Background: Over the last twenty years the incidence of herpes zoster (HZ) infection, also known as shingles, has been increasing among adults for unknown reasons. The economic burden of HZ is currently estimated at over $1 billion per year in the United States (U.S.) and is expected to increase as the susceptible adult population ages. HZ is caused by a re-activation of the varicella zoster virus (VZV), chicken pox, and more than 95% of adults living today carry the virus with a lifetime risk of 1 in 3 for developing HZ. In 2006 the FDA approved a vaccine for the prevention of HZ in adults 60 years and older and in 2011 approval was expanded to include adults age 50-59 years. Since 2006 rates of adult immunization for HZ have been modest, as of 2015 approximately two-thirds of the US population ≥ 60 are still unvaccinated and more than 94% of those ages 50-59 have not been vaccinated. There is now accumulating evidence of a significantly elevated risk of ischemic stroke (IS) within the first 12 months following infection with HZ. Every 40 seconds someone in the U.S. suffers a stroke with an estimated 795,000 strokes per year. In the U.S. stroke is a significant cause of disability with costs estimated at $33 billion per year including cost of healthcare, medication, and lost productivity. As the population in the U.S ages, the risk of both HZ infection and stroke will increase significantly thus impacting mortality, morbidity, and healthcare costs. The CDC Advisory Committee for Immunization Practices (ACIP) currently recommends routine vaccination against HZ for adults ≥ 60 but does not recommend vaccination for adults age 50-59 years and does not provided any guidance or recommendations for adults who may be at increased risk of stroke associated with HZ infection. The current ACIP vaccination recommendations for HZ are predominately based on clinical trial efficacy data and cost-effectiveness analyses (CEAs) in adults ≥ 60. These prior analyses did not included costs associated with the recent evidence demonstrating increased risk of stroke up to one year following HZ infection. Aims: The objectives of this study were as follows; 1) To assess the cost-effectiveness of a targeted HZ vaccination strategy for adults age 50-59 years at increased cardiovascular (CV) risk in whom vaccination is approved but not recommended; 2) To develop a white paper directed at payers, providers, and policy makers translating the findings from the analysis into appropriate population health dissemination, implementation, and adoption priority recommendations. Methods: A decision analytic Markov Model (MM) was used to compare costs and outcomes between two vaccination strategies; usual-care (no current vaccine recommendation) and targeted vaccination in adults age 50-59 years with cardiovascular disease (CVD) in a hypothetical cohort of 100,000 adults age 50-59 years. The private payer perspective was used as it best represents this population of adults age 50-59 years who are predominately employed and covered under employer sponsored commercial insurance. The simulated cohort was assessed for incidence of IS within 12 months following HZ infection occurring within the fifth decade of life. Risk was assessed from the age at entry to the analysis, median age 55, up to age 60 using TreeAge Pro 2017 software. The cohort was then aged out to 100 years or death, whichever came first. Costs were calculated using 2016 U.S. dollars. Findings: As it relates to aim one, compared to usual-care targeting HZ vaccination in adults age 50-59 years with prevalent CVD was cost-effective with an incremental cost-effectiveness ratio (ICER) of $55,517 per quality of life-year (QALY) gained which falls well below the standard willingness-to-pay (WTP) threshold of $100,000 utilized in previous HZ CEAs (Le & Rothberg, 2015, 2016; Pellissier, Brisson, & Levin, 2007). The incremental cost of vaccinating the target population using a benchmark vaccination rate of 60% was $30.59 per person compared to $12.98 in the usual-care group with ICERs of $55,517 and $55,470 respectively. Moreover, when comparing the cost of universal vaccination in the entire 50-59 year old cohort cost-effectiveness was maintained with an incremental cost of $176.51 per person and an ICER of $55,523. Adopting the targeted strategy resulted in 162 fewer cases of HZ and 14 fewer strokes per 100,000 persons. Regarding aim two, following safety and efficacy, cost-effectiveness analysis are considered an essential metric in vaccine policy making and a substantial driver of vaccine adoption by policymakers, payers, and providers. Translating these favorable cost-effectiveness findings to policymakers, payers, and providers is necessary to help close the adoption curve gap in order to facilitate and inform effective and timely implementation strategies for HZ vaccination in this targeted population. Conclusions: This study demonstrated that targeted HZ vaccination in patients age 50-59 years at increased CV risk is cost-effective and thus updating ACIP policy recommendations regarding vaccination in this population for whom the vaccine is currently FDA approved but not recommended should be considered. Furthermore, this study showed that universal vaccination in the general 50-59 year old population is cost-effective. Given the very limited data on cost-effectiveness of HZ vaccination in adults age 50-59 years, which has resulted in a lack of recommendation for this population, and recent evidence of IS risk the results of this study demonstrating cost-effectiveness of a targeted HZ vaccination strategy directly support the National Adult Immunization Plan (NAIP) to improve adult immunization uptake by providing economic evaluations which can be used to inform policymakers, payers, and providers.

