sequenciamento Completo do Genoma
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