Made available in DSpace on 2015-09-25T12:22:06Z (GMT). No. of bitstreams: 1 PDF - Maria Soraya Pereira Franco Adriano.pdf: 1150244 bytes, checksum: 7217561aaba879ad40863f564c7cc8df (MD5) Previous issue date: 2012-07-30 / Oral manifestations may represent the first clinical signs of HIV infection, being indicators of immunological compromise and of the disease progression. Thus, to investigate these expressions is crucial for the understanding of the epidemiology of AIDS. In this study, it was examined the prevalence of oral manifestations reported in patients with AIDS in the State of Paraíba and its associated factors, according to the Information System for Notifiable Diseases / SINAN, from 2000 to 2010. A quantitative cross-sectional epidemiological study was developed, using secondary data collected from the junction of SINAN W and Net from DST/AIDS program of Paraíba, in patients over 13 years old, who had a complete record of their case evolution. The sample census considered the inclusion criteria previously reported. Statistical analysis covered descriptive and analytical techniques, adopting a confidence interval of 95% and Pearson s chi-squared and prevalence ratio tests . The project was approved by the Ethics Committee of the State University of Paraiba, under CAAE 0404.0.133.000-10.For a total of 2.944 reported AIDS cases, occurred the record of 1009 oral manifestations for this disease, being 76.3% of Oral Candidiasis or Hairy Leukoplakia, 20% of Herpes Zoster and 3.7% of Kaposi's sarcoma. It was demonstrated a significant association between Oral Candidiasis or Hairy Leukoplakia and the variables years of research, macro-regions, years of education and evolution of cases, and it was found in the Herpes Zoster association between the variables years of research, age group and cases development (p <0.05 ). The largest number of oral manifestations identified for AIDS was established in the state capital, João Pessoa. According to the obtained results, the notification of oral manifestations of the disease under study has occurred in less than a half of the confirmed cases. / As manifestações orais podem representar os primeiros sinais clínicos da infecção por HIV, sendo indicadoras de comprometimento imunológico e do tempo de evolução da doença. Assim, investigar essas expressões é fundamental para o entendimento da epidemiologia da AIDS. Neste trabalho verificou-se a prevalência de manifestações orais notificadas em portadores de Aids no Estado da Paraíba e seus fatores associados, de acordo com o Sistema de Informação de Agravos de Notificação / SINAN, durante o período de 2000 a 2010. Desenvolveu-se um estudo epidemiológico transversal e quantitativo, utilizando dados secundários coletados a partir da junção do SINAN W e Net do programa do DST/AIDS da Paraíba, em pacientes maiores de 13 anos, que apresentavam o registro completo da evolução do caso. A amostragem censitária considerou os critérios de inclusão anteriormente relatados. O tratamento estatístico abrangeu técnicas descritivas e analíticas, adotando-se um intervalo de confiança de 95% e os testes Qui-quadrado de Person e Razão de Prevalência. O projeto foi aprovado pelo Comitê de Ética em Pesquisa da Universidade Estadual da Paraíba sob CAAE 0404.0.133.000-10. Para um total de 2944 casos notificados de AIDS ocorreu o registro de 1009 manifestações orais para essa doença, sendo 76,3% de Candidose oral ou Leucoplasia Pilosa, 20% de Herpes Zoster e 3,7% de Sarcoma de Kaposi. Demonstrou-se associação significativa entre a Candidose oral ou Leucoplasia Pilosa e as variáveis ano de investigação, macrorregião,grau de escolaridade e evolução dos casos e para o Herpes Zoster encontrou-se associação entre as variáveis ano de investigação, faixa etária e evolução dos casos (p < 0,05). O maior número de manifestações orais identificadas para a Aids ficou estabelecido na capital do Estado, a cidade de João Pessoa. De acordo com os resultados obtidos a notificação de manifestações orais para a doença em questão ocorreu em menos da metade dos casos confirmados da doença.

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Submitted by Cássio da Cruz Nogueira (cassionogueirakk@gmail.com) on 2017-09-11T18:30:24Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_CaracterizacaoGenotipicaVirus.pdf: 758796 bytes, checksum: b0da38512afba739aff613a2497d7ba3 (MD5) / Approved for entry into archive by Irvana Coutinho (irvana@ufpa.br) on 2017-09-21T14:23:18Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_CaracterizacaoGenotipicaVirus.pdf: 758796 bytes, checksum: b0da38512afba739aff613a2497d7ba3 (MD5) / Made available in DSpace on 2017-09-21T14:23:18Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_CaracterizacaoGenotipicaVirus.pdf: 758796 bytes, checksum: b0da38512afba739aff613a2497d7ba3 (MD5) Previous issue date: 2013 / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / O vírus Varicela-zoster (VVZ) pode causar varicela durante a infecção primária, estabelecendo posteriormente uma infecção latente. Na ocorrência de reativação do vírus, pode surgir o herpes zoster. A análise da presença de anticorpos IgG e IgM é fundamental para verificar a prevalência deste vírus na Região Metropolitana de Belém. O estudo de polimorfismos nucleotídicos específicos é utilizado para definir os genótipos do VVZ. A análise das ORFs 22, 38 e 54 permitiu identificar os genótipos do VVZ de acordo com a classificação estabelecida na conferência de 25 de julho de 2008 em Whitechapel, Londres/Reino Unido, em que as cepas de VVZ detectadas e caracterizadas por sequenciamento dos SNPs foram agrupadas em classes de 1 a 5. Avaliar a prevalência de anticorpos e descrever os genótipos circulantes foi o objetivo deste estudo. A frequência de anticorpos IgG e IgM nos casos de varicela foi 68,2% e 48,2%, respectivamente. Os casos de herpes zoster apresentaram prevalência de anti- VVZ IgG e IgM de 87,5% e 12,5%, respectivamente. Os genótipos 1 ou 3 e 5 estavam presentes nas 13 amostras sequenciadas, sendo que a cepa Européia (classe 1 ou 3) foi encontrada em amostras de todos os municípios estudados. A identificação das cepas VVZ circulantes é de extrema importância em virtude da associação de determinados genótipos a quadros clínicos mais severos e para avaliar a implantação da vacina no Programa Nacional de Imunização. / Varicella zoster virus (VZV) can cause chickenpox during primary infection, subsequently establishing a latent infection. In case of reactivation of the virus, the herpes zoster may occur. Analysis of the presence of IgG and IgM is critical to determine the prevalence of this virus in the Metropolitan Region of Belém. The study of specific nucleotide polymorphisms is used to define the genotypes of VZV. Analysis of ORFs 22, 38 and 54 identified genotypes of VZV according to the classification established in conference July 25, 2008 in Whitechapel, London / UK, where the strains of VZV detected and characterized by sequencing of SNPs were grouped into classes 1 through 5. To evaluate the prevalence of antibodies and describe the circulating genotypes was the aim of this study. The frequency of IgM and IgG antibodies in cases of chickenpox was 68.2% and 48.2%, respectively. Cases of herpes zoster showed prevalence of anti-VZV IgG and IgM of 87.5% and 12.5%, respectively. The genotypes 1 or 3 and 5 were present in 13 samples sequenced, and the European strain (class 1 or 3) was found in samples from all the cities studied. The identification of strains circulating VZV is extremely important because of the association of specific genotypes with clinical harshest and to assess the implementation of the vaccine in the National Immunization Program.

L’infection primaire au VZV et la réactivation du VZV latent sont fréquemment observées à la suite d’une GMO ou d’une GSCO, ce qui cause de sérieuses complications chez le patient. Pour prévenir ces infections, une prophylaxie antivirale est administrée systématiquement chez tous les greffés de MO ou de SCO, alors qu’il n’existe aucun consensus sur la durée optimale d’une telle prophylaxie. Pour résoudre ce problème, notre objectif est de développer et valider une méthode ELISpot-VZV-IFN- qui permettra de suivre la reconstitution de l’immunité à médiation cellulaire anti-VZV chez les receveurs de GMO ou de GSCO et ainsi déterminer le moment opportun pour réduire ou interrompe la prophylaxie chez les receveurs de greffes de CSH. Dans un premier temps, des valeurs-seuil de la réponse à médiation cellulaire anti-VZV chez la population pédiatrique saine ont dû être générées. À la lumière de nos résultats, un enfant avec un résultat ELISpot-VZV-IFN- > 190.0 SFU/106 PBMC devrait être protégé contre une possible infection à VZV. Pour valider cette étude, une étude prospective de la reconstitution immunitaire anti-VZV a été effectuée chez 9 enfants greffés de MO ou de SCO. Nos résultats préliminaires ont montré qu’il n’y avait eu aucune reconstitution significative de l’immunité à médiation cellulaire anti-VZV dans les 18 premiers mois post-transplantation chez 8 de ces 9 enfants. Les résultats de ces expériences vont fournir d’importantes informations quant à la reconstitution de l’immunité anti-VZV à la suite d’une GMO ou d’une GSCO et pourraient permettre l’amélioration des soins apportés aux receveurs de GMO ou de GSCO. / Primary infection with VZV and reactivation of latent VZV are commonly observed following BMT and UCBT, leading to serious complications in patients. As a result, antiviral prophylaxis is systematically administered to BMT and UCBT recipients, yet there is no consensus that defines its optimal duration. To resolve this problem, our objective was to develop and validate a VZV-IFN--ELISpot with which reconstitution of VZV immunity can be followed in BMT and UCBT recipients, providing clinicians a practical tool to gauge the need for and adjust antiviral prophylaxis in individual HSCT recipients. First of all, threshold values for anti-VZV immunity in healthy pediatric subjects were generated. Based on our results, a child exhibiting > 190.0 VZV-specific SFU /106 PBMC should be protected against a possible VZV infection. To validate these results, a prospective study on the recovery of VZV-specific T cell immunity was performed on 9 children following BMT or UCBT. Preliminary results demonstrated that there was no significant recovery of VZV-specific T cell immunity in the first 18 months post-transplantation in 8 of 9 cases. Results of these experiments will yield important new information regarding reconstitution of anti-VZV immunity following BMT and UCBT and could lead to improvements in clinical management of BMT and UCBT recipients.

L’infection primaire au VZV et la réactivation du VZV latent sont fréquemment observées à la suite d’une GMO ou d’une GSCO, ce qui cause de sérieuses complications chez le patient. Pour prévenir ces infections, une prophylaxie antivirale est administrée systématiquement chez tous les greffés de MO ou de SCO, alors qu’il n’existe aucun consensus sur la durée optimale d’une telle prophylaxie. Pour résoudre ce problème, notre objectif est de développer et valider une méthode ELISpot-VZV-IFN- qui permettra de suivre la reconstitution de l’immunité à médiation cellulaire anti-VZV chez les receveurs de GMO ou de GSCO et ainsi déterminer le moment opportun pour réduire ou interrompe la prophylaxie chez les receveurs de greffes de CSH. Dans un premier temps, des valeurs-seuil de la réponse à médiation cellulaire anti-VZV chez la population pédiatrique saine ont dû être générées. À la lumière de nos résultats, un enfant avec un résultat ELISpot-VZV-IFN- > 190.0 SFU/106 PBMC devrait être protégé contre une possible infection à VZV. Pour valider cette étude, une étude prospective de la reconstitution immunitaire anti-VZV a été effectuée chez 9 enfants greffés de MO ou de SCO. Nos résultats préliminaires ont montré qu’il n’y avait eu aucune reconstitution significative de l’immunité à médiation cellulaire anti-VZV dans les 18 premiers mois post-transplantation chez 8 de ces 9 enfants. Les résultats de ces expériences vont fournir d’importantes informations quant à la reconstitution de l’immunité anti-VZV à la suite d’une GMO ou d’une GSCO et pourraient permettre l’amélioration des soins apportés aux receveurs de GMO ou de GSCO. / Primary infection with VZV and reactivation of latent VZV are commonly observed following BMT and UCBT, leading to serious complications in patients. As a result, antiviral prophylaxis is systematically administered to BMT and UCBT recipients, yet there is no consensus that defines its optimal duration. To resolve this problem, our objective was to develop and validate a VZV-IFN--ELISpot with which reconstitution of VZV immunity can be followed in BMT and UCBT recipients, providing clinicians a practical tool to gauge the need for and adjust antiviral prophylaxis in individual HSCT recipients. First of all, threshold values for anti-VZV immunity in healthy pediatric subjects were generated. Based on our results, a child exhibiting > 190.0 VZV-specific SFU /106 PBMC should be protected against a possible VZV infection. To validate these results, a prospective study on the recovery of VZV-specific T cell immunity was performed on 9 children following BMT or UCBT. Preliminary results demonstrated that there was no significant recovery of VZV-specific T cell immunity in the first 18 months post-transplantation in 8 of 9 cases. Results of these experiments will yield important new information regarding reconstitution of anti-VZV immunity following BMT and UCBT and could lead to improvements in clinical management of BMT and UCBT recipients.

Background: The prevalence of herpes zoster (HZ) is high in patients with rheumatic diseases. Systemic lupus erythematosus (SLE) doubles the risk for developing HZ. However, little is known about natural humoral immunity against varicella zoster virus (VZV) in patients with SLE. Hence, we compared VZV IgG antibody concentrations in a group of SLE patients with healthy controls and patients with rheumatoid arthritis (RA). Methods: n = 56 patients with SLE, n = 54 patients with RA, and n = 56 healthy controls were included in this study. The VZV IgG antibody concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The antibody concentrations were compared between the groups. Results: Overall IgG antibody titers for VZV in SLE patients were comparable to healthy controls but higher when compared to patients with rheumatoid arthritis (p = 0.0012). In consequence, antibody levels in controls were higher than in RA patients (p = 0.0097). Stratification by age revealed highest titers among SLE patients in the fourth life decade (p = 0.03 for controls, p = 0.0008 for RA patients) whereas RA patients in their sixth decade had the lowest antibody concentration (p = 0.03 for controls, p = 0.04 for SLE patients). Regarding the individual HZ history, antibody levels of SLE patients with a positive history exceeded all other groups. Conclusions: Although humoral VZV immunity in SLE patients is comparable to healthy controls it seems to be pronounced in young SLE patients between 30 and 39. The lowest VZV IgG levels were found in RA patients. HZ seems to induce antibody production, particularly in patients with SLE. Immunological processes might contribute to VZV antibody levels in SLE patients, but further investigations are needed to substantiate this hypothesis. Even though the increased HZ prevalence seems to be independent of humoral immunity in SLE patients, reduced humoral immunity might contribute to HZ in RA patients. The available HZ subunit vaccination might be an appropriate way to reduce the HZ risk in patients with rheumatic diseases.